Pavlovian SocietyAnnual Meeting, 2015

Portland Hilton

Sept 17–19, 2015

OverviewAll events will be located in the Skyline Level (23rd Floor)

Thur 6:00–10:00 PM Opening ReceptionHors d’Oeuvres & Cash Bar

Fri 7:30–8:25 Breakfast8:25–11:40 Morning Sessions12:10–1:50 Lunch

(Exec Committee Meeting)1:50–5:00 Afternoon Sessions5:30–7:30 Posters & Cash Bar

Sat 7:30–8:30 Breakfast8:30–Noon Morning SessionsNoon–1:30 Lunch

(WIL Luncheon)1:30–5:00 Afternoon Sessions

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5:30–7:30 Posters & Cash Bar7:30–9:00 Banquet

Program

Friday (Sept 18)7:30–8:25 Breakfast8:25–8:30 Welcome: Matt Lattal (OHSU)8:30–10:10 Symposium: TheOntogeny of Cognition

during Adolescence: Behavior and Neu-robiologyDavid J. Bucci & Mark E. Stanton, Chairs

8:30–8:55 Mark Stanton (U Delaware): The ontogenyof learning in context

8:55–9:20 Siobhan Pattwell (Fred Hutchinson Can-cer Research Center): Leveraging Dy-namic Changes in Neural Circuitry DuringAdolescence to Persistently Attenuate FearMemories

9:20–9:45 Heidi Meyer (Dartmouth): Behavioral andNeurobiological Substrates of Negative Oc-casion Setting During Adolescence

9:45–10:10 Jill A. McGaughy (U New Hampshire):Do changes in Prefrontal NorepinephrineTransporter density across Adolescence in-fluence the Development of Cognitive Con-trol in rats?

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10:10–10:30 Coffee Break10:30–12:10 Symposium: Drugs and Conditioning

Chris Cunningham (OHSU), Chair10:30–10:55 Barbara Sorg (Washington State): Role

of Perineuronal Nets in Cocaine-AssociatedMemory

10:55–11:20 Rick Bevins (U Nebraska): ConditionedEnhancement of the Nicotine Reinforcer

11:20–11:45 Linda Parker (U Guelph): Endocannabi-noid Regulation of Nausea is mediated by2-Arachidonoylglycerol (2-AG) in the RatVisceral Insular Cortex

11:45–12:10 Chris Cunningham (OHSU): Deconstruct-ing the Elements of Context in PavlovianDrug Conditioning

12:10–1:50 Lunch (on your own) and Executive Com-mittee Meeting

1:50–2:20 Karyn Frick (U Wisconsin-Milwaukee)Neural Mechanisms Through Which Pro-gesterone Regulates Hippocampal Mem-ory

2:20–3:10 Jeansok J. Kim (U Washington)Place and Time of Fear

3:10–3:30 Coffee Break3:30–5:00 Symposium: Remembering the contri-

butions of Richard F. ThompsonParticipants include:James McGaugh (UCI), chair

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Tracey Shors (Rutgers)Ted Berger (USC)Joseph Matarazzo (OHSU)

5:30–7:30 Posters and Cash Bar

Saturday (Sept 19)8:30–10:30 Symposium: Remembering the Contribu-

tions of Nicholas MackintoshPeter Balsam (Columbia), ChairRalphMiller (SUNYBinghamton): The Con-struct of Attention and Beyond: Homage toNJ MackintoshGavan P. McNally (UNSW Australia): Se-lecting Danger Signals: Attention, CS Asso-ciability, and Fear Learning.Guillem Esber (CUNY, Brooklyn College):Reconciling the Effects of Predictivenessand Uncertainty on Attention in AssociativeLearningVictoria Chamizo (University of Barcelona):Trying to Understand the Differential Use ofSpatial Information in Male and Female Ratsof Different Age, Juveniles and Adults.

10:30–10:40 Break10:40–11:05 Melissa Sharpe (Princeton/NIDA): The Pre-

limbic Cortex Directs Attention Toward Pre-dictive Cues During Pavlovian Conditioning

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11:05–11:30 Melissa Malvaez (UCLA): Histone Acetyla-tion in the Dorsolateral Striatum SelectivelyMediates the Formation of Behavioral Habits

11:30–11:55 Mark Baxter (Mt. Sinai): Cognitive andSocioemotional Development After Postna-tal Anesthetic Exposure

12:00–1:30 Lunch — Women in Learning satellite meet-ing at the Picnic HouseSee last page of Program

1:30–3:10 Symposium: Neuroimmune and Neu-roendocrine Modulation of MemoryNatalie Tronson (U Michigan), Chair

1:30–1:55 Ruth Barrientos (Colorado): Neuroinflam-mation in the Normal Aging Hippocampus:Causes, Effects, and Therapeutic Interven-tions

1:55–2:20 John F. Guzowski (UCI): Cytokine modula-tion of hippocampal circuit activity and mem-ory function

2:20–2:45 Natalie Tronson (U Michigan): PersistentMemory Deficits and Histone Modificationsafter a Systemic Inflammatory Event

2:45–3:10 Andrey Ryabinin (OHSU): Mice transfer in-creased pain sensitivity via olfactory cues

3:10–3:30 Break3:30–5:10 Symposium — Retrieval and Extinction

Processes

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Tom Gould (Temple), Chair3:30–3:55 Brian Wiltgen (UC Davis): Retrieving mem-

ory with the hippocampus3:55–4:20 Martha Escobar (Oakland U.): Synaptic

Plasticity Changes After Retrieval of Contex-tual Fear Memories

4:20–4:45 Michael Drew (U. Texas): Dentate GyrusControls Extinction of Contextual Fear Mem-ory

4:45–5:10 Dayan Knox (U. Delaware): Examining theeffects of stress on fear extinction using thesingle prolonged stress paradigm

5:30–7:30 Posters and Cash Bar7:30–9:00 Banquet

Speaker: Steve Sylvester (WashingtonState): Oysters, Invaders, Sex and CO2Awards

1 PostersGenerally alphabetical by author except for some moved be-tween days.

Posters whose first author’s last name begins with A–H will be presented at Friday’s Poster Session.

1 Pina, Melanie M.; Cunningham, Christopher L. (Ore-gon Health & Science University) Ethanol-Seeking Behavioris Expressed Directly through an Extended Amygdala to Mid-brain Neural Circuit

2 Abraham, Antony; Land, Benjamin; Soltys, David;Chavkin, Charles (University of Washington) Kappa Opioid

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Receptor Activation Disrupts Behavioral Inhibition in Schedule-Controlled Tasks

3 Adkins, Jordan ; Webster, Natalia; Lynch, Joseph III;Vanderhoof, Tyler, T. Gilman, Lee, Jasnow, Aaron (KentState University ) Influence of GABAB1 Receptor Deletion inCorticotropin Releasing Factor Neurons on Fear, Anxiety, andSocial Stress

4 Allen, Todd; Miller, Daniel; Williams; David; West,Kaitlyn; Servatius, Richard, (University of Northern Colorado;Stress and Motivated Behavior Institute; Carthage College)US Alone Trials Are DisruptiveWhen Pre-Exposed Prior to CS-US training, but not when Interpolated into CS-US Training.

5 Asok, Arun; Draper, Adam; Schulkin, Jay; Rosen,Jeffrey B. (University of Delaware) Optogenetically Dissect-ing the Function of Corticotropin-Releasing-Factor NeuronsDur-ing Contextual Fear Learning

6 Blacktop, Jordan M; Churchill, Lynn; Todd, Ryan P;Slaker, Megan; Sorg, Barbara A. (Washington State Univer-sity, Vancouver) Role of Anterior Dorsal Lateral HypothalamicArea Perineuronal Nets in the Acquisition of Cocaine-InducedConditioned Place Preference

7 Calub, Catrina; Furtak, Sharon; Brown, Thomas (Cal-ifornia State University, Sacramento; Yale University) Auto-conditioning Hypothesis for Acquired Fear of Ultrasonic AlarmCries

8 Campese, D. Vinn; Kim, T. Ian; LeDoux, E. Joseph(New York University) Different forms of conditioned motiva-tion depend on different regions in the amygdala

9 Collins, Sean; Chau, Lily; Galvez, Roberto (Universityof Illinois Urbana-Champaign) Associative learning temporar-ily increases SHANK neocortical expression consistent withanatomical plasticity

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10 Czerniawski, Jennifer; Guzowski, John F (Universityof California - Irvine) Minocycline Treatment Blocks Cytokine-Induced Alterations in Hippocampal Circuit Activity and Con-text Discrimination Memory Impairment.

11Daniels, W. Carter ; Sanabria, Federico (Arizona StateUniversity) The Effect of Chronic Nicotine Administration onSign- and Goal-Tracking: A Pilot Study

12 de Solis, Christopher; Holehonnur, Roopa; Baner-jee, Anwesha; Luong, Jonathan, Lella Srihari; Ho, Anthony;Pahlavan, Bahram; Ploski, Jonathan (University of Texas atDallas) Viral Delivery of shRNA to Amygdala Neurons Leadsto Neurotoxicity and Deficits in Pavlovian Fear Conditioning

13 Elkin, Magdalyn E.; Freeman, John H. (University ofIowa) Ontogenetic Changes In Anterior Cingulate CorticalActivity during Trace Eyeblink Conditioning.

14 Farley, Sean; Freeman, John (The University of Iowa)Cerebellar Feedback is Necessary for Learning Related Ac-tivity in the Medial Auditory Thalamic Nuclei During EyeblinkConditioning

15 Furtak, Sharon; Calub, Catrina; Potter, Nicole (Cal-ifornia State University, Sacramento) Perirhinal Cortex In-volvement in Fear Extinction to a Discontinuous Visual Stimu-lus

16 Gahtan, Ethan; Bishop, Benjamin (Humboldrt StateUniversity) Light-Evoked Diving Reflex In Zebrafish Larvae

17 Garr, Eric; Delamater, Andrew R. (Graduate Centerof the City University of New York; Brooklyn College) ActionSequences are Sensitive to Reward Devaluation

18 Gonzalez, Sarah T.; Fanselow, Michael S. (Universityof California, Los Angeles) The Neural Mechanisms of SafetyLearning in Mice

19 Goode, Travis; Jin, Jingji; Holehonnur, Roopashri;

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Ploski, Jonathan; Maren, Stephen (Texas A&M University)Combinatorial DREADDSilencing of Ventral Hippocampal Neu-rons Projecting to Infralimbic Cortex Prevents Fear Renewal

20 Goosens, Ki; Barbara Gisabella, Junmei Yao (Mas-sachusetts Institute of Technology) Enhanced Growth Hor-mone in Amygdala Neurons Dysregulates Associative FearMemory Allocation

21 Gould, Thomas (Temple University) Adolescent Nico-tine Exposure Alters Adult Contextual Fear Conditioning

22Gray, Michael S.; Lynch III, Joseph F;Winiecki, PatrickiA.; Jasnow, Aaron M. (Kent State University) Presynap-tic GABAB(1a) Receptors Preserve Context Memory DuringConsolidation

23Hafenbreidel, Madalyn; Rafa Todd, Carolynn; Smies,Chad. W.; Twining, Robert C.; Mueller, Devin (University ofWisconsin, Milwaukee) Blocking Infralimbic Basic FibroblastGrowth Factor (bFGF or FGF2) Facilitates Extinction of DrugSeeking

24Hanson, Erica E., Mitchell, SuzanneH. (Oregon Health& Science University) Fos expression after exposure to an ef-fort discounting procedure

25 Heroux, Nicholas; Robinson-Drummer, Patrese A.;Rosen, Jeffrey B.; Stanton, Mark E. (University of Delaware)Role of NMDA Receptors in the Acquisition and Retention ofthe CPFE in Adolescent Rats

26Hersman, Sarah; Hoffman, Annie; Hodgins, Lili; Shieh,Shannon; Lam, Jamie; Fanselow, Michael S (UCLA) Dis-sociation of Cholinergic Modulation in Dorsal Hippocampusand Basolateral Amygdala on Stress-enhanced Fear Learning

27 Huckleberry, Kylie A.; Ferguson, Laura B.; Drew,Michael R. (University of Texas at Austin) Behavioral Mech-anisms of Context Fear Generalization

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28 Huda, K. Rebecca; Latsko, Maeson S; Gilman, LeeT; Jasnow, Aaron M. (Kent State University) Resistance toSocial Defeat Stress is Characterized by Poor Behavioral In-hibition; Assessment in Passive Avoidance

29 Hui, May; Zelikowsky, Moriel; Anderson, David (Cal-ifornia Institute of Technology) Tac2 mediates chronic stressin mice

The following posters (first author’s last name beginswith J–W) will be presented at Saturday’s Poster Session.

1 Alfiler, Lauren K. & Pribic, Micaela R.; Rose, Jacque-line K. (Western Washington University) Deletion of CaMKIIγin C. elegans Results in an Associative Conditioning DeficitWithout Affecting Mobility, Defecation or Fecundity.

2 Johnson, Brandon. A.; Wilson, W. Jeffrey (Albion Col-lege) Light-induced Attenuation of Response to Light in theEarthworm Lumbricus terrestris

3 Kennedy, Bruce C; Kohli, Maulika; Maertens, Jamie;Marell, Paulina; Gewirtz, JonathanC (University of Minnesota)Conditioned Object Preference: A Novel Measure of Drug-Seeking in Rodents

4 Kim, Earnest; Lattal, Matthew K. (Oregon Health & Sci-ence University) Amygdala Modulation of Cocaine-seekingBehavior

5 Knox, Dayan; Stanfield, Briana R; Staib, Jennifer;Keller, SamanthaM;DePietro, Thomas. (University of Delaware)Using Measures of c-Jun Activity to Determine Mnemonic Pro-cesses Through which SPS Exposure Disrupts Extinction Re-tention

6 Koraym, Adam; Gallimore, Darci; Kidd, Tara; Dodd,Maria; Hennessy, Michael B.; Claflin, Dragana I. (WrightState University) Effects of Early-Life Stress and Social Buffer-

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ing on Learning in Juvenile Rats7 Kwapis, Janine L.; Alaghband, Yasaman; Kramar,

Eniko A.; Matheos, Dina P.; Rhee, Diane; Lopez, Alberto,J.; Wood, Marcelo A. (University of California, Irvine) HDAC3:An Epigenetic Key to Ameliorating Synaptic Plasticity andMem-ory Deficits in the Aging Brain

8 Lacagnina, Anthony F; Drew, Michael R (Universityof Texas at Austin) Enhanced Context Fear Memory withSpaced Context Exposures

9 Latsko, Maeson S.; Farnbauch, Laure A.; Jasnow,AaronM. (Kent State University) Enhanced juvenile glucocor-ticoid response is associated with an adult resistant phenotypefollowing juvenile social defeat

10 Laude, R. Jennifer; Fillmore, T. Mark (University ofKentucky) Activities Engaged in While Drinking Affect Per-ceived Intoxication and Craving for Alcohol

11 Lee, Ji-Hye; Kimm, Sunwhi; Choi, June-Seek (KoreaUniversity) Effect of Emotional Trauma during Adolescenceon subsequent Aversive Memory Formation in rats

12 Lee, Yeon Kyung; Hong, Eun-Hwa; Kim, Sunwhi;Jie, Hyesoo; Choi, June-Seek Choi (Korea University) Un-controllable stress effects on discriminatory avoidance learn-ing

13 Loh, Ryan; Galvez, Roberto (University of Illinois atUrbana-Champaign) Neocortical Kappa Inhibition AttenuatesForebrain-Dependent Associative Learning

14 Lynch III, Joseph; Gray, Michael; Ouellette, Emily;Adkins, Jordan; Winiecki, Patrick A.; Riccio, David C.;Jasnow, AaronM.; (Kent State University) Estradiol-inducedFear Generalization is Blocked by Inactivation of NMDA orAMPA Receptors Prior to Retrieval

15 Murawski, Nathen J.; Asok, Arun (Center for Neu-

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roscience, UC Davis (NJM); Department of Psychology andBrain Sciences, University of Delaware (AA)) Digital ContextFear Conditioning in Rats: Utilizing LCD-Based Visual ContextManipulations During Conditioning

16 Noble, J. Lindsey; Gonzalez, Ian J; Ngo, Tiffany T,Malhotra, Simran; Meyers, Eric; Bleker, Nathaniel, Car-rillo, D’angelique D; Ramananthan, Karthik R; Rennaker,Robert L; Kilgard, Michael P; McIntyre, Christa K* (TheUniversity of Texas at Dallas) Vagus Nerve Stimulation En-hances Extinction of Conditioned Fear in an Animal Model ofPTSD

17 Ouellette, B. Emily; Lynch III, F. Joseph; Riccio, C.David; McEwen, S. Bruce; Jasnow, M. Aaron (Kent StateUniversity) Corticosterone Attenuates Context Fear General-ization in Male Rats

18 Pennington, Zachary T.; Avershal, Jacob Z.; Ander-son, Austin S.; Fanselow, Michael S. (University of Califor-nia, Los Angeles) Broadening the stress enhanced fear learn-ing (SEFL) model: acute shock exposure augments subse-quent startle responses and contextual fear of a startle-pairedcontext

19 Pisansky, Marc T.; Gewirtz, Jonathan C. (Universityof Minnesota - Twin Cities) Intranasal oxytocin enhances so-cially transmitted fear behavior in mice

20 Pizzimenti, Christie; Lattal, K.Matthew (Oregon Health& Science University) Context-independent effects of shockon drug-seeking

21 Pochiro, JosephM;Goodfellow, Molly J; Lee, MichaelA; Lindquist, Derick H. (The Ohio State University) TraceFear Conditioning and Hippocampal NR2B-NMDA ReceptorSignaling in Adult Rats Administered Ethanol During the ThirdTrimester-equivalent Period

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22 Rafa Todd, Carolynn; Hafenbreidel, Madalyn; Otis,James, M.; Twining, Robert, C.; Mueller, Devin (Universityof Wisconsin, Milwaukee) Infralimbic NR2A-containing NMDAReceptors are Necessary for the Reconsolidation of CocaineSelf-administration Memory

23 Rankin, Catharine H.; Giles, A.C., Ardiel, E. A., Yu,A. (University of British Columbi) Response Based Analysesof Behavior Overlook Other Important Behavioral Changes:Integrating Habituation into Ongoing Behavior

24 Reyes, Kyrie-Anne E.; Kudva, Priya S; Todd, RyanP; Sorg, Barbara A. (Washington State University) Prazosindisrupts reconsolidation of appetitive and aversive behavior inrats: discordance between behavior and ultrasonic vocaliza-tions

25 Robinson-Drummer, Patrese; Heroux, Nicholas A.;Stanton, Mark E. (University of Delaware) Intra-dorsal Hip-pocampal antagonism of Muscarinic Acetylcholine receptorsdisrupts the Context Preexposure Facilitation Effect

26 Rose, Jacqueline; Alfiler, Lauren K.; Pribic, MicaelaR. (Western Washington University) Pavlovian ConditioningProduced by Activating Two Identified and Distinct Neural Cir-cuits in C. elegans

27 Sangha, Susan (Purdue University) Amygdalocorti-cal Circuitry Contributes to Discriminative Reward, Fear andSafety Learning

28 Shipman, Megan L.; Trask, Sydney; Green, John T.;Bouton, Mark, E. (The University of Vermont) Inactivationof the Prelimbic Cortex Attenuates Context-Dependent Exci-tatory Operant Responding

29 Shors, Tracey J. ; Olson, Ryan; Brush, ChristopherJ.; Alderman, Brandon (Rutgers University) Mental andPhysical (MAP) Training: Combining Meditation and Aerobic

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Exercise Enhances Synchronized Brain Responses during Con-flict Monitoring

30 Slaker, Megan; Sorg, Barbara A. (Washington StateUniversity) Perineuronal nets in the prefrontal cortex con-tribute to acquisition of drug-associated memory

31 Trask, Sydney; Bouton, Mark A., Carranza-Jasso,R. (The University of Vermont) Learning Not to Make the Re-sponse During Operant Extinction

32Williams, AmyR.; Lattal, K. Matthew (OHSU) Effectsof Acute Ethanol Withdrawal on Extinction and Reconditioningof Fear

Poster AbstractsAlphabetical by first author.

Abraham, Antony; Land, Benjamin; Soltys, David; Chavkin,Charles (University of Washington) Kappa Opioid ReceptorActivation Disrupts Behavioral Inhibition in Schedule-ControlledTasks. Dysregulation of the dynorphin/kappa opioid recep-tor (KOR) system has been implicated in the pathologies ob-served in substance use disorders and affective disorders. Inhumans, pharmacological KORactivation is hallucinogenic anddisrupts cognition. A fundamental component of cognitive tasksis the development and maintenance of temporal associationsbetween stimuli to properly guide responding. To measure dis-ruptions in temporal processing and behavioral inhibition in-duced by KOR activation, male C57Bl/6 mice were trained ina differential reinforcement of low rates of responding (DRL)task for food reward. In the DRL task, mice were required towithhold responding during an unsignaled, fixed time period(15s) following a reinforced response. Optimal responses in

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the DRL task required interresponse times (IRT) greater than15s, and premature or ’incorrect’ responses in the DRL taskled to reset of the 15s wait period. Mice were tested in theDRL task with U50,488 (a prototypical KOR agonist), Salvi-norin A (a recreationally used KOR agonist), or following re-peated forced swim stress with or without norBNI (a kappa an-tagonist). Repeated forced swim stress significantly increasedthe percentage of incorrect responses in the DRL task and thiseffect was blocked by KOR antagonism. KOR activation withU50,488 and Salvinorin A also significantly increased the per-centage of incorrect responses in the DRL task. These resultsdemonstrate that KOR activation, via stress or pharmacologi-cal treatment, disrupts performance in the DRL task. These ef-fects are hypothesized to be specific to inhibitory control of re-sponding, rather than time estimation, as most errors occurredin bursts of responding at the beginning of wait period. De-creased behavioral inhibition has been proposed as a mecha-nism underlying substance abuse disorders, and the presentstudy indicates these cognitive disruptions may be KOR medi-ated. Future studies will further specify the cellular and neuralsubstrates involved in KOR-mediated disruptions in cognition.SUPPORT: T32DA07278 (AA), KO5DA02570 (CC), NARSADYoung Investigator Award (BBL), and P50MH106428 (CC)

Adkins, Jordan ; Webster, Natalia; Lynch, Joseph III;Vanderhoof, Tyler, T. Gilman, Lee, Jasnow, Aaron (KentState University ) Influence of GABAB1 Receptor Deletion inCorticotropin Releasing Factor Neurons on Fear, Anxiety, andSocial Stress. Corticotropin releasing factor (CRF) is highlyexpressed in the paraventricular nucleus (PVN) and through-out the brain, and plays a critical role in neuroendocrine andbehavioral responses to stress. Yet how the CRF system ismodulated to elicit such responses remains unclear. Previ-

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ous research in our lab demonstrated CRF-specific disruptionof NMDA receptor function sex-dependently enhanced fear,sociability, and social stress responsivity. Furthermore, CRF-specific deletion of GABAAÎś1 subunits also enhanced anxietyand disrupted fear extinction. As a way to further explore theglutamatergic and GABA-ergic regulation of the CRF system,we utilized a floxed GABAB1 transgenic mouse crossed with aCRF-Cre driven mouse, allowing specific GABAB1 deletion inCRF-expressing neurons. CRF GABAB1 knockout mice weretrained in context and cued fear conditioning, assessed in anx-iety measures, and underwent social defeat to examine socialstress sensitivity. Based on our previous findings, we hypoth-esized CRF-GABAB1 knockout mice would show increasedfear and anxiety responses. However, CRFGABAB1 knockoutmales, but not females, displayed reduced context and cuedfear compared to wildtype littermates. CRF-specific deletionof GABAB1 receptors had no effect on anxiety-like behavior inmales or females. Additionally, female knockout mice, but notmales, trended towards spending less time in the closed armsof the elevated maze plus, suggesting less anxiety-like behav-ior. Finally, after experiencing social defat, no differences wereobserved between the two genotypes in a social interactiontest. Theses data demonstrate sex-specific effects of GABAB1receptor deletion within CRF neurons on fear, anxiety-like be-havior and social stress responsivity. Contrary to our hypothe-sis, CRF-GABAB1 knockouts displayed decreased fear to bothcontext and cue, but no differences in anxiety-like behavior orsocial stress responsivity. Our findings indicate GABAB1- me-diated GABA-ergic regulation of CRF neurons is important forappropriately regulating fear, likely functioning to promote sur-vival under specific aversive circumstances.

Alfiler, Lauren K. & Pribic, Micaela R.; Rose, Jacque-

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line K. (Western Washington University) Deletion of CaMKIIγin C. elegans Results in an Associative Conditioning DeficitWithout AffectingMobility, Defecation or Fecundity. . Calcium/calmodulin-kinase II (CaMKII) modulates themechanisms of neuronal plas-ticity that underlie learning. Recently, CaMKIIγ has been shownto act as a nuclear transporter, mobilizing from the postsynap-tic density to the nucleus to activate gene transcription in re-sponse to neuronal firing (Ma et al., 2014). In C. elegans, theCaMKII mutant strain unc-43(gk452) carries a specific dele-tion for the UNC-43T isoform, a putative ortholog of humanCaMKIIγ , for which there is no published phenotype. Our labhas observed several behaviors and have found no imme-diately obvious phenotypes of this mutation: unc-43(gk452)worms show normal egg-laying, defection and general mobil-ity. Further investigation revealed that unlike wild-type, unc-43(gk452) worms were unable to demonstrate avoidance toNaCl following pairing of that stimulus with starvation. In addi-tion, unc-43(gk452) worms show a deficit for associative con-ditioning resulting from aClassical Conditioning protocol. Wild-type worms show an increased avoidance response when amechanosensory stimulus (NS, vibratory low frequency tone)is paired with a UV or blue-wavelength light stimulus (US).However, unc-43(gk452) worms exhibit either no change inresponse or a decrease in response to the mechanosensorystimulus alone, thus suggesting no influence of the US. Theseresults suggest that CaMKIIγ may be a necessary componentfor associative conditioning. Current work includes identifyingnecessary coding regions of the UNC-43T isoform by gener-ating transgenic rescues and examining behavior.

Allen, Todd; Miller, Daniel; Williams; David; West, Kait-lyn; Servatius, Richard, (University of Northern Colorado;Stress and Motivated Behavior Institute; Carthage College)

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USAlone Trials Are DisruptiveWhen Pre-Exposed Prior to CS-US training, but not when Interpolated into CS-US Training.. Recent work has indicated a differential effect of US alonetrials on classical eyeblink conditioning dependent on whenthese trials are presented in training. Holloway et al. (2012)reported enhanced proactive interference of eyeblink condi-tioning following US alone pre-exposures in individuals withhigh trait anxiety. More recently, acquisition of CRs did not dif-fer between partial reinforcement with 50% US alone (cornealair puff) trials as compared to 100%CS-US (tone-air puff) trials(Allen et al., 2014). A review of the literature revealed that Kim-ble et al. (1955) tested a protocol with an interpolated block of20 US alone trials during CS-US training which did not disruptCRs. We sought to extend the work with US alone trainingboth when pre-exposed and interpolated with anxiety vulner-ability individuals. Undergraduates completed personality in-ventories including the Adult Measure of Behavioural Inhibition(AMBI). All participants received 60 acquisition trials. Acquisi-tion consisted of either 100% CS-US training, 20 CS-US trialsfollowed by 20 US alone trials, followed by 20 more CS-US tri-als or 30 US alone pre-exposures followed by 30 CS-US trials.The US alone pre-exposures disrupted acquisition of eyeblinkCRs which replicated the findings of Holloway et al. In addi-tion, US alone pre-exposures eliminated the enhanced acqui-sition normally observed in BI individuals. The interpolated USalone trials did not disrupt CRs. BI individuals exhibited moreCRs than non-inhibited individuals in the 100%CS-US trainingprotocol and the Kimble et al. protocol. It appears that BI indi-viduals are not affected by US alone trials once CR acquisitionhas begun to the US, but are severely disrupted by US alonepre-exposure prior to CS-US training. Our findings will be dis-cussed in the light of the neural substrates of eyeblink condi-

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tioning as well as possible factors such as hypervigilance, cuesalience and learned helplessness. SUPPORT: University ofNorthern Colorado Professional Development Funds and theStress and Motivated Behavior Institute

Asok, Arun; Draper, Adam; Schulkin, Jay; Rosen, Jef-frey B. (University of Delaware) Optogenetically Dissectingthe Function of Corticotropin-Releasing-Factor Neurons Dur-ing Contextual Fear Learning. For almost two decades, it hasbeen hypothesized that a corticotropin-releasing-factor (CRF)pathway from the central nucleus of the amygdala (CeA) tothe bed nucleus of the stria terminalis (BNST) controls fear tosustained threats. However, the function of CRF in this path-way has remained elusive because of technological limitationsof selectively inhibiting or activating CRF neurons. Thus, inthe present study, we sought to investigate this CRF path-way by using a cell-type specific optogenetic approach dur-ing contextual fear conditioning. First, we developed a plas-mid containing archaerhodopsin tp009 (ArchT) fused to en-hanced green fluorescent protein (EGFP) flanked by a CRFpromoter (CRF-ArchT-EGFP) and packaged it into a serotype-2 adeno-associated virus (AAV2). Immunohistochemical co-labeling with a CRF antibody following viral transfection withAAV2-CRF-ArchT-EGFP showed highly selective expressionof the construct in CRF-positive cells. Second, the AAV2-CRF-ArchT-EGFP was injected into the CeA of rats and then fiberoptic cannula were bilaterally implanted above the CeA. Fourweeks after virus injection, we selectively inhibited CeA CRFneurons with green laser light during contextual fear condi-tioning. We found inhibition of CRF neurons in the CeA re-duced freezing during multi-trial contextual fear conditioning(5 shocks presented 3 minutes apart). Furthermore, freezingremained low during a light-free retention test 24 hours later.

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This disruption in freezing was not due to rats’ inability to re-spond to the shock during optogenetic inhibition. These stud-ies highlight an important role for CRF neurons in the CeAduring contextual fear learning. Ongoing work will examinethe effects of optogenetic inhibition of CeA CRF projectionsto the BNST during contextual fear conditioning. SUPPORT:R01HD075066

Blacktop, Jordan M; Churchill, Lynn; Todd, Ryan P;Slaker, Megan; Sorg, Barbara A. (Washington State Univer-sity, Vancouver) Role of Anterior Dorsal Lateral HypothalamicArea Perineuronal Nets in the Acquisition of Cocaine-InducedConditioned Place Preference. Addiction involves drug-inducedneuroplasticity of the circuitry of motivated behavior, which in-cludes the medial forebrain bundle and the lateral hypothala-mic area. Emerging at the forefront of neuroplasticity regu-lation are specialized extracellular matrix structures that formperineuronal nets (PNNs) around certain neurons, mainly par-valbumin positive (PV+) fast-spiking interneurons (FSINs), mak-ing them a promising target for the regulation of drug-inducedneuroplasticity. Despite the emerging significance of PNNs indrug-induced neuroplasticity and the well-established role ofthe lateral hypothalamic area (LHA) in reward/reinforcement/motivation,very little is known about how PNN-expressing neurons con-trol drug-seeking behavior. The goals of this experiment were:1) to determine areas of high PNN expression within the LHA,and 2) whether PNN expression within the LHA is necessaryfor cocaine-induced conditioned place preference (CPP). Adiscrete region of the anterior dorsal LHA (LHAad) was foundto exhibit robust PNN expression, while the rest of LHA ex-hibited comparatively sparse PNN expression. Compellingly,only PNN removal via chrondroitinase ABC (Ch-ABC) admin-istration within the dorsal anterior LHA prior to conditioning

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abolished acquisition of cocaine-induced CPP, highlighting theimportance and specificity of PNN removal within this subre-gion of the LHA. It was determined that approximately 87%of LHAad WFA positive neurons are PV+. Removal of LHAadPNNs did not affect locomotor activity, high-fat food intake, su-crose intake, or sucrose-induced CPP in separate groups ofcocaine naïve animals. Moreover, preliminary retrograde trac-ing suggests that the LHAad provides input into the ventraltegmental area (VTA). In summary, our findings indicate thatPNN expression in the LHAad: 1) is necessary for acquisitionof cocaine-induced CPP, 2) is predominantly co-localized withparvalbumin, and 3) is not necessary for normal locomotor oringestive behavior or sucrose-induced CPP. These data sug-gest that PNN-dependent neuroplasticity within the LHAad iscritical for the acquisition of cocaine-induced CPP. SUPPORT:Supported by NIH Grant DA033404 to Barbara A. Sorg, WSU-Alcohol and Drug Abuse Research Program Grant 124777 toJordan M. Blacktop

Calub, Catrina; Furtak, Sharon; Brown, Thomas (Cal-ifornia State University, Sacramento; Yale University) Auto-conditioning Hypothesis for Acquired Fear of Ultrasonic AlarmCries . Rats commonly emit 22 kHz ultrasonic vocalizations(USVs) in association with pain, fear, or anxiety/distress. Associal alarm or distress signals, these 22 kHz USVs are be-lieved to play a key role in group survival. Whereas the capac-ity to produce these USVs is innate, appropriate reactivity tothem requires experience. More specifically, 22 kHz USVs failto elicit freezing behavior (the classical fear index) in naïve lab-oratory rats. This fact raises the question: How do rats learnto react fearfully or defensively to these ethologically-importantsocial signals? A possible clue came from a study by Kim et al(2010). In their experiments, laboratory rats did react fearfully

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to alarm calls (evidenced by USV-elicited freezing behavior) ifthey received a series of foot shocks 24 hours earlier. Basedon several lines of evidence, these authors proposed that ac-quired fear of 22 kHz USVs depends on “autoconditioning” —an emotional learning process in which self-generated 22 kHzUSVs serve as auditory Pavlovian cues that become associ-ated with subsequent foot shocks. The present experimenttested this hypothesis by devocalizing one group of rats by sec-tioning the recurrent laryngeal nerve. Control animals under-went a nerve-sparing sham operation. Both groups receiveda series of foot shocks and were subsequently tested, in anovel context, for USV-elicited freezing. Recurrent nerve tran-section failed to prevent or even diminish USV-elicited freez-ing. Devocalized animals were statistically indistinguishablefrom the sham-operated controls, disconfirming an essentialprediction of the autoconditioning hypothesis. We consideralternative associative and non-associative mechanisms foracquired USV reactivity. SUPPORT: Social Sciences and In-terdisciplinary Studies (SSIS) Faculty Development Award atCalifornia State University, Sacramento

Campese, D. Vinn; Kim, T. Ian; LeDoux, E. Joseph (NewYork University) Different Forms of Conditioned MotivationDepend onDifferent Regions in the Amygdala. Aversive Pavlovian-to-instrumental transfer (PIT) is an effective way to isolate theconditioned motivation produced by an aversive conditionedstimulus (CS). This is seen as an elevation of avoidance re-sponding when an aversive CS is presented. However, dif-ferent forms of aversive conditioned motivation (i.e., specificversus general) have proven difficult to isolate and attributeto specific neural circuits. In appetitive PIT studies centralamygdala (CeA) has been linked to the general form of motiva-tion while basal amygdala (BA) has been linked to the specific

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form, which involves sensory-specific learning. Here we use awithin-subjects design where each subject received aversivePavlovian threat conditioning (PTC) with both tone-shock andnoise-klaxon arrangements. Following unsignaled Sidman ac-tive avoidance (USAA) training where subjects were trainedto shuttle to avoid shocks, each CS was tested separatelyfor their effect on USAA behavior. Following baseline tests,kappa opioid DREADDs (KORD) were infused into either theCeA or BA. After recovery each CS was tested following treat-ment with salvinorin-B (Sal-B) as well as the saline vehicle.Comparable to what has been found in appetitive studies, BAinhibition reduced specific PIT, but not general. CeA inhibitionreduced general PIT, but also reduced specific PIT. These re-sults suggest that different forms of aversive motivation maydepend on different microcircuits in the amygdala. SUPPORT:NIH Grant MH38774

Collins, Sean; Chau, Lily; Galvez, Roberto (University ofIllinois Urbana-Champaign) Associative learning temporar-ily increases SHANK neocortical expression consistent withanatomical plasticity. It has been well established that learninginduces synaptic modification in the neocortex. To examinethe molecular mechanism(s) mediating this process we haveutilized the associative learning paradigm whisker trace eye-blink conditioning (WTEB). During WTEB, subjects are pre-sented with a neutral whisker stimulation (CS) which is pairedwith a mild periorbital eye-shock (US). These stimuli are sep-arated by a stimulus-free trace interval. After multiple CS-USpairings, subjects learn that the CS predicts the US and elicitan eyeblink after the CS but before US onset. Utilization of thisparadigm has shown that primary somatosensory cortex is re-quired for both acquiring and retrieval of the learned associa-tion. In examining the neuronal mechanisms(s) mediating this

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learning event, our laboratory has demonstrated that spines inlayer IV of the barrel cortex exhibit a transient increase acrossdifferent phases of learning. The current study set out to deter-mine SHANK’s role in mediating this neocortical synaptic plas-ticity. The SHANK family is of particular interest due to theirlocalization in the post synaptic density (PSD) of excitatoryneurons. These proteins indirectly bind to NMDAR, AMPAR,and mGluR; thus playing a role in glutamate receptor organi-zation of the PSD. Knocking-out either SHANK1 or SHANK2results in behavioral impairments, and dysregulation of spinemorphology. These findings suggest that SHANK is involvedin learning-induced synaptic plasticity, and thus plays a rolein WTEB-induced neocortical spine modification. To exploreSHANK’s role in WTEB, adult C57BL/6 mice were randomlyassigned to one of six groups (acquisition, learned, over-trained,or stimulus matched unpaired controls). Our preliminary find-ings suggest that SHANK1 and SHANK2 in primary somatosen-sory cortex exhibit a learning-dependent expression profile thatcoincides with synaptic changes from our prior anatomical study.These analyses provide an initial understanding into themolec-ular mechanism(s)mediating neocortical learning-induced synap-tic plasticity.

Czerniawski, Jennifer; Guzowski, John F (University ofCalifornia - Irvine) Minocycline Treatment Blocks Cytokine-Induced Alterations in Hippocampal Circuit Activity and Con-text Discrimination Memory Impairment. Neuroinflammation isimplicated in cognitive deficits associated with aging, disease,and trauma. Recently, we demonstrated that systemic admin-istration of the bacterial endotoxin lipopolysaccharide (LPS)elevates mRNA expression of the proinflammatory cytokinesIL-1β, TNF-α, and IL-6 in the rat brain and produces specificmemory retrieval deficits in context discrimination and altered

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neural circuit activity in the hippocampus (Czerniawski & Gu-zowski, 2014; Czerniawski et al., 2015). These cytokines canhave a peripheral source, but can also be produced and re-leased centrally by microglia and astrocytes. In order to testthat LPS dysregulates neural circuit activity and impairs cog-nition via cytokines released from microglia, we blocked mi-croglial activation with systemic administration of minocycline,a semi-synthetic tetracycline antibiotic that crosses the BBB.Rats were trained in context discrimination conditioning, in whichthey were placed into 2 similar behavioral chambers daily, withone of the environments paired with a brief, mild footshock.Upon reaching discrimination criterion, each subject receivedan intraperitoneal (i.p.) injection of minocycline (50 mg/kg) orsaline and a second dose the next day. Thirty minutes afterthe second dose of minocycline or saline, LPS (150 µg/kg, i.p.)or saline was administered, 6 h prior to testing in each of thecontexts. Minocycline treatment blocked the LPS-induced: 1)elevation of IL-1β and TNF-α in dorsal hippocampus, 2) thedysregulation of hippocampal circuit activity and 3) the impair-ment in context discrimination memory retrieval. In a separateexperiment, minocycline (2 µg/side) infused directly into dor-sal hippocampus robustly blocked the LPS-induced deficits incontext discrimination memory retrieval. Together these find-ings provide a direct causal link between cytokine expressionin the hippocampus and cognitive deficits during neuroinflam-mation. Lastly, this study provides a strong mechanistic basisfor the potential use of minocycline or related compounds inthe treatment of human patients with impaired cognitive func-tion resulting from neuroinflammation. SUPPORT: AG00096-31, NIH NRSA Neurobiology of Aging; NIH R01 MH082930

Daniels, W. Carter ; Sanabria, Federico (Arizona StateUniversity) The Effect of Chronic Nicotine Administration on

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Sign- and Goal-Tracking: A Pilot Study. Nicotine appears tobe a relatively weak primary reinforcer that, nonetheless, en-hances the value of non-nicotine rewards. Consistent with thishypothesis, nicotine appears to enhance incentive motivation,facilitating the approach and handling of stimuli associatedwith rewards. It is possible that chronic exposure to nicotineincreases the sensitivity to the enhancing effects of nicotineon incentive motivation, thus amplifying the dependence of in-dividuals to nicotine. To test this hypothesis, 16 adult maleWistar rats received sub-cutaneous (s.c.) administrations ofnicotine (NIC: 0.6 mg/kg) or saline (SAL) twice a day, once inthe morning and once in the evening, for 12 consecutive days.Two days after the last administration, all rats were trainedon a discriminated Pavlovian conditioned approach task, withlevers serving as CS+ and CS-, for 12 consecutive sessions.In a two-session nicotine probe (7th and 8th session of train-ing) all rats received one s.c. administration of 0.6 mg/kg ofnicotine. Sign- and goal-tracking (lever pressing and head-entries, respectively) in the presence of the CS + and CS- didnot differ significantly between groups NIC and SAL until thenicotine probe. Following the probe, rats in group NIC weremore likely to sign-track than prior to the probe, and relative torats in group SAL during presentation of the CS+ and not theCS- or inter-trial interval (ITI). The probe also increased goal-tracking in the presence of CS- for rats in group SAL and dur-ing the ITI for group NIC. These results suggest that chronicexposure to nicotine increases the sensitivity to nicotinic en-hancement of incentive motivation.

de Solis, Christopher; Holehonnur, Roopa; Banerjee,Anwesha; Luong, Jonathan, Lella Srihari; Ho, Anthony;Pahlavan, Bahram; Ploski, Jonathan (University of Texas atDallas) Viral Delivery of shRNA to Amygdala Neurons Leads

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to Neurotoxicity and Deficits in Pavlovian Fear Conditioning.The use of viral vector technology to deliver short hairpin RNAs(shRNAs) to cells of the nervous system of many model organ-isms has been widely utilized by neuroscientists to study theinfluence of genes on behavior. However, there have been nu-merous reports that delivering shRNAs to the nervous systemcan lead to neurotoxicity. Here we report the results of a seriesof experiments where adeno-associated viruses (AAV), thatwere engineered to express shRNAs designed to target knownplasticity associated genes (i.e. Arc, Egr1 and GluN2A) orcontrol shRNAs that were designed not to target any rat geneproduct for depletion, were delivered to the rat basal and lat-eral nuclei of the amygdala (BLA), and auditory Pavlovian fearconditioning was examined. In our first set of experiments wefound that animals that received AAV (3.16E13-1E13GC/mL),designed to knockdown Arc (shArc), or control shRNAs tar-geting either luciferase (shLuc), or nothing (shCntrl), exhibitedimpaired fear conditioning compared to animals that receivedviruses that did not express shRNAs. Notably, animals thatreceived shArc did not exhibit differences in fear conditioningcompared to animals that received control shRNAs despitegene knockdown of Arc. The highest dose of shRNA virusexamined (3.16E13GC/mL), showed a significant increase inmicroglia activation as indicated by an increase in IBA1 im-munoreactivity. In our final set of experiments, we infusedviruses at a titer of 1.60E+12GC/mL (designed to (Arc, Luc,nothing or shRNAs designed to target Egr1 (shEgr1), or GluN2A(shGluN2A) and found that all groups exhibited impaired fearconditioning. However, the shGluN2A group exhibited signifi-cantly impaired fear conditioning compared tomost of the groups,indicating that gene specific deficits in fear conditioning couldbe observed utilizing shRNAs. Collectively, these data indi-

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cate that viral mediated shRNA expression was toxic to neu-rons in vivo, under all viral titers examined and this toxicity insome cases may be masking gene specific changes in learn-ing. Therefore, the use of this technology in behavioral neuro-science warrants a heightened level of careful consideration.SUPPORT: RMH096202A, RMH100650A and The Universityof Texas at Dallas

Elkin, Magdalyn E.; Freeman, JohnH. (University of Iowa)Ontogenetic Changes In Anterior Cingulate Cortical Activityduring Trace Eyeblink Conditioning. . The ontogeny of traceeyeblink conditioning is believed to be dependent upon mat-uration of forebrain structures such as the anterior cingulatecortex (ACC) and hippocampus. (Goldsberry et al., 2015, J.Neurosci., 35:4238). Although neuronal responsiveness in theACC during trace eyeblink conditioning has been studied inadults, there is a paucity of research concerning its role in thedeveloping animals. The goal of the current study was to ex-amine the development of neuronal activity in the ACC whiledeveloping rats were trained in trace eyeblink conditioning. Weimplanted moveable tetrodes in rat pups on postnatal days (P)17, 19, 22 and 29. The rat pups were given one of day restand then trained on trace eyeblink conditioning twice a dayfor three days, for a total of six sessions. Trace eyeblink con-ditioning involved presentation of a 250 ms tone conditionedstimulus CS, followed by a 500 ms stimulus-free trace intervalwhich terminated in a 25 ms periorbital shock unconditionedstimulus (US). The rate of acquisition of trace conditioning in-creased across age groups. The spontaneous firing rate ofACC neurons also increased as a function of age. During con-ditioning trials there was a substantial developmental increasein the percentage of ACC neurons responsive to individual trialevents (i.e., the CS, trace interval, US) and combinations of

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trial events from the first paired training session. The resultsindicate that the ACC undergoes developmental changes inneuronal coding of trial events. SUPPORT: NIH #NS038890

Farley, Sean; Freeman, John (The University of Iowa)Cerebellar Feedback is Necessary for Learning Related Ac-tivity in the Medial Auditory Thalamic Nuclei During EyeblinkConditioning. We previously hypothesized that the cerebellumfacilitates activity in its sensory inputs during learning. In thecurrent study, we examined changes in neuronal firing patternsin the medial auditory thalamic nuclei (MATN) during cerebel-lar inactivation with muscimol. Rats were trained in delay eye-blink conditioning with alternating sessions of cerebellar inac-tivation or vehicle infusions with simultaneous tetrode record-ings in the MATN. Eyeblink conditioning sessions consisted ofa 2 kHz tone conditioned stimulus (CS) paired with a perior-bital stimulation unconditioned stimulus (US). Rats were im-planted with an infusion cannula directed at the anterior inter-positus nucleus (AIN) ipsilateral to the conditioned eye. MATNcells were classified as short latency, long latency, sustained,or no response based upon their firing rates during the CS.After rats reached a conditioned response (CR) criterion, ses-sions were separated into two 50-trial blocks that were char-acterized as pre-infusion (1-50) or post-infusion (51-100). Af-ter the pre-infusion block saline or muscimol was infused intothe AIN. Within-subject data from across rats were combinedin a pre- and post-infusion neuronal analysis of the CS pe-riod. MATN long latency neuronal activity during the CS pe-riod was significantly depressed after muscimol infusions com-pared to controls. The majority of MATN neurons with longlatency responses to the CS altered their firing patterns to noresponse with AIN inactivation. Additionally, a significant pro-portion of sustained response cells changed to short latency

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responses with AIN inactivation. These firing pattern changesof individual cells with AIN inactivation support the hypothesisthat cerebellar learning is driving learning-related activity in theMATN during eyeblink conditioning. SUPPORT: MH080005;NS088567

Furtak, Sharon; Calub, Catrina; Potter, Nicole (Califor-nia State University, Sacramento) Perirhinal Cortex Involve-ment in Fear Extinction to a Discontinuous Visual Stimulus.The perirhinal cortex (PER) is known to be involved in highlevel perceptual processing. One hypothesis is that PER func-tions to unitize stimuli across time or across sensory modali-ties (Kent & Brown, 2012; Graham et al., 2006). While manyfindings have supported the role of PER in fear acquisition todiscontinuous auditory stimuli and polymodal stimuli (Bucci,Phillips, & Burwell, 2000; Bucci, Saddoris, & Burwell, 2002;Corodimas & LeDoux, 1995; Kholodar-Smith, Allen, & Brown,2008; Kholodar-Smith, Boguszewski, & Brown, 2008), to dateno study has evaluated PER involvement in processing suchstimuli during fear extinction. In the present study, Sprague-Dawley male rats were infused with muscimol, a GABA ago-nist, to temporarily inactivate the PER during extinction train-ing. All subjects were surgically implanted with cannulae tar-geting PER bilaterally. Following recovery, animals were trainedon a three-day fear extinction paradigm. On Day 1, animalsunderwent fear conditioning, in which they were presentedwith5 trials of a discontinuous visual light stimulus (conditionedstimulus; CS) paired with a foot shock (unconditioned stim-ulus; US). On Day 2, animals received PER infusions of eithermuscimol or saline prior to extinction training, in which theyreceived 20 trials of the CS alone. On Day 3, extinction recallwas assessed by presenting an additional 15 CS trials. Freez-ing behavior was recorded throughout the experiment. Results

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showed that bilateral muscimol infusions into the PER duringextinction training impaired extinction recall to a discontinuouslight CS, as indicated by significantly higher levels of freezingin muscimol infused animals than saline control animals dur-ing extinction recall. The results suggest that particular cuesmay engage brain regions outside what is typically consideredthe fear extinction neural circuit. Here, for the first time resultssupport a role for PER involvement in fear extinction, perhapsdue to the discontinuous nature of the CS. SUPPORT: Califor-nia State University, Sacramento SSIS/UEI Funding

Gahtan, Ethan; Bishop, Benjamin (Humboldrt State Uni-versity) Light-Evoked Diving Reflex In Zebrafish Larvae. Es-cape behaviors have been studied in many organisms by neu-roscientists seeking detailed, cellular- and synaptic-level de-scriptions of functional circuits. Escapes are useful becausethey can be elicited repeatedly and have consistent kinemat-ics. Analysis of escape circuits in fish have revealed neuralmechanisms for lateral movements, such as commissural pro-jections and population coding of escape turn angle. However,while most fish navigate in 3 spatial dimensions, few studieshave examined neural mechanisms of vertical movements dur-ing escapes. We characterized vertical escape swimming inzebrafish larvae using synchronized imaging from two cam-eras viewing a 10cm3 tank. Escapes elicited by dimming ofambient light consistently elicited downward spiral swimming(dives). At 20s post dimming, larvae showed more vertical (-18.8±2mm) than horizontal (3.2±0.6mm) displacement. Theaverage slope of dives was -1.9±.35, meaning larvae moveabout twice as fast vertically than horizontally along their spi-ral paths. In a tubular tank with more vertical (400mm) thanhorizontal (100mm) range, vertical movement 120s after lightdimming was -353±8.39mm ( 70 body lengths downward).

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Dives usually began within 1s after light dimming and contin-ued until the tank bottom was reached. Maximum descent ratewas 10.75mm/s (at 58s post dimming), and average descentrate was 5.41±0.24mm/s. Auditory taps also elicited rapidescape swimming with equivalent total distance traveled 20spost stimulus but with significantly less vertical and more hori-zontal displacement than on dimming-evoked escapes. Theseresults suggest that light dimming-evoked spiral diving in lar-val zebrafish may be a protean escape reflex to specific typesof predation threats, and that neural circuit models of escapecontrol must look beyond mechanisms for lateral movementsand also consider vertical movement control elements. Thisresult parallels other cases in behavioral neuroscience wherelimitations of the behavioral testing environment limit possibleconclusions about underlying neural mechanisms.

Garr, Eric; Delamater, Andrew R. (Graduate Center ofthe City University of New York; Brooklyn College) ActionSequences are Sensitive to Reward Devaluation. Habitual re-sponses can clearly be dissociated from goal-directed actionsboth at the behavioral and neural levels. Explanations of howgoal-directed actions transition to habitual responses have tra-ditionally focused on the different associations that underliebehavior, with response-outcome associations thought to con-trol behavior early in training while stimulus-response associa-tions dominate later in training. Recent computational model-ing from the field of reinforcement learning suggests that habitsare the result of automatic, stereotyped action sequences (Dez-fouli & Balleine, 2012). To determine if stereotyped action se-quences are goal directed, different groups of rats were giventhe opportunity to earn food rewards under different heteroge-neous instrumental chain schedules involving two levers. Onegroup (LLRR) learned to press the left lever twice followed by

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two right lever presses to earn a grain pellet. Another group(LRRR) was initially unconstrained in which four lever-presssequences earned pellets, but was later shifted to an LRRRschedule. Finally, another group (LR) learned to press the leftlever followed by the right lever for pellets. In all cases, ac-curacy increased over sessions while variability decreased. Aselective satiation manipulation was given at the end of eachtraining procedure in order to assess goal-directedness. Eachrat was sated on either the earned grain pellets or equally po-tent sucrose pellets, after which they were given a five-minuteextinction test in which no pellets were earned for pressing thelevers. Each rat was sated on both types of pellets over differ-ent days. The extinction tests revealed that each group wassensitive to devaluation—rats generally executed less targetsequences while sated on the earned outcome compared towhen sated on the other outcome. Future studies will addressthe role of extended training on action sequence sensitivity toreward devaluation and selective PIT tests. SUPPORT: TheGraduate Center of the City University of New York; NIDA SC1DA034995

Gonzalez, Sarah T.; Fanselow, Michael S. (University ofCalifornia, Los Angeles) The Neural Mechanisms of SafetyLearning in Mice. Safety learning is the ability to suppressfear in the presence of a stimulus that signals the absence ofan aversive event, yet little is known about its neural mech-anisms. Here we investigated whether safety learning wasassociated with altered activity in the medial prefrontal cor-tex in mice. Mice were divided into three conditions: the FearLearning condition, in which presentations of a light were im-mediately followed by a foot shock, the Safety Learning con-dition in which the light signaled the absence of the shock forat least 2 minutes, and the Random Control condition in which

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the light provided no information about the occurrence of theshock. Following eight days of training, all subjects received asummation test in which the light was presented in a secondcontext that had been paired with shock.

Activity of the prelimbic and infralimbic regions of the me-dial prefrontal cortex after the summation test was comparedusing expression of the immediate early gene arc, a markerof cellular activity. Recent investigations have suggested thatthe infralimbic region may be involved in fear extinction, a dis-tinct learning process in which a stimulus that previously sig-naled an aversive event is repeatedly presented alone until itno longer produces a fear response. While safety learning andextinction are distinct learning processes, both are believedto involve the development of a new association in which thestimulus signals the absence of the aversive event, and maytherefore involve similar neural mechanisms. Arc protein lev-els suggested that safety learning may involve increased activ-ity in the infralimbic cortex. SUPPORT: NIH #3RO1MH062122

Goode, Travis; Jin, Jingji; Holehonnur, Roopashri; Ploski,Jonathan; Maren, Stephen (Texas A&M University) Combi-natorial DREADD Silencing of Ventral Hippocampal NeuronsProjecting to Infralimbic Cortex Prevents Fear Renewal. Extin-guished fear to a conditioned stimulus (CS) renews outside ofthe place or context in which extinction training occurred. Herewe used designer receptors exclusively activated by designerdrugs (DREADDs) to test the hypothesis that projections fromthe ventral hippocampus (VH) to the infralimbic region (IL) ofthe medial prefrontal cortex mediate fear renewal. Rats re-ceived bilateral VH infusions of inhibitory DREADD virus (AAV-CaMKiiα-hM4D-mCherry), Cre-dependent DREADD silencer(AAV-hSyn-DIO-hM4D-mCherry), or control virus (AAV-CaMKiiα-GFP). In rats receiving Cre-dependent DREADD virus, the IL

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was infused with a canine adenovirus (CAV) to retrogradelyexpress Cre and inhibitory DREADDs in VH:IL circuits. 2-4wks later, rats were conditioned and extinguished (in separatecontexts) to an auditory CS (10 s, 2 kHz, 80 dB tone; uncondi-tioned stimulus [US] = 2 s, 1 mA footshock). Freezing behav-ior served as the index of fear. 24 hrs after extinction, and ina counterbalanced within-subjects design, rats were tested tothe CS outside of the extinction context on and off CNO (1 or3 mg/kg, i.p.). As predicted, DREADD-mediated inactivationof either VH or VH neurons projecting to IL disrupted fear re-newal as compared to vehicle treatment or reporter-only con-trols. These data are consistent with the possibility that, duringfear renewal, the VH inhibits the IL to limit the suppression offear to an extinguished CS. SUPPORT: NIH R01MH065961-12A1 to S.M.

Goosens, Ki; BarbaraGisabella, Junmei Yao (MassachusettsInstitute of Technology) Enhanced Growth Hormone in Amyg-dala Neurons Dysregulates Associative Fear Memory Alloca-tion. Chronic stress produces a long-lasting vulnerability toexcessive fear memory formation following trauma, but themechanisms by which stress leads to strong fear memoriesare not understood. One possibility is that individual neuronsshow greater fear-related plasticity in a stressed brain com-pared to an unstressed brain. A second possibility is that strongerfear memories, like those observed in stress-exposed individ-uals, recruit a larger number of neurons during fear memoryencoding. We previously found that chronic stress robustlyupregulates growth hormone (GH) protein expression in amyg-dala tissue and hypothesized that GHmay be an unrecognizedgrowth factor within the amygdala, where it may contribute tostress-associated disorders that involve an over-encoding oftraumatic memories, such as post-traumatic stress disorder

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(PTSD). Here, we examined the effects of excess GH on neu-ronal morphology within the amygdala and also on neuronalrecruitment during fear memory formation. We found that over-expression of GH within the amygdala nearly doubles spinedensity on both primary and secondary branches of pyrami-dal amygdala neurons; this increase was observed for thin,mushroom, and stubby spines. We also found that GH overex-pression nearly doubles the number of neurons that expressthe immediate early gene cFos after auditory fear condition-ing, suggesting that stress promotes fear memory formationby increasing the size of the neuronal networks in the amyg-dala that encode memory. Additionally, GH-overexpressingneurons had a significantly greater probability of expressingcFos as compared to neighboring neurons that did not overex-press GH. Because activity-dependent release of GH can pro-mote synaptic plasticity, this provides a mechanism by whichindividual neurons may be predisposed to stronger synapticplasticity during fear memory formation. Thus, chronic stressmay enhance fear memory formation by promoting larger andstronger fear memories through upregulation of GH. This workprovides a novel link between GH and psychiatric disease.SUPPORT: NIMH (R01 MH084966), and the U.S. Army Re-search Office and the Defense Advanced Research ProjectsAgency (grant W911NF-10-1-0059) to KAG

Gould, Thomas (Temple University) Adolescent NicotineExposure Alters Adult Contextual Fear Conditioning. Adoles-cent nicotine use is a serious health issue. The Center for Dis-ease Control and Prevention reports that every day 3,800 ado-lescents smoke their first cigarette, that e-cigarette use in thisage group has tripled in the last year and is now higher thanconventional cigarette use, and that nearly 90% of adult smok-ers initiated smoking by age 18. While it is clear that tobacco

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product use and nicotine addiction contributes to substantialhealth problems in the United States, increasing evidence sug-gests that adolescent nicotine exposuremay also cause healthproblems beyond those commonly associated with tobaccoproducts. Specifically, adolescent nicotine use may producelong-term cognitive deficits. Early adolescent tobacco use wasassociated with memory deficits and late adolescent smokershad cognitive deficits that emerged after initiation of smoking.These effects were also seen for secondhand tobacco smokeexposure. Children 8-15 years old exposed to secondhandsmoke had higher rates of attention-deficit/hyperactivity dis-order. Long-lasting deficits in cognition associated with ado-lescent tobacco use are especially troubling because multiplemental illnesses that have symptoms that include changes incognition are also associated with higher rates of tobacco use.Thus, adolescent tobacco use may not only lead to addictionbut it may contribute to adult cognitive deficits and exasper-ate cognitive symptoms associated with mental illness. An ini-tial study in mice found that adolescent nicotine exposure issufficient to produce adult deficits in hippocampus-dependentlearning measured with contextual fear conditioning. Prelimi-nary data suggest that these deficits may be associated withaltered brain acetylcholinergic function. Thus, this presen-tation will examine behavioral effects of adolescent nicotineexposure on adult learning, factors that modulate these ef-fects, and cholinergic manipulations that ameliorate associ-ated deficits in contextual fear conditioning. SUPPORT: NIHDA017949

Gray, Michael S.; Lynch III, Joseph F;Winiecki, PatrickiA.; Jasnow, Aaron M. (Kent State University) Presynap-tic GABAB(1a) Receptors Preserve Context Memory DuringConsolidation. Anxiety disorders, such as PSTD, are charac-

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terized by generalization of fear responses to neutral stimuli.GABA-mediated presynaptic inhibition plays a critical role infear memory specificity, as animals with genetically deletedpresynaptic GABAB(1a) receptors cannot discriminate betweenCS+ andCS- tones. We have previously identified that GABAB(1a)receptors play an important role in maintaining memory preci-sion for context. GABAB(1a)-/- mice show generalized fear toa neutral context 24 hours after training, but not 2 or 6 hoursafter training (Cullen, et al. 2014). The same pattern is ob-served with object location and recognition, suggesting thatthis receptor subtype affected the consolidation and retrievalof contextual and spatial memories. To examine more pre-cisely if GABAB(1a) receptors are involved in consolidation orretrieval of a precise fear memory, we administered infusionsof the selective GABAB(1a) receptor antagonist, CGP 36216,intracerebroventricular (ICV), or specifically into the dorsal hip-pocampus or anterior cingulate cortex (ACC), at different timepoints during and after context fear conditioning. Post-trainingICV or dorsal hippocampal infusions resulted in fear general-ization to the neutral context 24 hours later. However, ICV, dor-sal hippocampus, or ACC infusions prior to testing did not re-sult in context generalization. These data suggest that presy-naptic inhibition through GABAB(1a) receptor activation playsan important role in the consolidation, but not retrieval, of pre-cise contextual memories, as we originally had concluded. Thus,with a combination of genetic and pharmacological manipu-lations we have more precisely identified the critical role ofGABA-mediated presynaptic inhibition in the formation of pre-cise contextual memories. SUPPORT: Whitehall Grant, FarrisFamily Foundation

Hafenbreidel, Madalyn; Rafa Todd, Carolynn; Smies,Chad. W.; Twining, Robert C.; Mueller, Devin (University

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of Wisconsin, Milwaukee) Blocking Infralimbic Basic Fibrob-last Growth Factor (bFGF or FGF2) Facilitates Extinction ofDrug Seeking. Stimulant drug use results in structural andfunctional changes in reward-related brain regions, which mayunderlie the persistence of compulsive drug seeking and re-lapse that characterizes drug addiction. Neurotrophic factors,such as basic fibroblast growth factor (bFGF or FGF2), arenecessary for neuronal survival, growth, and differentiation,and may mediate drug-induced morphological changes. Fol-lowing cocaine exposure, bFGF is increased in brains regionssuch as the infralimbic medial prefrontal cortex (IL-mPFC). TheIL-mPFC is necessary for extinction, but if drug-induced over-expression of bFGF in this region affects extinction is unknown.Thus, we aimed to determine if blocking bFGF in IL-mPFCwould facilitate extinction following cocaine self-administration(SA). Rats were trained to lever press for i.v. infusions of co-caine prior to extinction. Extinction consisted of four 30 minextinction sessions, in which rats received IL-mPFC infusionsof a neutralizing antibody against bFGF prior to each session.Extinction retention was tested during a subsequent 90 minextinction session. Blocking bFGF in the IL-mPFC decreasedlever pressing during the 90 min extinction session, indicatingfacilitated extinction. In contrast, blocking bFGF and returningrats to their home cage had no effect on subsequent extinc-tion. Next, we examined if bFGF protein expression was al-tered following extinction. Rats were trained to self-administercocaine as before with half undergoing extinction or not. Addi-tionally, rats that were reinforced with sucrose and underwentextinction or not, rats that received yoked-saline infusions thatwere paired with cocaine SA administering rats (extinction ornot), and a naïve control were included. bFGF protein expres-sion in the IL-mPFC was only increased following cocaine SA,

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an effect reversed by extinction. These results suggest thatcocaine-induced over-expression of bFGF in the IL-mPFC in-hibits extinction, as reducing bFGF expression during extinc-tion permits rapid extinction. Therefore, targeted reductions inbFGF during therapeutic interventions could enhance addic-tion treatment outcomes. SUPPORT: R01 DA038042; Univer-sity of Wisconsin-Milwaukee Graduate School

Hanson, Erica E., Mitchell, Suzanne H. (Oregon Health &Science University) Fos expression after exposure to an effortdiscounting procedure. Objective: Apathy is a hallmark of nu-merous psychiatric disorders. However our understanding ofthe processes regulating the unwillingness to engage in effort-ful responses is unclear. This research used themeasurementof a marker of neuronal activity to determine the contribution ofdifferent brain areas to the decision to work for a food reward.

Methods: 64 Long-Evans rats (N=32 per sex) were usedin this study. Rats were divided into three groups: a food-restricted experimental group, a food-restricted group controlgroup, and a baseline control group that wasn’t food restricted.Rats in the food-restricted experimental group were trainedon an effort-discounting task based upon a modified adjustingamount procedure (Richards, Mitchell et al 1997, J Exp AnalBehav 67: 353) in which the subjective value of 150-µL of su-crose wasmeasured. Discounting in the trained group was es-tablished by testing rats on five effort levels (0.01, 0.15, 0.35,0.6, 0.9 Ns). Un-trained control rats were placed in the oper-ant chambers, but did not complete the task. Rats were eutha-nized on their last session so that brain tissue could be stainedfor cFos, a habituating marker of neural activation. Numbersof Fos-positive cells were counted visually, and compared be-tween groups for each region.

Results: For the trained rats, the subjective value of the

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150-µL reward decreased as a function of increasing effort.When rats were tested at a single cost magnitude (0.6 Ns)prior to their last session, the subjective value of the 150-µLsucrose was stable across sessions. Preliminary cell-countingsuggests an enrichment of cFos-positive cells in accumbensand cingulate, for food-restricted, experimental animals overcontrols.

Conclusions: These results are consistent with the viewthat the striatum is involved with the choice to perform effortfor a food reward, rather than the value of the reinforce itself.SUPPORT: NIH # T32 DA007262

Heroux, Nicholas; Robinson-Drummer, PatreseA.; Rosen,Jeffrey B.; Stanton, Mark E. (University of Delaware) Roleof NMDA Receptors in the Acquisition and Retention of theCPFE in Adolescent Rats. The context preexposure facilita-tion effect (CPFE) is a contextual fear conditioning paradigm inwhich learning about the context, acquiring the context-shockassociation, and retrieving/expressing contextual fear are tem-porally dissociated. The current set of experiments examinedthe involvement of NMDA receptors across all phases of con-textual fear learning in the CPFE in developing animals. Exper-iment 1 found that systemic injections of .1mg/kg of the non-competitive NMDA receptor antagonist MK-801 given beforemultiple context preexposure disrupted subsequent 24hr re-tention test freezing after training. Experiment 2 demonstratedthat pre-training MK-801 disrupts not only the acquisition andimmediate expression of contextual fear measured by a post-shock freezing test, but also subsequently disrupts freezing ina retention test 24 hours later. Experiment 3 employed pre-retention systemic injections of MK-801 and showed that ex-pression of contextual fear via a 24hr retention freezing testdoes not depend on NMDA receptors and that freezing deficits

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resulting fromMK-801 reflect learning rather than performanceeffects. Experiment 4 found that the consolidation of contex-tual information was partially disrupted by post-preexposureMK-801 whereas the consolidation of contextual fear was notdisrupted by post-training MK-801 administration. Finally, Ex-periment 5 reexamined the effects of pre-training MK-801 onsubsequent immediate postshock and 24hr retention tests byemploying a dose-response design and found that higher dosesof MK-801 (.1mg/kg) disrupt both postshock and retention testfreezing while lower doses of MK-801 (.025 or .05mg/kg) onlydisrupt retention freezing. In summary, the acquisition of con-textual information during context preexposure and of the context-shock association during the training day of the CPFE is NMDAreceptor dependent in adolescent rats. Future experimentswill employ DHPC, BLA, and mPFC cannula in an attempt tolocalize these effects, and will examine the ontogeny of post-shock freezing within the CPFE and sCFC. SUPPORT: NIHgrant R01 HD075066-01A1 to MES and JBR

Hersman, Sarah; Hoffman, Annie; Hodgins, Lili; Shieh,Shannon; Lam, Jamie; Fanselow, Michael S (UCLA) Dis-sociation of Cholinergic Modulation in Dorsal Hippocampusand Basolateral Amygdala on Stress-enhanced Fear Learning.An inappropriately high fear response can manifest as an anx-iety disorder such as post-traumatic stress disorder (PTSD).While the contextual aspect of the fear memory is dependenton the dorsal hippocampus (DH), the associative emotionalmemory is dependent on the basolateral amygdala (BLA). Inboth regions, acetylcholine (Ach) provides an important signalfor this learning. Open questions are how these neural sub-strates change during maladaptive fear learning, and whetherinhibiting Ach disruptsmaladaptive fear. Using Stress-EnhancedFear Learning (SEFL), which models some aspects of PTSD

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in rats, we tested whether Ach in DH and BLA is required formaladaptive fear. To dissociate the effect of Ach in DH andBLA, we infused scopolamine or vehicle into these brain re-gions immediately before SEFL, and tested fear in both thetrauma context and a novel context after a mild stressor inthat novel context. The results show that during learning, Achacting within both DH and BLA is required for sensitization offuture fear learning. Rather than simply sensitizing the BLA,SEFL requires functional signaling in both the DH and BLA;this larger circuit, and the requirement for Ach, suggests fu-ture research and therapeutic targets for human PTSD. SUP-PORT: Ruth L. Kirschstein National Research Service Award(T32 - NS058280), NIMH Grant RO1 62122, the Narsad Dis-tinguished Investigator Award # 18667, and the ARCS Foun-dation Fellowship.

Huckleberry, Kylie A.; Ferguson, LauraB.; Drew, MichaelR. (University of Texas at Austin) Behavioral Mechanisms ofContext Fear Generalization. There is growing interest in gen-eralization of learned contextual fear, driven in part by the hy-pothesis that mood and anxiety disorders stem from impairedhippocampal mechanisms of fear generalization and discrim-ination. However, there has been relatively little investigationof the behavioral and procedural mechanisms that might con-trol generalization of contextual fear. We characterized contextfear generalization in two common conditioning protocols—foreground and background contextual fear conditioning—andassessed the relative contribution of different context featuresto generalization. In Experiment 1, C57bl6/j mice were fearconditioned in A, and then tested for fear both of A and of analternate context created by varying a subset of A’s elements.Generalization was greater when the two contexts differed onlyin shape than when contexts differed only in odor or floor con-

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figuration. The results suggest that floor configuration andodor are more salient features than chamber shape. In Ex-periment 2, we compared context fear generalization in back-ground versus foreground context conditioning. Generaliza-tion to a similar context (A′) was stronger after foreground con-ditioning than background conditioning. However, foregroundconditioning also generated higher levels of contextual fear;when the levels of fear generated by the two procedures wereequated by varying the number of conditioning trials, back-ground and foreground procedures produced approximatelyequivalent levels of generalization. In Experiment 3, we as-sessed the effects of test order. Generalization between A andA′ was weaker when mice were tested in A first. Data suggestthat the test order effect is driven by extinction occurring duringthe first test. In conclusion, results demonstrate that contextgeneralization is highly sensitive to procedural variations andlikely reflects the operation of multiple interacting psychologi-cal and neural mechanisms. SUPPORT: R01 M102595; R00MH083943

Huda, K. Rebecca; Latsko, Maeson S; Gilman, Lee T;Jasnow, Aaron M. (Kent State University) Resistance to So-cial Defeat Stress is Characterized by Poor Behavioral Inhibi-tion; Assessment in Passive Avoidance. Individual differencesin vulnerability to social stress have been reported in recentchronic stress models. Following social defeat, mice are char-acterized as being either resistant (high social approach be-havior) or susceptible (low social approach behavior) to so-cial defeat stress as observed in a subsequent social interac-tion test with a novel conspecific. Traditionally, the resistantphenotype has been thought to be a well-suited model for hu-man resilience to social stress. However, our lab has iden-tified a number of behaviors suggesting that resistant mice

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have deficits in behavioral inhibition. For example, resistantmice have increased fear to a neutral cue (CS-) compared tosusceptible mice. These findings fit our earlier report that re-sistant mice also have impaired extinction learning comparedwith susceptible mice. Taken together, these data suggest thatresistant mice may be characterized by poor behavioral or re-sponse inhibition and social approach behavior. To further testthis hypothesis, we are currently examining the relationshipbetween susceptibility and resistance to social defeat and per-formance on a passive-avoidance task, which requires miceto inhibit their natural tendency to cross into the dark chamberafter having experienced footshock. We hypothesize that re-sistant mice will demonstrate significantly shorter step-throughlatencies during a retrieval test compared to susceptible andcontrol mice, which might indicate impaired response inhibit inthis phenotype. These findings will help continue to charac-terize behavioral and neurobiological features associated withthe resistant phenotype.

Hui, May; Zelikowsky, Moriel; Anderson, David (Califor-nia Institute of Technology) Tac2 mediates chronic stress inmice. Stress is a behavioral response found in virtually all an-imal species. Recently, Tachykinin 2 (Tac2), which encodesthe neuropeptide Neurokinin B (NKB), has been implicatedin fear memory consolidation. We were interested in explor-ing the possibility of a larger role for Tac2 in mediating stress.In particular, we examined whether systemic and local antag-onism of the NKB-specific receptor, NK3, with the drug os-anetant, could alter the effects of various manipulations to in-duce stress. Mice were subjected to chronic stress comprisedof either social isolation, restraint stress, or footshock, givendaily across 14 days. Mice were then tested for stress-inducedchanges in behavior using a looming assay (as a measure of

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innate defensive behavior) and trace fear conditioning (as ameasure of cognitive function and stimulus reactivity). At test,mice were treated with a systemic injection (i.p.) of osanetantor microinfusions into the dorsal-lateral striatum or the dorsalbed nucleus of the stria terminalis. We found that osanetantwas able to buffer against the effects of chronic stress. More-over, we found that systemic administration of the NK3 agonistsenktide was able to induce stress-like effects in non-stressed,group-housed control mice. Collectively, our data point to abroad role for Tac2 in the regulation of chronic stress. SUP-PORT: Caltech Samuel N. Vodopia and Carol J. Hasson SURFFellowship

Johnson, Brandon. A.; Wilson, W. Jeffrey (Albion Col-lege) Light-induced Attenuation of Response to Light in theEarthworm Lumbricus terrestris. Earthworms (Lumbricus ter-restris) locomote in response to light. In examining their re-sponses to repeated 10-min lights over an extended periodof time (24 or 48 hr) we noted anecdotally that the responseto light seemed smaller when the light came soon after an-other light. We set out to examine this light-induced attenua-tion more systematically. Earthworm locomotion was recordedas movement of a computerized running wheel; data were notused for a small number of worms that did not move at all orthat were dead at the end of the session. In Experiment 1independent groups (n=16) of worms received multiple pre-sentations of light of duration 1, 2, 5, or 10 min, separated byperiods of darkness equal to 1, 2, 3, 6, and 9 times the light du-ration. Responses were equivalent following all of these inter-vals of darkness, but were attenuated compared to responseto the first light. Cumulative effect of repeated exposure to lightmight have obscured meaningful differences; examination ofthe reduced response to the second light compared to the first

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for each worm suggested that this might be the case. Exper-iment 2 exposed each worm to light (1-, 2-, 4-, 8-min dura-tion, n=8/group) twice, with an intervening period of dark (2, 8,32, 128 min). Control worms received light only at the secondtime. Response to the second light was significantly attenu-ated for long-duration lights (4 & 8 min), but not short-duration.Duration of the dark interval did not matter. Thus earthwormsrespond less to a second exposure to a light of sufficiently longduration for up to 128 min after initial exposure. We think thisattenuated response reflects a habituation-like phenomenonrather than a sensory or motor effect. SUPPORT: Albion Col-lege Dept. of Psychological Science, and Foundation for Un-dergraduate Research, Scholarship, & Creative Activity

Kennedy, Bruce C; Kohli, Maulika; Maertens, Jamie;Marell, Paulina; Gewirtz, JonathanC (University of Minnesota)Conditioned Object Preference: A Novel Measure of Drug-Seeking in Rodents. Conditioned place preference (CPP) isa commonly used task in rodents in which preference for anenvironment is acquired through associative learning followingpairing/s with drug exposure. Studies in humans have demon-strated that reward-paired objects, such as drug parapherna-lia, also elicit conditioned responses. However, the ability ofobjects to serve as conditioned stimuli has yet to be exploredin rodents, despite the greater stimulus control afforded by ob-jects versus environments. We present here initial findingsfrom a novel Conditioned Object Preference (COP) task, inwhich we measured the preference of adult rats for objectspreviously paired with cocaine or morphine administration. Wefirst measured investigation of test objects to establish base-line object preference which was followed by alternating salineand drug conditioning days. Rats were injected with saline ordrug (cocaine: 20mg/kg, intraperitoneal (ip); morphine: 10mg/kg,

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subcutaneous) and placed into the test chamber containingtwo copies of the same object. Different objects were usedfor saline versus drug conditioning sessions. When tested ina drug-free state, rats investigated the cocaine- or morphine-paired object significantly more than the saline-paired object,indicating acquisition of COP. Cocaine COP was then extin-guished via repeated testing without cocaine. Following ex-tinction, object preference returned to preconditioning levelsbut COP was reinstated with a priming dose of cocaine (10mg/kg, ip). In a final experiment, we conditioned animals inone chamber (chamber A) and tested them in a second cham-ber (chamber B). Following extinction in chamber B, cocaineCOP was still observed when animals were re-tested in cham-ber A, indicating “renewal” of COP. These findings demon-strate that, similar to environments, objects can elicit condi-tioned approach behavior through associative learning mech-anisms and that COP is amenable to the phenomena of ex-tinction, drug-primed reinstatement, and renewal. SUPPORT:University of Minnesota Grant-in-Aid

Kim, Earnest; Lattal, Matthew K. (Oregon Health & Sci-ence University) Amygdala Modulation of Cocaine-seekingBehavior. Persistent drug use despite harmful consequencesis a hallmark characteristic of addiction. Human and animalstudies have suggested that compulsive drug-seeking behav-ior to be the result of prefrontal cortical dysfunction and sub-sequent loss of “top down” inhibitory control of striatal circu-ity. However, it remains unclear how affective information overtime becomes disregarded with chronic drug use. Here we in-vestigate the role of the amygdala in compulsive drug-seekingbehavior using a rat intravenous self-administration model inwhich cocaine-seeking is procured at the risk of receiving mildfooshocks. Male Long Evans rats underwent cocaine self-

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administration training under a seeking-taking chain scheduleof reinforcement. Daily self-administration sessions consistedof a maximum of 30 trials. After one press on the seek leverand a variable interval (5 to 10 sec), one additional press re-sulted in a retraction of the seek lever and insertion of a takelever. Subsequently one take lever press resulted in an in-travenous cocaine infusion (0.89 mg/kg at rate of 0.088 mL/5sec). After >5 weeks of self-administration training, rats re-ceived 9 days of shock sessions in which 30% of the seeklever ended with a mild footshock (0.4 mA, 0.5sec). Shamrats quickly learned to suppress their drug taking and seekingresponses during shock. In contrast, animals with electrolyticlesion to the amygdala (BLA + CeA), continued to press bothtake and seek levers during punishment. These results sug-gest that amygdaloid processing is critical for compulsive drugseeking behavior and highlights the need to understand furtherhow “bottom up” limbic-cortical and limbic-striatal circuits con-tribute to the development of compulsive drug-seeking behav-ior. SUPPORT: NIH grants T32DA007262 and R01DA025922

Knox, Dayan; Stanfield, BrianaR; Staib, Jennifer; Keller,Samantha M; DePietro, Thomas. (University of Delaware)Using Measures of c-Jun Activity to Determine Mnemonic Pro-cesses Through which SPS Exposure Disrupts Extinction Re-tention. Single prolonged stress (SPS) is a rodent model ofpost traumatic stress disorder that leads to extinction reten-tion deficits. However, it is unknown if SPS disrupts extinctionretention by enhancing fear memory and/or disrupting extinc-tion memory. We previously attempted to use behavioral ma-nipulations to address this question, but the results of theseexperiments were inconclusive. In this study, we examinedmnemonic processes through which SPS exposure results inextinction retention deficits by assaying c-Jun levels in fear and

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extinction circuits after fear conditioning, extinction training,and extinction testing in SPS and non-stressed rats. Groups ofSPS and non-stressed rats were either fear conditioned (CS-fear) or presented with CSs in the absence of any footshock(CS-only). Subsets of rats were then euthanized after fearconditioning, extinction training, or extinction testing. A sepa-rate set of rats were euthanized after removal from their hous-ing colony in order to establish basal levels of c-Jun. c-Junlevels were measured in the medial prefrontal cortex (mPFC),dorsal hippocampus (dHipp), ventral hippocampus (vHipp), lat-eral amygdala (LA), and basal amygdala (BA). In replicationof previous studies, SPS induced extinction retention deficits.Preliminary findings suggest that SPS decreased baseline c-Jun levels in the Hipp. No changes in c-Jun levels during fearconditioning were observed with any of our treatments. Duringextinction training there were increases in c-Jun levels in themPFC of non-stressed rats, and this effect was attenuated inthe infralimbic region of SPS rats. SPS exposure also attenu-ated changes c-Jun levels in the Hipp and BA during extinctiontraining. While the study is ongoing, the results support thehypothesis that SPS-induced changes in c-Jun transcriptionalactivity in the mPFC, Hipp, and BA during extinction trainingcontribute to extinction retention deficits in the SPS model.SUPPORT: NIH COBRE grant - 1P20GM103653; UDRF grantawarded to D.K.

Koraym, Adam; Gallimore, Darci; Kidd, Tara; Dodd,Maria; Hennessy, Michael B.; Claflin, Dragana I. (WrightState University) Effects of Early-Life Stress and Social Buffer-ing on Learning in Juvenile Rats. It is well known that sep-aration from the mother can increase HPA activity and thepresence of the mother can reduce glucocorticoid levels inthe presence of stressors. Changes in glucocorticoids can, in

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turn, influence learning processes. The current study exam-ined the interaction between early-life stress and the presenceor absence of the mother on circulating corticosterone levels(Experiment 1). The impact of these effects on the develop-ment of subsequent learning processes were then assessedusing delay classical eyeblink conditioning (Experiment 2). In17-day-old rat pups, the absence of the mother greatly ele-vated glucocorticoid levels over a 60 minute period whereasthe presence of the mother suppressed this response. In Ex-periment 2 rat pups experienced 3 sessions of shock expo-sure on Day 17 and were randomly assigned to one of 3 so-cial manipulation groups. Immediately after each shock ex-posure session pups were either returned to the dam (socialbuffering), kept separate in a novel environment for 90 minutes(maternal separation), or returned to the dam for 45 minutesbut then separated for 90 minutes (delayed maternal sepa-ration). On Day 24, rats received 3 sessions of delay eye-blink conditioning. At this time they had undergone weaningon Day 21 and were individually housed. Preliminary datasuggest that acquisition of eyeblink conditioning for the ma-ternal separation and social buffering groups was not signifi-cantly different from a naïve control group that did not experi-ence any stressors at Day 17. However, the delayed maternalseparation group may have been facilitated in acquiring delayeyeblink conditioning. It appears that a second stressor dur-ing the early consolidation period may enhance acquisition.These data are discussed in terms of recent findings demon-strating improved cognitive performance following oscillationsin circulating glucocorticoid levels. SUPPORT: NIH/NIGMS,R25GM090122, IMSB BioSTAR and the Department of Psy-chology, Wright State University

Kwapis, Janine L.; Alaghband, Yasaman; Kramar, Eniko

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A.; Matheos, Dina P.; Rhee, Diane; Lopez, Alberto, J.; Wood,Marcelo A. (University of California, Irvine) HDAC3: An Epi-genetic Key to Ameliorating Synaptic Plasticity and MemoryDeficits in the Aging Brain. Aging is accompanied by cogni-tive impairments, including difficulty forming long-term mem-ories. Long-term memory formation requires gene expres-sion, a process that may be disrupted with age (Rowe et al.,2007; Berchtold et al., 2008). Epigenetic alterations (changesin gene expression that occur through alterations in chromatinstructure) may therefore contribute to age-related impairmentsin both gene expression and long-term memory. One majorepigenetic mechanism important for memory is histone acety-lation, in which acetyl groups are added or removed from hi-stone tails by acetyltransferases (HATs) or histone deacety-lases (HDACs), respectively. Increasing histone acetylation byblocking HDAC activity generally enhances both gene expres-sion and long-term memory. In particular, histone deacetylase3 (HDAC3) appears to be a key negative regulator of long-term memory formation, as blocking HDAC3 produces persis-tent object location memory following subthreshold training inyoung mice. Here, we tested whether HDAC3 activity alsocontributes to age-related impairments in long-term memoryand synaptic plasticity. First, we deleted HDAC3 in the dor-sal hippocampi of aging (18-month-old) mice before trainingthem in the hippocampus-dependent object location memory(OLM) task. As predicted, aging mice showed severe impair-ments in OLM. Deleting HDAC3 in the hippocampus rescuedthis deficit; aging mice lacking hippocampal HDAC3 showedrobust memory for OLM. We next tested whether HDAC3 alsolimits synaptic plasticity in the aging hippocampus. A singletrain of 5 theta bursts failed to produce stable LTP in slicesfrom 18-month-old mice, confirming that synaptic plasticity is

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also impaired with age. Blocking HDAC3 activity with a domi-nant negative mutant (HDAC3Y298H), however, amelioratedthis deficit, resulting in robust and stable potentiation. To-gether, these results indicate that HDAC3 is a key negativeregulator of both long-term memory and synaptic plasticity inaging mice. SUPPORT: NIH grants MH81004, MH101491,DA025922, DA036984, DA031989 to M.A. Wood and NIH T32AG000096-31 to J.L. Kwapis

Lacagnina, Anthony F; Drew, Michael R (University ofTexas at Austin) EnhancedContext FearMemory with SpacedContext Exposures. Contextual fear conditioning (CFC) is anassociative learning paradigm that requires an animal to forma mental representation of the surrounding context before anaversive stimulus may become associated with it. Theories ofCFC posit that such mental representations can be acquiredduring passive exploration of an environment and are essen-tial for conditioning, but make no predictions about how varia-tion in the temporal interval between context preexposure andconditioning will affect learning. Because the synaptic andanatomical substrates of memory change over time, we pre-dicted that the interval between context preexposure and con-ditioning would affect the strength of conditioning. We foundthat context preexposure 72h or 24h before single-shock CFCproduced higher conditioned fear than did preexposure 1minbefore or contiguouswith conditioning. Next we askedwhetherthe effect of preexposure timing was mediated through en-hanced fear acquisition or increased resistance to extinction.To do so, we tested whether variation in the timing of con-text preexposure affects sensitivity to postshock context ex-posure, a manipulation that potently extinguishes context fear.Again, increased preexposure-to-conditioning intervals wereassociated with higher freezing; however, the timing of context

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preexposure and postshock duration did not interact, suggest-ing that these manipulations independently affect the strengthof conditioning. We hypothesized that the superiority of 24hor 72h preexposure intervals relates to refinement of the hip-pocampal context representation during memory consolida-tion. To characterize the effect of preexposure interval on hip-pocampal context representations, we performed activity-dependentneural tagging using transgenic ArcCreERT2 mice. In sum-mary, CFC acquisition is enhancedwhen sufficient time elapsesbetween context preexposure and conditioning. We hypothe-size that CFC acquisition is enhanced when it involves reacti-vation of a consolidated context memory as opposed to simul-taneous acquisition of a context memory and a context-shockassociation. SUPPORT: NIH 5R01MH102595-02

Latsko, MaesonS.; Farnbauch, LaureA.; Jasnow, AaronM. (Kent State University) Enhanced juvenile glucocorticoidresponse is associated with an adult resistant phenotype fol-lowing juvenile social defeat. Adolescence is a critical devel-opmental period during which stress reactivity is exacerbatedcompared to adulthood, and when the experience of stresscan severely compromise appropriate adult stress responsive-ness. Targeting specific mechanisms underlying long-term ef-fects of early life stress is important yet challenging, given thesignificant individual variability in the response to stress. Tobegin to understand predictors of individual differences in re-sponse to social stress, we examine immediate and endur-ing effects of periadolescent social stress in mice focusingon identifying predictive markers and mechanisms underlyingtwo phenotypic behavioral responses that emerge as animalstransition into adulthood. Specifically, we subject periadoles-cent mice to a mild repeated social defeat paradigm followedby a social interaction test. We then examined the effects of

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periadolescent social defeat on social interaction at severaldevelopmental stages. We hypothesized that neurobiologicalmarkers and physiological responses to periadolescent socialdefeat stress may predict adult phenotypic responses to so-cial stress. One day following periadolescent social defeat,all mice display a resistant phenotype. When tested 8, 21,and 30 days later, two phenotypic responses emerge; mostmice display a susceptible phenotype, whereas a small per-centage remains resistant. Baseline and adult post-interactioncorticosterone levels were not associated with either pheno-type. However, mice that continued to display the resistantphenotype into adulthood had significantly elevated periado-lescent post-interaction serum corticosterone levels comparedwith mice that developed the susceptible phenotype and con-trol mice. These data suggest that the presence of elevatedcorticosterone during periadolescence may confer some pro-tection against the delayed effects of early life social defeat.These findings and future studies will help determine the roleof stress hormones on the ontogeny of differential response toadolescent social stress. SUPPORT: Farris Family Foundation

Laude, R. Jennifer; Fillmore, T. Mark (University of Ken-tucky) Activities Engaged in While Drinking Affect PerceivedIntoxication and Craving for Alcohol. The effect of experienc-ing a history of rewarding experiences while intoxicated on theappetitive properties of alcohol is a relatively unexplored areaof study. Such an experience could increase the rewardingproperties of the drug and result in escalation of use. Us-ing a sample of moderate to heavy drinkers, this study testedwhether experiencing a rewarding history while mildly intoxi-cated would increase the appetitive properties of the drug rel-ative to another condition in which a boring or mildly aversiveactivity occurred throughout the drinking episode. Drinkers

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were brought into the laboratory for two sessions, each on adifferent day. They were then assigned to either a placebo(0.0 g/kg) or active dose (0.47 g/kg) condition. In session one,participants consumed a beverage and then played stimulat-ing computer games (rewarding condition). During the sec-ond session, the same dose of alcohol received in sessionone was consumed but this time, a boring task was performed(non-rewarding condition). Changes in the subjective liking ofalcohol effects, craving for more of the drug, and perceivedintoxication were measured using a visual analog scale af-ter each treatment condition (rewarding vs. non-rewarding).Drinkers craved themost alcohol when they received the activedose and were playing stimulating games. They also felt moreintoxicated when engaging in a rewarding activity whether aplacebo or low dose of alcohol was consumed. The resultshave implications for the limited success of behavioral inter-ventions aimed at reducing drinking that fail to consider therole of the environment. SUPPORT: NIAAA F31AA023694and R01AA018274

Lee, Ji-Hye; Kimm, Sunwhi; Choi, June-Seek (KoreaUniversity) Effect of Emotional Trauma during Adolescenceon subsequent Aversive Memory Formation in rats. Psycho-logical trauma experienced during adolescence has lasting ef-fect on an individual’s emotional life. We developed an animalmodel of traumatic event during adolescence: a rat placed inan inescapable, donut-shaped maze was chased by a fast-approaching “bullying robot”. Effect of the trauma was exam-ined in two ways: specific memory formation and regulationof new emotional memory. Adolescent male Sprague Daw-ley rats were exposed to the trauma at postnatal day 33 to35. They received 20 trials per day for 3 days which consistedof a warning signal (5-s tone) and overlapped 2.5-s of being

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chased by the robot at every 15-20 second. After 3 weeks,animals were re-exposed to the context and tone to test mem-ory retention. Rats were also tested in the elevated-plus-mazeand received Pavlovian threat conditioning with 3 pairings oftone CS (20-s, 75 dB) and footshock US (1-s, 0.6-mA). Fol-lowing conditioning, memory tests for context and cue wereconducted. Additionally, rats received two sessions of extinc-tion and test for retention of extinction. We found that rats thathad experienced the initial traumatic event showed a higherlevel of fear response both to the context and the cue usedin the traumatic experience. In the elevated-plus-maze test,rats that had experienced trauma displayed reduced entriesto open arms. Rats that had received the trauma showed agreater level of fear response during fear conditioning. Theyalso showed increased fear response to the tone CS and theconditioning context. In addition, they showed retardation inthe subsequent extinction learning. Taken together, the cur-rent results suggest that the “bullying” robot is an effective newmethod for inducing traumatic stress using adolescent rats,which seems to up-regulates general anxiety and the forma-tion of aversive memory in subsequent emotional events, aswell as preserving the memory of initial trauma per se. SUP-PORT: NRF 2013M3C7A1056734

Lee, Yeon Kyung; Hong, Eun-Hwa; Kim, Sunwhi; Jie,Hyesoo; Choi, June-Seek Choi (Korea University) Uncon-trollable stress effects on discriminatory avoidance learning.Choosing an appropriate defensive response in the face ofdanger constitutes an important survival strategy. Two differ-ent types of behavioral paradigm, namely the active and pas-sive avoidance learning, have been employed to study braincircuits involved in learning of defensive response. However,little is known about defensive decision-making between the

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two conflicting responses. Here we used the discriminatoryavoidance learning (DIAL) in which two conditioned stimuli (CS1and CS2) signal the same aversive stimulus (footshock uncon-ditioned stimulus, US) but different types of avoidance are re-quired to rats. There is a strong clinical relationship betweenexposure to profound stress and deficits in adaptive behav-ior, and one of the key brain area modulating this relationshipis the medial prefrontal cortex (mPFC). In the previous study,we showed the lesion of mPFC in early phase of DIAL im-paired the discriminatory performance. In this experiment, weassessed the ability of rats to select appropriate defensive be-havior in threatening situations with two types of uncontrollablestress. In the first experiment, 14 rats (8 stress vs. 6 control)were trained in a shuttle box with CS1 (4 kHz, 10 s) that re-quires a “go” response and CS2 (500Hz, 10 s) that requires a“no-go” response. The rats trained 2 days of DIAL, and thenthey were exposed to restraint stress for next 4 days. After to-tal 6 days of training, both groups of rats showed equal levelof discriminatory responding. In the second experiment, 13rats (8 stress vs. 5 control) were exposed by cold water im-mersion stress. The results showed that the stress group wasimpaired in learning of discriminatory avoidance compared tothe control group. In sum, our data showed that DIAL is auseful paradigm for investigating how different responses areselected in aversive situations and that the different types ofstress interfere the process where the CS information must beutilized to select an optimal defensive response. SUPPORT:NRF-2013M3C7A1056734

Loh, Ryan; Galvez, Roberto (University of Illinois at Urbana-Champaign) Neocortical Kappa Inhibition Attenuates Forebrain-Dependent Associative Learning. There have been severalfindings indicating a primary role for the opioid receptor sys-

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tem in the modulation of learning and memory. Spatial tasks,fear conditioning, and y-maze spontaneous alternation haveall demonstrated that opioid modulation can impair task ac-quisition. The current literature investigating opioid effects inlearning and memory have focused on the mu-opioid recep-tor; however, several reports have indicated that there is alikely role for the kappa-opioid receptor in various behaviorallearning paradigms. We have recently demonstrated that sys-temic administration of the kappa specific opioid antagonist,NorBNI, prior to training delays acquisition for whisker-traceeyeblink (WTEB) associations in mice. In investigating thespecific brain region mediating this effect, it is well known thatprimary somatosensory neocortex (S1) is required for the ac-quisition and consolidation of the association. The followingstudy utilized intra-S1 injections of NorBNI with the behavioralparadigm WTEB to determine if the kappa-opioid receptor ismediating its learning induced effect through S1. In WTEB,animals are trained to associate whisker stimulation (CS) witha salient unconditioned stimulus (US) that causes an uncondi-tioned response. After several trials in which the CS is pairedwith the US, the animal begins to exhibit a conditioned re-sponse in anticipation of the US. Separating the CS and USwith a stimulus free trace interval makes this paradigm fore-brain dependent by recruiting higher brain structures such asthe hippocampus and most importantly, the neocortex. Thecurrent study utilized localized S1 injections of 10µg and 20µgof NorBNI paired with WTEB behavioral training. Local injec-tions of NorBNI significantly retarded learning relative to salinecontrols, suggesting that the kappa-opioid receptor is neocor-tically involved in the acquisition of forebrain-dependent traceassociative learning. Further research will focus on determin-ing the specific downstream effects of the kappa-opioid recep-

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tor that is mediating this effect in learning. SUPPORT: InternalLynch III, Joseph; Gray, Michael; Ouellette, Emily; Ad-

kins, Jordan; Winiecki, Patrick A.; Riccio, David C.; Jas-now, Aaron M.; (Kent State University) Estradiol-inducedFear Generalization is Blocked by Inactivation of NMDA orAMPA Receptors Prior to Retrieval . Generalization of fearresponses is a symptom of many anxiety disorders and wehave previously demonstrated that females generalize fear toa neutral context at a faster rate than males. This effect isdue in part, to activation of ERβ and modulation of memoryretrieval mechanisms resulting in fear generalization. Giventhat the effects of estradiol on fear generalization required ap-proximately 24 hours, our data suggested possible genomicactions on fear generalization. To determine whether theseactions were due to cytosolic versus membrane bound recep-tors, female rats were given infusions of ICI 182,780, a cytoso-lic estrogen receptor antagonist, into the lateral ventricle ordorsal hippocampus simultaneously with estradiol treatmentor with an ERβ agonist (DPN). Infusions of ICI into the dorsalhippocampus blocked the generalization induced by treatmentwith estradiol or DPN, suggesting that estradiol acts throughcytosolic ERβ. In a complimentary experiment, animals wereinfused with bovine serum conjugated estradiol (E2-BSA) totest the effects of membrane bound estrogen receptor activa-tion on fear generalization. E2-BSA infusions into the dorsalhippocampus did not induce fear generalization. Moreover,rats receiving intra-hippocampal infusions of the ERK/MAPKinhibitor, U0126, continued to display estradiol-induced gen-eralization, again suggesting that membrane-bound estrogenreceptors do not contribute to fear generalization. These datasuggest that estradiol-induced enhancements in fear gener-alization are mediated through activation of cytosolic/nuclear

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receptors. We hypothesized that estradiol induced fear gener-alization in the hippocampus through downstream enhancedglutamatergic signaling, Thus, in the final experiment, animalswere given peripheral injections of estradiol 24 hours beforea retention test and an infusion of low concentrations APV orNBQX into the dorsal hippocampus 5 minutes prior to testing.Infusions of either antagonist attenuated estradiol-induced gen-eralization, but had no effect on learning or generalization whenadministered alone, suggesting that estradiol-induced gener-alization is due, in part, to enhanced glutamatergic signaling.SUPPORT: Whitehall Grant; Farris Family Foundation

Murawski, Nathen J.; Asok, Arun (Center for Neuroscience,UC Davis (NJM); Department of Psychology and Brain Sci-ences, University of Delaware (AA)) Digital Context Fear Con-ditioning in Rats: Utilizing LCD-Based Visual Context Manipu-lations During Conditioning. Contextual fear conditioning (CFC)is a powerful behavioral assay for examining the neurobiologyof learning and memory. The simple behavioral setup and ro-bust long-lasting memories formed during conditioning havemade CFC an ideal paradigm for incorporating methodolog-ical innovations in behavioral neuroscience. CFC is highlycontext-specific in that higher levels of conditioned freezingare observed when training and testing occur in the same,versus a different, context. Typically, one context is made dis-tinct from another by manipulating one or more sensory fea-tures of a context (e.g., visual). Developing new methodolo-gies to systematically alter contexts can improve experimentalcontrol over context features and help better identify the neu-ral substrates that support CFC. We examined if adult malerats show the context pre-exposure facilitation effect (CPFE)by altering visual information provided by four LCD screenssurrounding a chamber. Rats received context pre-exposure

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on Day 1, an immediate 1.5 mA foot shock on Day 2, and acontext test on Day 3. Rats were pre-exposed to Context Aor B on Day 1. Context A and B only differed in the visualimage projected onto the LCD monitors. Controls includedrats pre-exposed to a distinct context and those without pre-exposure. Immediate shock and context test occurred in Con-text A. Rats pre-exposed to Context A showed the CPFE withsignificantly higher levels of freezing compared to controls.Rats pre-exposed to Context B failed to show the CPFE, withfreezing that did not differ significantly from any group. The re-sults suggest that 1) visual features contribute to CFC in ratsand that 2) visual components of the context can be paramet-rically controlled via LCD screens. Quantitative control andtemporal precision of contextual features afforded by digitalcontext presentations can greatly aid researchers in their un-derstanding of discriminating and generalizing fear to aversivecontexts. SUPPORT: 1 R01 HD075066-01A1 (ME Stantonand JB Rosen, University of Delaware)

Noble, J. Lindsey; Gonzalez, Ian J; Ngo, Tiffany T, Mal-hotra, Simran; Meyers, Eric; Bleker, Nathaniel, Carrillo,D’angeliqueD; Ramananthan, Karthik R; Rennaker, RobertL; Kilgard, Michael P; McIntyre, Christa K* (The Univer-sity of Texas at Dallas) Vagus Nerve Stimulation EnhancesExtinction of Conditioned Fear in an Animal Model of PTSD.Trauma-related disorders, such as posttraumatic stress disor-der (PTSD) are typically treated with cognitive behavioral ther-apy (CBT), as failure to extinguish conditioned fear is a coresymptom. Exposure therapy is a form of cognitive behaviortherapy where patients are repeatedly exposed to the cues thatelicit maladaptive conditioned responses. After repeated ex-posures to conditioned cues in the absence of reinforcement,conditioned responses should be extinguished. However, in

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humans with PTSD this often is ineffective. An adjunct ther-apy that could be administered with CBT to increase the effec-tiveness of the therapy would be beneficial. Optimal adjunctsshould enhance memory consolidation, as extinction learningrequires memory formation, while reducing anxiety to the stim-uli presented during therapy. Vagus nerve stimulation (VNS) isan FDA-approved treatment for the prevention of seizures. Re-cent research indicates that VNS can enhance memory con-solidation in rats and humans, and research from our lab hasshown that VNS can enhance fear extinction in healthy an-imals. Additionally recent research from our lab shows thatVNS can reduce anxiety. This evidence suggests that VNShas the rare combination of effects that are needed in an ad-junct to CBT. The single prolonged stressor (SPS) is an animalmodel of PTSD that exhibits many symptoms of PTSD seen inhumans, including failure to extinguish conditioned fear. Thepurpose of these experiments is to determine if VNS adminis-tered during extinction can enhance extinction learning, evenin a population that is resistant to fear extinction. We havefound that VNS-paired extinction not only enhances extinc-tion in SPS-treated animals vs. SPS-treated animals receivingsham stimulation during extinction, but also enhances extinc-tion to the same level as controls not subjected to SPS. Theseresults suggest that VNS could be effective as an adjunct toCBT. SUPPORT: NIH MH0869600101A1, DARPA

Ouellette, B. Emily; Lynch III, F. Joseph; Riccio, C. David;McEwen, S. Bruce; Jasnow, M. Aaron (Kent State Univer-sity) Corticosterone Attenuates Context Fear Generalizationin Male Rats. A characteristic of many anxiety disorders, in-cluding PTSD is generalization of fear responses to neutralstimuli. A counterintuitive feature of PTSD is that individualswith lower cortisol levels tend to be more susceptible to de-

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velop the disorder. Recent evidence in rodents suggests thatadministration of corticosterone protects against the delayedbehavioral and cellular effects of acute restraint stress. Giventhese data, we wanted to see if the administration of corticos-terone would also attenuate fear generalization. We assessedthe effects of corticosterone administration on fear generaliza-tion by training male Long-Evans rats in passive avoidance,and injecting them with 25 mg/kg of corticosterone or vehicleeither 30 minutes prior to, or 30 minutes following training. An-imals were then tested 14 days later in either the training con-text or a neutral context. Animals that were given pre-traininginjections of corticosterone displayed significant fear general-ization. However, rats receiving post-training injections of cor-ticosterone displayed significantly attenuated fear generaliza-tion compared to rats receiving vehicle control. These datasuggest that increased corticosterone during the consolida-tion period may help enhance memory precision for contextand attenuate fear generalization. These data have particularrelevance to PTSD, as they are consistent with recent reportsof protective effects of glucocorticoids on behavioral and cellu-lar symptoms triggered by traumatic stress. SUPPORT: HarrisFamily Foundation; Whitehall Grant

Pennington, Zachary T.; Avershal, Jacob Z.; Anderson,Austin S.; Fanselow, Michael S. (University of California,Los Angeles) Broadening the stress enhanced fear learning(SEFL) model: acute shock exposure augments subsequentstartle responses and contextual fear of a startle-paired con-text. Exposure to traumatic events is able to produce an en-during sensitization of several stress processes, among them,the acquisition of novel fear associations. Our laboratory haspreviously developed a model of this phenotype in which acuteexposure to 15 unsignaled shocks in one context subsequently

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increases fear of a novel CS paired with a single shock. How-ever, because both learning experiences utilize the same un-conditional stimulus (US), it has been unclear whether height-ened learning within this preparation is US-specific. Further-more, the extent to which this model captures other aspectsof the stress sensitization process has not been thoroughlyexplored. Here, we assessed whether the same 15 shockstressor we have traditionally used would similarly increasefear learning about a different US: an auditory startle stimulus.Open field activity was also assessed. Animals previously ex-posed to 15 shocks showed an increased auditory startle re-sponse and also displayed enhanced freezing in the context inwhich the startle stimulus was presented. However, these an-imals did not display altered open field activity. These findingsdemonstrate that enhanced fear learning in our model is notlimited to a single US, although general US processing maybe altered. Furthermore, these findings show that this modelcan simultaneously capture multiple phenotypes associatedwith traumatic experience. Lastly, this data demonstrates thatboth startle responses and freezing can be measured usingthe same automated, video-based, software. SUPPORT: NIHR01 #2R01MH062122-05A1 to MSF; NRSA 1F31MH108257-01 to ZTP

Pina, Melanie M.; Cunningham, Christopher L. (Ore-gon Health & Science University) Ethanol-Seeking Behavioris Expressed Directly through an Extended Amygdala to Mid-brain Neural Circuit. Drug-associated cues produce profoundpsychological and physiological effects, driving craving, drugseeking and ultimately relapse. Previous research has indi-cated that drug seeking is modulated by the bed nucleus of thestria terminalis (BNST) of the extended amygdala. Anatomi-cally, the BNST sends dense projections to the ventral tegmen-

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tal area (VTA), a midbrain region essential for motivation andreward. Behaviorally, disconnection of BNST from VTA hassignificantly attenuated cue-induced cocaine seeking, as mea-sured by conditioned place preference (CPP). Though indirect,this evidence suggests that a BNST-VTA circuit may under-lie cue-induced drug seeking. In the present experiments, weused selective manipulations to directly establish a role for theBNST to VTA neural circuit in cue-elicited ethanol seeking inadult male DBA/2J mice. An unbiased CPP procedure wasused, where ethanol (2 g/kg, IP) was paired with a distinct tac-tile cue and an expression (seeking) test was given 24 h afterthe final conditioning session. We used a retrograde intersec-tional strategy to drive expression of inhibitory designer recep-tors (hM4Di-DREADD) in an intermixed yet distinct subpopu-lation of BNST neurons that project to VTA. To selectively si-lence BNST-VTA neurons, hM4Di was activated by clozapine-N-oxide (CNO; 10 mg/kg, IP) injection 30 min before the CPPtest. Silencing of BNST-VTA neurons by CNO blocked ethanolCPP expression. Control studies showed this was not dueto CNO or viral infection alone, as CPP was not affected invehicle-administered hM4Di mice or CNO-treated GFP mice.Our findings suggest that a BNST-VTA projection is critically in-volved in ethanol seeking, as indexed by CPP. Moreover, ourwork complements and expands upon previous findings andprovides novel evidence for a direct BNST input to VTA in cue-induced ethanol seeking. With the existing literature, thesestudies indicate that BNST and its VTA projections are promis-ing targets for treatments directed at reducing craving and re-lapse. SUPPORT: NIH-NIAAA R01AA007702; Vertex ScholarAward; OHSUBrain Institute Fellowship; APADissertation Re-search Award; Psi Chi Graduate Research Grant; N.L. TartarTrust Fellowship

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Pisansky, Marc T.; Gewirtz, Jonathan C. (University ofMinnesota - Twin Cities) Intranasal oxytocin enhances so-cially transmitted fear behavior in mice. Oxytocin is an evo-lutionarily conserved neuropeptide implicated in social cogni-tion processes. The oxytocin system is dysregulated in psychi-atric diseases characterized by impaired social cognition (e.g.,autism, schizophrenia), and intranasal oxytocin enhances emo-tional recognition (a component of “empathy”) in both normaland psychiatric populations. In order to investigate the neu-robiological effects of oxytocin on social cognition, we havedeveloped paradigms for measuring socially transmitted fear,in which an observer mouse views a demonstrator mouse un-dergoing Pavlovian fear conditioning. Observer mice exhibitfreezing or escape, and—importantly—these fear behaviorsoccur more robustly when the observer-demonstrator pair arefamiliar (i.e., siblings) with one another. We hypothesized thatoxytocin would enhance socially transmitted fear behaviors.Therefore we administered oxytocin intranasally (20µg/kg) tonon-sibling observer mice using both acute (1 day) and sub-chronic (5 days) regimens. Compared to saline controls, sub-chronic oxytocin-treated observer mice exhibited significantlymore freezing (during) and escape (on the day following) con-ditioning of demonstrator mice. Observer freezing behavioralso correlated with demonstrator distress vocalizations recordedduring conditioning, but only for oxytocin-treated observermice.Acute administration of oxytocin 30mins prior to conditioninghad no effect on freezing. These data suggested that sub-chronic intranasal oxytocin produced neuroadaptive changes,perhaps in endogenous oxytocin signaling mechanisms. Totest this hypothesis, we conducted quantitative PCR analysesof oxytocin receptor (OXTR) expression in observer mousebrain tissue. Although unaffected in the anterior cingulate cor-

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tex, an area associated with the affective component of painprocessing, expression of OXTR mRNA was significantly re-duced in the amygdala of oxytocin-treated observer mice. Thisstudy elucidates one mechanism by which intranasal oxytocinenhances social cognition and therefore promises to contributeto our understanding of psychiatric diseases in which theseprocesses are compromised.

Pizzimenti, Christie; Lattal, K. Matthew (Oregon Health& Science University) Context-independent effects of shockon drug-seeking. Even following long periods of abstinenceindividuals with anxiety disorders have high rates of relapseto drugs of abuse. Many current models of relapse examinestressful experiences that occur in close temporal and physical(i.e., within the same context) proximity to the reinstatementtest. Therefore, little is known about how potentially stress-ful or fearful experiences in other contexts can cause persis-tent changes in drug-seeking behavior. In three experimentswe examined the effects of fear conditioning in one contexton drug-seeking for methamphetamine in another context. InExperiment 1, animals were trained to self-administer intra-venous methamphetamine, followed by extinction. Animalsthen received either a battery of 15 shocks in a distinct en-vironment or exposure to that context only. Twenty-four hourslater animals received a single shock in the self-administrationcontext, and while this failed to produce reinstatement, ani-mals that received a battery of shocks the day before frozesignificantly more than controls. In Experiment 2 the battery ofshocks was administered during acquisition of self-administration.Animals that received shock reinstated significantly more thancontrols to drug-associated cues and took significantly longerto extinguish lever pressing following drug-cue-induced rein-statement. In Experiment 3 the battery of shocks were ad-

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ministered before acquisition of self-administration. Animalsthat received shock lever pressed for methamphetamine sig-nificantly more than exposure only controls during acquisition.In a separate group of animals, the battery of footshocks wasalso shown to significantly elevate plasma levels of corticos-terone relative to exposure only controls to levels that are con-sistent with physiological stress. Taken together, these resultssuggest that a history of fear conditioning may induce greaterrates of reinstatement to drug-related cues and confer resis-tance against extinction following reinstatement. SUPPORT:NIDA, R01DA025922; NIDA, T32DA007262

Pochiro, Joseph M; Goodfellow, Molly J; Lee, MichaelA; Lindquist, Derick H. (The Ohio State University) TraceFear Conditioning and Hippocampal NR2B-NMDA ReceptorSignaling in Adult Rats Administered Ethanol During the ThirdTrimester-equivalent Period. Modeling fetal alcohol spectrumdisorders (FASD) in rats, our lab administers ethanol (5 g/kg/day)over postnatal days (PD) 4 to 9, corresponding to the thirdtrimester ’brain growth spurt’. As adults, cognitive functionis assessed by trace fear conditioning (TFC), whose acqui-sition depends on a distributed forebrain circuit (Raybuck &Lattal, 2014). Interestingly, the dorsal hippocampus (DH), andNR2B-containing NMDA receptors, become necessary onlywhen the CS-US trace interval exceeds 5-10 sec (Chowdhuryet al. 2005; Gao et al. 2010). Consistent with such data,Dupont et al. (2014) found impaired TFC in FASD rats trainedwith a 15 but not 5 sec trace interval, whereas the expres-sion of phosphorylated ERK1/2—activated downstream of theNMDA receptor—was significantly reduced in CA1 and CA3neurons at both intervals. Immunoblot results also indicate theDH of FASD rats contains significantly fewer NR2A and NR2Bmembrane-bound subunits (Goodfellow et al., In press). Al-

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together, postnatal ethanol is hypothesized to disrupt NMDAreceptor signaling during TFC, limiting or perturbing the intra-cellular cascades required to consolidate new learning.

In the current study, adult (~PD70) rats were trained with 10CS-US pairings, separated by a 30 sec trace interval; over thenext two days freezing was measured during context and CSretention tests. Only during the trace interval, following toneCS offset, was freezing significantly reduced in FASD rats.During TFC, synaptic NMDA-gated calcium influx stimulatesCaMKII translocation and NR2B binding, activating plasticity-related signaling molecules essential to LTP maintenance andlong-term memory consolidation (Halt et al. 2012). A secondgroup of rats were therefore sacrificed 20 min post-training inorder to image (confocal, 60X) and quantify NR2B and phos-phorylated αCaMKII immunofluorescent signal intensity, nor-malized to Hoechst-stained cell counts, in areas CA1, CA3,and the dentate gyrus. Results will be discussed in termsof putative treatment group differences. SUPPORT: ABMRF,grant 60034780

Rafa Todd, Carolynn; Hafenbreidel, Madalyn; Otis, James,M.; Twining, Robert, C.; Mueller, Devin (University of Wis-consin, Milwaukee) Infralimbic NR2A-containing NMDA Re-ceptors are Necessary for the Reconsolidation of Cocaine Self-administration Memory. Addiction is characterized by high re-lapse susceptibility, which can be triggered by drug-associatedcues. Cue presentation results in retrieval of the original drug-cue memory that becomes labile and must be reconsolidatedback into long-term storage. Repeated unpaired cue presen-tation, however, induces extinction. Thus, cue-reactivity canbe reduced by blocking reconsolidation or facilitating extinc-tion. Systemic blockade of NMDA receptors (NMDArs) dis-rupts reconsolidation of drug-cue associations in a modified

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self-administration (SA) paradigm or extinction in a standardSA paradigm. To further characterize these processes, weexamined the effects of post-extinction injections of an NM-DAr antagonist (CPP) on drug seeking following SA. Rats ac-quired cocaine SA followed by extinction. Extinction consistedof four 45-min extinction sessions in which rats were adminis-tered CPP after each session. Extinction retention was thentested during a subsequent 90-min session. CPP treatmentdecreased lever pressing during subsequent extinction ses-sions, suggesting either disrupted reconsolidation or facilitatedextinction. Next, we targeted the infralimbic medial prefrontalcortex (IL-mPFC), a structure implicated in extinction. Usingthe same procedure, CPP infusions before or after four briefextinction sessions resulted in a similar reduction in lever press-ing across subsequent days. To determine the NMDAr sub-type involved, we infused either the NR2A-selective antagonistNVP or the NR2B-selective antagonist Ro25 after four 45-minextinction sessions. Similar to the effects of nonspecific NM-DAr blockade, blocking NR2A- but not NR2B-containing NM-DArs reduced lever pressing across subsequent days. Finally,to dissociate if blocking NR2A-containing NMDArs disrupts re-consolidation or facilitates extinction consolidation, NVP wasinfused into IL-mPFC after four 10-min reactivation trials orin the absence of behavioral testing. Memory retention wastested during a subsequent 90-min session, revealing that block-ing NR2A-containing NMDArs after memory reactivation re-duced lever pressing. Overall, these results indicate that block-ing NR2A-containing NMDArs in IL-mPFC disrupts reconsoli-dation of the original drug-cue memory rather than facilitatesextinction. SUPPORT: R01DA038042; University ofWisconsin-Milwaukee Graduate School

Rankin, Catharine H.; Giles, A.C., Ardiel, E. A., Yu, A.

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(University of British Columbi) Response Based Analyses ofBehavior Overlook Other Important Behavioral Changes: In-tegrating Habituation into Ongoing Behavior. Traditionally re-searchers who study habituation have focused on a single di-mension of the behavior (i.e., response probability or magni-tude). Our high throughput behavioural analyses of habitua-tion of two different responses for wild-type and mutant strainsof C. elegans have changed this view. First we have shownthat there are a number of independent components (habitu-ation rate and final level for probability, duration and speed)of habituation of the tap response that show different formsof plasticity and, for the most part, are mediated by differentgenes. In addition, for both tap and photoactivation of the ASHneurons the response does not occur in a vacuum- there arechanges in ongoing behavior that complement the responsedecrement. Interestingly, as some aspects of behavior decre-ment others appear to sensitize. When the changes in thecomponents of behavior are integrated it facilitates dispersalallowing the animal to move away from the area. This offers anew way to think about the role of habituation and sensitizationin the context of overall behavioral strategies. These findingsalso have implications for other response-based measures oflearning and memory. SUPPORT: NSERC grant #122216-2013

Reyes, Kyrie-Anne E.; Kudva, Priya S; Todd, Ryan P;Sorg, Barbara A. (Washington State University) Prazosindisrupts reconsolidation of appetitive and aversive behaviorin rats: discordance between behavior and ultrasonic vocal-izations. Reconsolidation of memory is the process wherebymemories are recalled (reactivated) and then become suscep-tible to disruption by certain pharmacological agents if they aregiven shortly after the memory is reactivated. In this study,

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we examined the effects of the alpha-1-adrenergic antago-nist, prazosin, for its ability to disrupt the reconsolidation of anappetitive memory (cocaine-induced conditioned place prefer-ence, CPP) and an aversive memory (fear conditioning). Us-ing a CPP model, we found that rats given prazosin imme-diately after memory reactivation did not show CPP for theircocaine-paired side 1 day or 1 week later compared with ratsgiven saline. In contrast, prazosin had no effect on CPP in ratsnot given memory reactivation, suggesting that prazosin pre-vented CPP memory reconsolidation. We also examined 50kHz (positive affective) ultrasonic vocalizations (50 USVs) as-sociated with the cocainememory. Contrary to the suppressedCPP in rats given memory reactivation + prazosin, the numberof 50 USVs was not different between treatment groups whentested 1 day after memory reactivation: 50 USVs were ele-vated in both groups on the cocaine-paired vs. saline-pairedside. In fear conditioning studies, rats given prazosin imme-diately after memory reactivation decreased freezing behav-ior 1 day and 1 week later compared with rats given vehicle.Prazosin had no effect on freezing in rats not given memoryreactivation, suggesting that prazosin prevented fear memoryreconsolidation. However, the number of 50 USVs was equallysuppressed in both treatment groups. Taken together, pra-zosin appears to disrupt the reconsolidation of both an appet-itive and aversive memory. The number of 50 kHz USVs didnot mimic the behavior for CPP or fear conditioning, indicatingthat its correlation with behavior is not straightforward. USVsmay be a more sensitive index of memory or of positive affectthan is motor output. SUPPORT: Washington State Initiative171 (Alcohol and Drug Abuse Research Program)

Robinson-Drummer, Patrese; Heroux, NicholasA.; Stan-ton, Mark E. (University of Delaware) Intra-dorsal Hippocam-

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pal antagonism of Muscarinic Acetylcholine receptors disruptsthe Context Preexposure Facilitation Effect. Cholinergic dys-function produced by neonatal alcohol exposure can be mit-igated by developmental cholinergic enhancement (Monk, etal., 2012, Hippocampus 22:1750–1757). This dysfunction alsocontributes to learning impairments in juvenile rats tested in avariant of context fear conditioning known as the context pre-exposure facilitation effect (CPFE) (Dokovna et al., 2013, Be-havioral Brain Research, 248:114–120). However the specificbrain regions subserving cholinergic effects on the CPFE dur-ing development are not known. Scopolamine, a muscarinicacetylcholine receptor antagonist, disrupts the CPFE in juve-nile rats, when administered systemically before preexposure,training and testing, or before any single phase alone (Dokovna,& Stanton, 2012, ISDP Abstract). The current experiment ex-tended these findings by locally infusing scopolamine into thedorsal hippocampus on the preexposure, training and testingday. On PD 31, one group of juvenile rats received bilateralinfusions of scopolamine (35µg) or PBS 10min before pre-exposure to the training context (Pre group) or an alternatecontext (Alt-Pre group). Twenty-four hours later, a second setof animals received infusions before receiving two immediate2s, 1.5mA shocks in the training context. Finally, 24hr aftertraining, a third set of animals received infusions 10min beforetesting in the training context. For all infusion days, the Pregroup given PBS exhibited significantly more fear to the train-ing context than the Alt-Pre group. However, Pre group an-imals given scopolamine were not significantly different fromthe Alt-Pre group. This finding illustrates a specific role of dor-sal hippocampal cholinergic function in contextual fear condi-tioning in juveniles. Enhancing hippocampal cholinergic func-tion may reverse deficits in the CPFE produced by neonatal al-

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cohol exposure. SUPPORT: NIH grant R01 HD075066-01A1to MES; Office of Graduate and Professional Education Grad-uate Scholarship

Rose, Jacqueline; Alfiler, Lauren K.; Pribic, MicaelaR. (Western Washington University) Pavlovian ConditioningProduced by Activating Two Identified and Distinct Neural Cir-cuits in C. elegans. Pavlovian Conditioning has led to sev-eral discoveries into mechanisms of learning and memory. Af-ter determining a stable alteration in behavior following stim-ulus pairing, researchers have been able to uncover brain re-gions, neural circuits and cellular mechanisms involved. Us-ing the C. elegans model, with its well-described nervous sys-tem that includes circuits between 302 identified neurons to-tal, we have been able to take the reverse approach, selectingUS and CS based on the known neurons activated by thesestimuli and then measuring an increase in responsiveness af-ter these mapped neural circuits are activated close togetherin time. To examine Classical Conditioning in C. elegans, amild mechanosensory stimulus (vibration of worm substrateproduced by a low-frequency, 100 Hz auditory tone) activat-ing the ’touch circuit’ served as the NS/CS. For the US, ex-posure to either UV or blue-wavelength light ( 450 nm) acti-vating the recently described ’light circuit’ was employed. C.elegans show reliable avoidance to UV and blue-wavelengthlight as their outer cuticle is transparent making them vulnera-ble to damaging light rays. When these stimuli were paired ina delayed pairing protocol (4 sec tone whereby US light onsetoccurs at a 2 sec delay), an increase in responsiveness wasseen to the CS (tone-alone) stimulus at two minutes after pair-ing. When no light is presented, a slight decrease in respond-ing to the tone-alone can be seen, similar to habituation. Earlydata suggest that increasing the number of pairings does not

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immediately increase the response to tone. Additional studiesare underway to test the possibility of ’circuit’ plasticity by de-termining if motor response activation or inhibition can becomeassociated to the tone-alone stimulus by pairing the activationof channelrhodopsin expressed in the excitatory, as well as in-hibitory, motor output neurons.

Sangha, Susan (Purdue University) AmygdalocorticalCircuitry Contributes to Discriminative Reward, Fear and SafetyLearning. Accurate discrimination of environmental cues pre-dicting reward, fear or safety is important for survival. Theamygdala, prelimbic and infralimbic cortices are implicated inregulating reward-seeking and fear behavior; however, no stud-ies have examined their roles in discriminating among reward,fear and safety cues. Using a discriminative conditioning taskthat includes presentations of a reward cue (paired with su-crose), fear cue (paired with footshock) and a compound fear+safetycue (no footshock) within the same sessions allowed us to as-sess the flexibility and precision of fear and reward-seekingbehaviors to these cues. Single unit recordings made in the ratbasal amygdala showed neurons discriminate among reward,fear and safety cues. One particular population of neuronsshowed a selective response to only the safety cue, demon-strating safety selective neurons in the basal amygdala. Lo-cal, reversible inactivations of the prelimbic or infralimbic cor-tex yielded differential results: inactivating the prelimbic cortexblunted discriminatory reward seeking whereas infralimbic cor-tical inactivation impaired discrimination between the fear andsafety cues. Together these results imply that the amygdalo-cortical circuitry contributes to precise discriminative reward,fear and safety learning.

Shipman, Megan L.; Trask, Sydney; Green, John T.;Bouton, Mark, E. (The University of Vermont) Inactivation

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of the Prelimbic Cortex Attenuates Context-Dependent Exci-tatory Operant Responding. In operant renewal, extinguishedoperant behavior can recover when tested outside the contextin which it was extinguished. Previous work (Eddy et al., sub-mitted) has shown that inactivation of the prelimbic (PL) regionof the medial prefrontal cortex (mPFC) by baclofen/muscimol(B/M) during testing attenuates renewal of an extinguished re-sponse when testing occurs in Context A (e.g., ABA renewal).One explanation for this attenuated renewal is that the PL mayplay a role in context-dependent excitatory responding (e.g.,Thrailkill & Bouton, 2015). Two experiments tested this predic-tion. In Experiment 1, rats learned to lever press for a sucrose-pellet reward. Once the behavior was acquired, animals re-ceived an infusion of either B/M or saline vehicle into the PLand were tested in the acquisition context, Context A, or adifferent context, Context B. Although both groups showed adecrement in responding in Context B (a typical context-switcheffect), inactivation of the PL decreased responding in ContextA relative to the vehicle controls. Given that PL inactivationdecreased behavioral control by the acquisition context, othertypes of renewal in which testing occurs outside the acquisitioncontext should not be affected by PL inactivation. Therefore, inExperiment 2, the same rats again responded for the sucrosereinforcer in Context A. Responding was then extinguished ina new context, Context C. Animals then received an infusionof either B/M or saline into the PL before being tested in theextinction context, Context C, or another context, Context D.As predicted, both groups showed ACD renewal that was un-affected by PL inactivation. A final test of ABA renewal verifiedthat the cannulae were still functional and replicated Eddy etal. (submitted). Rather than affecting renewal generally, in-activation of the prelimbic cortex attenuates ABA renewal by

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reducing context-dependent excitatory responding in the con-ditioning context. SUPPORT: NIH RO1 DA 033123 to MEB

Shors, Tracey J. ; Olson, Ryan; Brush, Christopher J.;Alderman, Brandon (Rutgers University) Mental and Phys-ical (MAP) Training: Combining Meditation and Aerobic Exer-cise Enhances Synchronized Brain Responses during ConflictMonitoring. Feelings of fear and anxiety can interfere with ourability to monitor and ultimately resolve conflict in our lives. Inthis study, we provided a clinical intervention known as MAPTraining which stands for Mental and Physical Training. The in-tervention was inspired by and translated from laboratory stud-ies that relate mental and physical training activities to neu-rogenesis in the adult hippocampus (Shors et al., Neurobiol-ogy of Learning and Memory, 2014). The intervention wasprovided to individuals who were either clinically depressed(n=23) or otherwise healthy (n=33). Participants engaged intwice-weekly sessions, beginning with 30 minutes of “mental”training with focused-attention silent meditation followed by 30minutes of “physical” training with supervised aerobic exerciseat a moderate intensity. Before and after MAP Training, EEGsand event-related potentials (ERPs) were recorded during theFlanker Test, as a measure of cognitive control during conflictmonitoring.

Before MAP Training, individuals with clinical depressiondisplayed less robust ERP responses (indexed by N2 and P3)during the flanker task when compared to healthy individuals(Alderman et al., Frontiers in Human Neuroscience, 2015). Af-ter 8 weeks of MAP Training, depressed individuals exhibitedsimilar responses to healthy individuals and these neurocogni-tive improvements were accompanied by significant decreasesin depressive symptoms, reflected by a nearly 40% decreasein scores on the Beck Depression Inventory (BDI; Alderman

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et al., submitted). These data suggest that MAP Training im-proves neural correlates of depression. Surprisingly, even healthyindividuals reported significantly fewer symptoms of depres-sion following MAP Training. Depressed individuals also re-ported fewer ruminations, as measured by the Rumination Re-sponse Scale (RRS), and less self-judgment as suggested byresponses to the Five FacetMindfulnessQuestionnaire (FFMQ).These data suggest that a combination of mental training withsilent meditation and physical training with aerobic exercisecan increase cognitive control processes during conflict mon-itoring, which may thereby improve mental states associatedwith depression while decreasing the rehearsal of fearful mem-ories of the past.

Slaker, Megan; Sorg, Barbara A. (Washington State Uni-versity) Perineuronal nets in the prefrontal cortex contributeto acquisition of drug-associated memory. Perineuronal nets(PNNs) are unique structures of extracellular matrix (ECM)that surround primarily fast-spiking, parvalbumin-containing,GABAergic interneurons. PNNs have been implicated in learn-ing and memory within the amygdala, hippocampus, and me-dial prefrontal cortex (mPFC). Removal of PNNswith chondroitinase-ABC (Ch-ABC) enhances extinction learning when removedfrom the amygdala, impairs context-induced reinstatement offear conditioning when removed from the hippocampus, andimpairs cue-induced reinstatement of fear conditioning whenremoved from the mPFC. Recent work from our laboratory in-dicates that Ch-ABC treatment in the prelimbic region of themPFC impairs acquisition andmaintenance of a cocaine-inducedconditioned place preference (CPP) memory. Accompanyingthis impairment was a decrease in the expression of c-Fos,an immediate early gene that corresponds to neuronal acti-vation, specifically within neurons surrounded by PNNs. The

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goal of this study was to investigate the role of PNNs within anadditional region of the PFC, the orbitofrontal cortex (OFC),on the acquisition of cocaine-induced CPP. The OFC is impor-tant for decisionmaking involving delayed reinforcement and isimplicated in compulsivity and craving that accompanies drugaddiction. Adult, male Sprague-Dawley rats were treated withCh-ABC in the OFC and trained for cocaine-induced CPP. Pre-liminary results indicate that rats treated with Ch-ABC showimpaired acquisition of CPP compared to rats treated with ve-hicle. Additional studies will need to verify these findings, andfuture studies will examine the role of PNNs within the OFCon the maintenance of a CPP memory. SUPPORT: NIHDA033404

Trask, Sydney; Bouton, Mark A., Carranza-Jasso, R.(The University of Vermont) Learning Not to Make the Re-sponse During Operant Extinction. In operant extinction, anoperant behavior decreases in strength or frequency when itis no longer reinforced. Historically, the main explanations ofoperant extinction have emphasized the loss of stimulus ormotivational support when the reinforcer is withdrawn. Herewe present evidence, however, that operant extinction involvesactively learning to inhibit the response. The experiments useda discriminated operant procedure in which rats were rein-forced for lever pressing or chain pulling in the presence ofa discriminative stimulus (S), but not in its absence. In oneexperiment, extinction of the response (R) in the presence ofS weakened responding in S, but equivalent extinction expo-sure to S without the opportunity to make R did not. In otherexperiments, rats learned to perform several different combi-nations of stimulus and response (S1R1, S2R1, S3R2, andS4R2). Extinction of a response in one stimulus (i.e., S1R1)transferred and weakened the same response, but not a dif-

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ferent response, when it was tested in another stimulus (i.e.,S2R1 but not S3R2). The transfer of response inhibition alsooccurred when S1 and S2 set the occasion for R’s associationwith different food reinforcers. The results suggest that the or-ganism needs to make the response in extinction to achieveeffective operant extinction, and that the response inhibitionthat results can inhibit the response when it is occasioned byother discriminative stimuli. SUPPORT: NIH RO1 DA 033123to MEB

Williams, Amy R.; Lattal, K. Matthew (OHSU) Effects ofAcute Ethanol Withdrawal on Extinction and Reconditioning ofFear. Memory can be affected by a variety of illicit substances,including alcohol. Research has shown that acute and chronicethanol use can either enhance or perturb memory processes.The alteration of memory by ethanol is particularly relevant toPost-traumatic stress disorder (PTSD), as alcohol use disorderis highly comorbid with PTSD. Previously research from ourlaboratory has shown that acute ethanol withdrawal (6 hr fol-lowing a single 4 g/kg i.p. injection of 20% ethanol) caused im-pairments in both strong and weak conditioning of contextualfear. The effect of acute ethanol withdrawal upon memory pro-cesses following conditioning remains unknown. Therefore,the focus of this research was to assess how acute ethanolwithdrawal affects extinction and reconditioning in a mousecontextual fear conditioning procedure. Acute ethanol with-drawal did not significantly affect the formation of either an ex-tinctionmemory or a reconditioningmemory relative to a salinecontrol, but there was an ordinal trend that acute ethanol with-drawal caused a loss of rapid reacquisition following recon-ditioning that has been demonstrated by ethanol naïve ani-mals. This suggests different effects of ethanol withdrawal onprocesses underlying the formation of initial conditioning, ex-

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tinction, and post-extinction reconditioning memories. Furtherstudy on the interaction of alcohol withdrawal and fear memorycould inform treatment and prevention of the overlap of thesetwo disorders. SUPPORT: NIDA DA025922; DOD W81XWH-12-2-0048; ARCSRoche Scholar; T32NIAAA 5T32AA007468-28

Talk AbstractsAlphabetical by first author. (Abstracts not available for allspeakers.)

Barrientos, RuthM. (University of Colorado Boulder) Neu-roinflammation in the Normal Aging Hippocampus: Causes,Effects, and Therapeutic Interventions. Neuroinflammation isa normal and adaptive response following challenging life eventssuch as infection, surgery, or injury. In normal aging, however,this neuroinflammatory response is exaggerated and prolonged,particularly in the hippocampus, causing greater susceptibil-ity to memory impairments in this population. Sensitized, orprimed, microglia have been identified as a primary source ofthis exaggerated neuroinflammatory response and appear tobe a hallmark of the normal aging brain. Dysregulation of theneuroendocrine system may be an important cause of normalaging-induced microglial sensitization, as regulating corticos-terone in the aged hippocampus prevents microglial sensiti-zation and the downstream inflammatory sequelae. Severalmechanisms bywhich long lasting elevations in pro-inflammatorycytokines in the hippocampus produce memory impairmentshave been described, and include impairments to long-termpotentiation (LTP), and blunting of brain-derived neurotrophicfactor (BDNF). Pharmacological, dietary, and behavioral (phys-

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ical exercise) therapeutic approaches have been effective atattenuating the sensitized microglial phenotype, the exagger-ated neuroinflammatory response following an insult, and thecognitive impairments that ultimately follow. SUPPORT: NIA028271

Baxter, Mark; Alvarado, Maria (Icahn School of Medicineat Mount Sinai; Yerkes National Primate Research Center andEmory University) Cognitive and Socioemotional Develop-ment After Postnatal Anesthetic Exposure. Exposure to gen-eral anesthesia early in life is associated with neurotoxicity andlong-term cognitive impairment in rodents. Combined with theobservation that humans that undergo surgical procedures be-fore the age of 4 years are at a greater risk of learning disabil-ities at school age, this raises the concern that general anes-thetics may cause enduring neurocognitive impairments in hu-mans. Nonhuman primate models are uniquely positionedto shed light on this question because of the protracted neu-ral and behavioral development of monkeys. We have beenstudying behavioral development in rhesus monkeys that wereanesthetized with the inhalation anesthetic sevoflurane as in-fants. These monkeys have impaired memory and alteredemotional behavior compared to controls. These findings con-tribute to concerns about the impact of anesthesia on cogni-tive development in humans, and establish a model system inwhich potential mitigating treatments for this unintended effectof anesthesiamay be studied. SUPPORT: NIHR01-HD068388

Bevins, Rick; Charntikov, Sergios; Pittenger, Steven;Swalve, Natashia; Barrett, Scott (University of Nebraska- Lincoln) Conditioned Enhancement of the Nicotine Rein-forcer. According to the World Health Organization, “No otherconsumer product is as dangerous, or kills as many people.Tobacco kills more than AIDS, legal drugs, illegal drugs, road

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accidents, murder, and suicide combined” (The Tobacco Atlas[p.36]). Approaches to drug addiction that include conditioningprocesses have led to important advances in our understand-ing of drug use in general, and nicotine dependence specifi-cally. These approaches typically treat nicotine as an uncon-ditioned stimulus. That is, the biological effects of nicotine (re-ward, psychomotor stimulation, cognitive enhancement, anal-gesia) enter into an association with stimuli that reliably co-occur with these effects (cigarette, throat irritation, situationalcues). Also of import, but far less studied, is the pharmaco-logical effects of nicotine serving as an interoceptive stimulusfor other reinforcing events such as peer acceptance, alcohol,work breaks, stress relief, etc. Consequently, over time a userdevelops a rich appetitive conditioning history with the inte-roceptive stimulus effects of nicotine. This acquired appetitivevalue likely contributes to the tenacity of the nicotine addiction.An important prediction from theories of conditioned reinforce-ment and incentive motivation is that an excitatory conditionedstimulus, nicotine in our case, should more readily support be-havior. In this talk, we will present a set of studies testingthis prediction. Using rats, we merge the discriminated goal-tracking task (interoceptive Pavlovian conditioning) with the in-travenous nicotine self-administration task (nicotine reinforce-ment). In each study, rats had nicotine repeatedly paired withintermittent access to sucrose. This excitatory interoceptiveconditioning history increased the later self-administration ofnicotine. This finding held whether the schedule of reinforce-ment was a CRF, a VR, or a PR; it also persisted in extinction.Further, this effect occurred at 0.01 and 0.03 mg/kg/infusion ofnicotine. Finally, control comparisons decrease the feasibilityof alternative accounts. SUPPORT: DA034389

Chamizo, Victoria D. (Universitat de Barcelona) Trying to

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Understand the Differential Use of Spatial Information in Maleand Female Rats of Different Age, Juveniles and Adults. Thereis good evidence that male and female rats often rely on dif-ferent cues to solve spatial problems. Males tend to use ge-ometric information while females use more visual features orlandmarks. The same claim has been made in the human lit-erature, while using a variety of tasks. Are there specific con-ditions or requirements that determine this differential use ofspatial information in males and females? Recent researchshows that this seems to be the case (Torres et al., 2014,Chamizo et al., 2014). However, the initial claims are not con-firmed with younger female rats (Rodríguez et al., 2013). Whyis this? Nick Mackintosh and I, working with rats, addressedthese issues in recent years. In my talk I will present a set ofchallenging experiments, unfortunately not all of them with hiscollaboration, each of them opening a new line of research. Itwas my privilege for 30 years to work in collaboration with Pro-fessor Mackintosh. I still wonder what I did to deserve such amagnificent gift!References:Chamizo, V.D., Rodríguez, C.A., Torres, I., Torres, M.N., &Mackintosh, N.J. (2014). What makes a landmark effective?:Sex differences in a navigation task. Learning and Behavior,42, 348–356. Rodríguez, Clara A., Chamizo, V.D., & Mack-intosh, N.J. (2013) Do hormonal changes that appear at theonset of puberty determine the strategies used by female ratswhen solving a navigation task? Hormones and Behavior, 64,122–135. Torres, M.N., Rodríguez, C.A., Chamizo, V.D., &Mackintosh, N.J. (2014). Landmark vs. geometry learning:Explaining female rats’ selective preference for a landmark.Psicológica, 35, 81–100.

Cunningham, Chris (Oregon Health & Science Univer-

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sity) Deconstructing the Elements of Context in PavlovianDrug Conditioning. Abused drugs are frequently paired withcontextual cues to gain a better understanding of the condi-tioned motivational processes that contribute to drug-seekingbehavior. Although such cues typically consist of elementsfrom several modalities (e.g., visual, tactile, spatial), relativelylittle is known about the associative control gained by these el-ements or possible interactions among them (e.g., overshad-owing, blocking). We have recently explored this issue in theconditioned place preference (CPP) procedure using an appa-ratus that allows independent manipulation of contextual ele-ments. Our studies compared control of CPP when tactile (T)and visual (V) cues were conditioned individually or in com-pound (TV). In all studies, male DBA/2J mice were conditionedwith ethanol (2 g/kg, IP) using an unbiased (counterbalanced)two-compartment CPP procedure. Contextual elements weremanipulated by varying the floor texture (grid vs. hole) and wallcoverings (stripes vs. dots). Results showed that both ele-ments acquired control of CPP after VT conditioning, but CPPwas generally stronger to T than to V, suggesting that T wasmore salient. However, there was no evidence of overshadow-ing since element tests after TV training showed CPP levelssimilar to those elicited by each element conditioned alone.Furthermore, compound tests after element training did notprovide evidence of summation, suggesting instead that per-formance was controlled largely by the T element. Finally, con-ditioning of V alone before TV conditioning failed to interferewith conditioning to T despite strong conditioning to V, indicat-ing an absence of associative blocking. Overall, these findingssuggest that the elements of static contextual cues do not in-teract in the same way as the elements of phasic conditionedstimuli commonly studied in other conditioning models, raising

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the possibility of a fundamental difference in the nature of stim-ulus control by such cues. SUPPORT: NIH/NIAAA AA007702

Drew, Michael R.; Bernier, Brian E.; Ayoub, A.; Kim,H.J.; Zemelman, B.V. (University of Texas at Austin) DentateGyrus Controls Extinction of Contextual Fear Memory. Re-search on fear extinction has focused primarily on tone-shockconditioning. Less is known about the neural circuitry medi-ating extinction of contextual fear, a distinct form of condition-ing that recruits both cortical and subcortical plasticity. Basedon previous studies implicating the hippocampal dentate gyrus(DG) in context fear acquisition, we used optogenetic and phar-macogenetic methods to assess the role of DG in context fearexpression and extinction. To rapidly and reversibly manip-ulate DG neural activity during distinct phases of training, re-combinant adeno-associated virus (rAAV) was used to expressoptogenetic or pharmacogenetic neural actuators in DG cellpopulations. Halorhodopsin (eNpHR3.0) was used for opto-genetic inhibition, and the Gs-DREADD GPCR (rM3Ds) wasused for pharmacogenetic excitation. Optogenetic inhibition ofdorsal DG during the context-shock pairing impaired contextfear acquisition. Silencing DG during repeated re-exposuresto the context without shock did not alter fear expression butattenuated fear extinction, suggesting that neural activity in DGis required for acquisition and extinction of context fear but notfor its expression. Enhancing plasticity and/or excitability ofdentate granule cells via rM3Ds during context re-exposure af-ter acquisition had no effect on expression of fear memory butled to a significant reduction in freezing during a subsequentdrug-free context test, suggesting enhanced extinction or im-paired consolidation. In summary, our data indicate that DGcontrols acquisition and extinction of context fear memory butis not required for expression of context fear or context fear

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extinction. DG may provide a teaching signal that supportsacquisition- and extinction-related plasticity in a downstreamregion. Furthermore, the data suggest that context fear extinc-tion recruits neural circuits partially distinct from those control-ling extinction of tone-shock associations. Whereas extinctionof tone-shock learning is mediated by plasticity in amygdalaand prefrontal cortex, our studies identify DG as a critical lo-cus for context fear extinction. SUPPORT: NIH MH102595

Esber, Guillem; Haselgrove, Mark; LePelley, Mike (CityUniversity of New York, Brooklyn College) Reconciling theEffects of Predictiveness and Uncertainty on Attention in As-sociative Learning. The study of attention in associative learn-ing has been dominated by two contrasting proposals. On theone hand, predictiveness theories such as that advanced byMackintosh (1975) state that organisms will pay preferential at-tention to stimuli that have reliably signaled important events inthe past. On the other hand, uncertainty theories such as thePearce-Hall (1980) model posit that organisms would be bet-ter served by attending to (and thereby learning about) stim-uli whose consequences are uncertain, such as novel or in-consistently reinforced stimuli. Although both proposals havereceived ample empirical support, they often make conflictingpredictions. Thus, the question remains whether predictiveness-and uncertainty-tracking attentional mechanisms coexist in thebrain as suggested by recent hybrid models or, rather, whethera common mechanism might reconcile the apparent paradoxin the data. Esber andHaselgrove (2011) proposed a predictiveness-basedmechanismwhich is able to account not only for predictiveness-but also for uncertainty-related attentional phenomena. Inter-estingly, a slight modification of the uncertainty-based modeladvanced by Pearce, Kaye and Hall (1982) is equally able toaccommodate both kinds of phenomena. Thus, an integration

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of the extant attentional evidence is possible in terms of eithera predictiveness- or an uncertainty-tracking mechanism. Therelationship between these mechanisms will be explored.

Escobar, Martha; Bhattacharya, Subhrajit; Bhattacharya,Dwipayan; Suppiramaniam, Vishnu (Oakland University; AuburnUniversity) Synaptic Plasticity Changes After Retrieval of Con-textual FearMemories. Retrieval of a previously-acquiredmem-ory renders it ‘labile’ until the memory is once again consoli-dated. Although much is known about the cellular processesthat underlie this reconsolidation process, little is known abouthow synaptic plasticity changes through the reconsolidationperiod. Using rats in a conditioned fear preparation, we inves-tigated changes in long-term potentiation (LTP) and depres-sion (LTD), as well as the associated changes in glutamatereceptor expression on a time-dependent manner through thereconsolidation period. Retrieval of the fear memory resultedin decreased LTP and increased LTD in the Schaffer Collateralpathway of the hippocampus, slowly recovering to control lev-els over a 7h period. Expression of N-Methyl-D-Aspartate re-ceptors (NMDARs) andα-Amino-3-hydroxy-5-Methyl-4-isoxazole-Propionic Acid receptors (AMPARs) changed alongwith fEPTPs.GluR1 and GluR2 subunits of AMPARs were downregulatedshortly after retrieval, but returned to control levels 4h after re-trieval. NR2B levels were above normal immediately after re-trieval, but decreased to control levels 4h after retrieval. LTP/LTDwere at control levels after retrieval if normal levels of GluR2were maintained or NR2B receptors were antagonized, whichwas accompanied by maintenance of the conditioned memorythrough an amnestic treatment. These results suggest thatretrieval-induced alterations of conditioned memories may bemediated by the interplay of GluR2/NR2B activity and their ef-fects on synaptic plasticity. SUPPORT: Auburn University In-

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ternal Grant ProgramFrick, Karyn (University of Wisconsin-Milwaukee) Neu-

ral Mechanisms Through Which Progesterone Regulates Hip-pocampal Memory. Although much recent attention has beenpaid to the role of sex steroid hormones in regulating memory,the vast majority of research has focused on estrogens. Pro-gesterone is a potent neurosteroid that can facilitate memoryformation on its own, yet little is known about the molecularmechanisms underlying the cognitive effects of this hormone.This talk will review data showing that intrahippocampal infu-sion of progesterone enhances object memory in a mannerdependent on activation of ERK, mTOR, and canonical Wntsignaling. In particular, the role of membrane and intracellularprogesterone receptors will be highlighted, as these discretetypes of receptors appear to employ different molecular mech-anisms to enhance hippocampal memory. SUPPORT: Univ. ofWisconsin-Milwaukee, Ellison Medical Foundation/AFAR, NIHAG022525

Guzowski, John; Lewandowski, Gail; Miyashita, Teiko;Czerniawski, Jennifer (University of California, Irvine) Cy-tokine Modulation of Hippocampal Circuit Activity and MemoryFunction. Cytokines—originally identified as signalingmoleculesof the peripheral immune system—can directly impact neu-ronal function and synaptic plasticity. At present, little is knownabout how cytokines modulate activity of neural circuits under-lying specific cognitive processes. With ever-increasing ev-idence implicating cytokines in cognitive dysfunction associ-ated with neurodegenerative and neuropsychiatric disorders,it is imperative to gain a deeper understanding of how cy-tokines alter neural circuit functions supporting cognition. Tothat end, we are studying the impact of acute neuroinflamma-tion on memory retrieval processes at behavioral, neural cir-

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cuit, andmolecular levels in young adult male rats. In these ex-periments, we use systemic injection of bacterial lipopolysac-charide (LPS; 150 micrograms / kg, i.p.) to cause transientneuroinflammation, which peaks at 6 hours post injection asdetermined by elevated levels of proinflammatory cytokinesin hippocampus and other brain regions. Recently, we haveshown that acute neuroinflammation preferentially disrupts re-trieval in contextual discrimination memory tasks, but not allhippocampus-dependent memory tasks (Czerniawski et al.,Brain Behav Immun, 2015). Moreover, such impairment incontext discriminationmemory is accompanied by altered neu-ronal ensemble activity in hippocampal CA3 and CA1 circuits,consistent with impaired pattern separation processes (Czer-niawski & Guzowski, J Neurosci, 2014). Ongoing experimentsdemonstrate that blocking microglia activation in LPS-treatedrats with the systemic injection ofminocycline attenuates proin-flammatory cytokine expression in hippocampus, rescues con-text discrimination memory retrieval, and restores hippocam-pal circuit activity. Moreover, local microinfusion of minocy-cline into the dorsal hippocampus of LPS-treated rats is suf-ficient to rescue context discrimination memory retrieval. Weare now using microarray and proteomic approaches to bet-ter understand the cellular and synaptic mechanisms alteredby cytokine expression that produces the disruption of patternseparation processes in hippocampus critical for contextualdiscrimination memory function. SUPPORT: R01 MH08930(JG); T32 AG00896 (JC); James L. McGaughChair in the Neu-robiology of Learning and Memory (JG)

Kim, Jeansok (University of Washington) Place and Timeof Fear. Fear is an adaptive mechanism evolved to influencethe primal decisions of foragers in ‘approach resource-avoidpredator’ conflicts. To survive and procreate, animals must

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attain the basic needs (such as food, water, shelter, mate)while avoiding the ultimate cost of predation. Consistent withthis view, ecological studies have found that predatory threatscause animals to limit foraging to fewer places and/or to re-stricted times in their habitat. However, the neural mecha-nisms through which animals alter their foraging location andtime when confronted with danger remain largely unknown. Iwill present data from two ‘ethological’ fear preparations indi-cating that the amygdala-coded fear stamps the psychologicalfear content onto the hippocampal representation of physicallocation, and that the time-specific fear can act as a non-photicentraining stimulus for the circadian system. The clinical im-plications of fear spatially and temporally organizing defensivebehavior to human fear disorders will be discussed. SUP-PORT: NIH MH099073

Knox, Dayan (University of Delaware) Examining the ef-fects of stress on fear extinction using the single prolongedstress paradigm. Recently, there have been attempts to sys-tematically examine the effects of stress on fear extinction. Anumber of studies have used established stress protocols orthe stress inherent during fear conditioning to examine this re-lationship. In this talk, I describe how the single prolongedstress (SPS) paradigm can be used to examine the effects ofstress on fear extinction. SPS refers to serial exposure to re-straint, forced swim, and ether. The effects of this acute stressprotocol are typically observed seven days later. SPS is differ-ent to other stress protocols in that it was designed to specif-ically mimic behavioral and neuroendocrinological effects ob-served in post traumatic stress disorder. To this end SPS en-hances fast negative feedback of the HPA axis, arousal, glu-cocorticoid receptor (GR) levels in the hippocampus, and de-creases excitatory tone in the medial prefrontal cortex. When

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SPS is conducted prior to fear and extinction memory forma-tion, deficits in fear extinction retention are consistently ob-served, though the exact memory processes through whichthis occurs remains unknown (e.g. enhanced fear memory ordeficit in extinction memory). While it was initially thought thatenhanced GR expression and extinction retention deficits inthe SPS model are linked, recent research in my lab suggeststhat SPS-induced changes in GR function inhibits the extent ofextinction retention deficits in the SPSmodel. The observationthat SPS exposure consistently induces extinction retentiondeficits suggests that SPS exposure must induce maladaptiveneurobiological effects that lead to this outcome. However,it would also appear that SPS exposure elicits neurobiologi-cal effects that counteract the maladaptive effects induced bySPS. In a more general sense, this raises the possibility thatacute stress can induce maladaptive effects that are offset byadaptive effects induced by the same acute stress. Put an-other, way acute stress can be dualistic in nature.

Malvaez, Melissa; Greenfield, Venuz y.; Ochoa, Jesus;Wood, Marcelo A.; Kennedy, Pamela J.; Wassum, Kate M.(University of California, Los Angeles) Histone Acetylationin the Dorsolateral Striatum Selectively Mediates the Forma-tion of Behavioral Habits. Considerable evidence suggeststhat instrumental behavior depends on two distinct learningprocesses; one cognitive, in which the relationship betweenactions and their consequences is encoded, and one habit-ual, involving the formation of stimulus-response associations.These processes rely on dissociable neural circuits, but be-yond this very little is known about the mechanisms requiredto form these associative memories. Given the recently as-cribed role for epigenetics in memory formation, we examinedthe role of one such mechanism, histone acetylation, in instru-

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mental learning. Rats were trained to lever press for a food re-ward and were administered the non-specific histone deacety-lase (HDAC) inhibitor sodium butyrate (NaB) immediately fol-lowing each training session. Following training, devaluationof the food outcome was used to probe cognitive versus ha-bitual control of instrumental behavior. Although both groupslearned the task, those rats treated with NaB showed insen-sitivity to outcome devaluation earlier in training than vehicle-treated rats, suggesting that HDAC inhibition potentiated habitformation. Insensitivity to degradation in the action-outcomecontingency was also observed and the potentiation of habitoccurred regardless of training schedule (i.e., random inter-val v. ratio). Systemic HDAC inhibition increased histone H4lysine 8 acetylation specifically in the dorsal striatum, a majorcomponent of the instrumental learning circuit. In follow-up ex-periments, selective modulation of HDAC3 activity in the dor-solateral striatum was found to be sufficient to modulate thesensitivity of instrumental action to devaluation. These dataidentify chromatin modification by histone acetylation as an im-portant mechanism in the development of stimulus-responseassociativememories. Moreover, the results suggest that HDACinhibition can potentiate habitual over cognitive instrumentallearning processes, a finding with important implications forthe therapeutic application of HDAC inhibitors. SUPPORT:NIDA; UCLA Life Sciences; UCLA Faculty Career Develop-ment Award

McGaughy, Jill A. (University of New Hampshire) Dochanges in Prefrontal Norepinephrine Transporter density acrossAdolescence influence the Development of Cognitive Controlin rats? Adolescence is a period of major behavioral and brainreorganization. Different aspects of cognitive control matureat different rates in humans and in rodent models of it. These

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different developmental trajectories are hypothesized to reflectregion specificmaturation within the prefrontal subregions. Con-verging evidence has shown that norepinephrine is critical toattentional set-shifting and some forms of distractibility. As aresult, we assessed two noradrenergic markers at early, mid-and late adolescence in five functionally distinct subregions ofthe rat prefrontal cortex. We found that the density of nore-pinephrine transporters (NET), but not dopamine beta hydrox-ylase (DBH), changed across adolescence in a regionally se-lective manner. The prelimbic cortex, which is critical to cog-nitive flexibility and the lateral orbitofrontal cortex, critical toresponse inhibition, showed higher levels of NET at early thanmid- to late adolescence. Additionally, we used a rat modelto study the effect of standard ADHD treatments, atomoxetineand methylphenidate on cognitive control during early adoles-cence. While both of these drugs act as norepinephrine re-uptake inhibitors, higher doses of atomoxetine and all dosesof methylphenidate also block dopamine transporters (DAT).Low doses of atomoxetine, selective for NET blockade, wereeffective at remediating cognitive rigidity found in adolescents.In contrast, methylphenidate improved performance in rats un-able to form an attentional set due to distractibility but was with-out effect in normal subjects. These data support the criticalrole of cortical noradrenergic maturation in cognitive controlthroughout adolescence. SUPPORT: R21MH087921

McNally, Gavan P. (UNSW Australia) Selecting dangersignals: Attention, CS associability, and fear learning. Mack-intosh described some of the important behavioural conditionsrevealing variations in the associability of stimuli with reinforce-ment, and also a theoretical approach to understanding these.Such issues remain fundamental in Pavlovian learning andhave important implications for understanding the neural cir-

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cuitries of fear learning. I will describe the results of severalexperiments, some inspired by and others directly ‘borrowed’from this tradition, attempting to understand the brain mecha-nisms for learned changes in attention to danger signals.

Meyer, Heidi C.; Bucci, David J. (Dartmouth College) Be-havioral and Neurobiological Substrates of Negative OccasionSetting During Adolescence. The ability to inhibit an inappro-priate response is an essential aspect of adaptive behaviorand one that is still developing during adolescence. Success-ful inhibition depends not only on motoric stopping behavior,but also on cognitive processes that include the detection anduse of environmental cues that signal that a response is in-appropriate. Here we present evidence that adolescent ratshave difficulty using a class of these cues, known as negativeoccasion setters, to guide behavior. Briefly, rats received tri-als in which a “target” stimulus was presented by itself andfollowed immediately by the delivery of food reinforcement.On other trials a “feature” stimulus was presented just beforethe target and on those trials food was not delivered. Ado-lescents required twice as many training sessions as adultsor pre-adolescent rats to exhibit more responding to the tar-get during reinforced trials than during non-reinforced trials.In a second set of studies we probed the behavioral underpin-nings of this delay and found that adolescents can learn thedual meaning of the target cue like adults, but cannot expressthat learning until they are at least 53 days old, which is whenthe prefrontal cortex is thought to reach maturity. Moreover,we found that although adolescent and adult rats exhibit sim-ilar rates of acquisition of Pavlovian approach behavior, ado-lescents experience difficulty learning a secondary inhibitorymeaning of same cue during extinction. Finally, we probed theneural basis for the delay in negative occasion setting using

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chemogenetics and found that temporarily silencing neuronalactivity in the prefrontal cortex of adult rats, while simultane-ously increasing activity in the nucleus accumbens, resulted inthe behavioral phenotype exhibited by adolescents. Together,the findings inform the nature of the behavioral and neural sub-strates that contribute to immature behavioral control in ado-lescents. SUPPORT: F31MH107138 and R01DA027688

Miller, Ralph R. (State University of New York at Bingham-ton) The Construct of Attention and Beyond: Homage to NJMackintosh. For 50 years, NJ Mackintosh (1935-2015) wasamong the world’s leading students of animal cognition. Heradically changed the way in which we think about attention,he formulated three important models of associative learning,he mentored several generations of notable researchers, andhe was the field’s foremost spokesman. I will discuss asso-ciability as a modifiable perceptual process and alternativelyas a modifiable orienting response. Five conversations withMackintosh over a span of 40 years will be described alongwith how they altered research and theorizing in my labora-tory. (1) The implications of cue-to-consequence effects forstimulus associability. (2) Two types of memory interference,one a function of recency between target training and the inter-fering event, and the other a function of the similarity in contentof the target association and interfering association. (3) Thedevelopment of the comparator hypothesis to address failingsof prevailing models such as Mackintosh (1975) and Rescorla& Wagner (1972). (4) Causal reasoning in rats (and by exten-sion, humans) as a bottom-up process. (5) Perception as alearning process as exemplified in inhibitory perceptual learn-ing. SUPPORT: NIH MH33881

*Parker, Linda A.; *Sticht, Martin A., *Limebeer, CherylL., *Rafla, BenjaminR., #Abdullah,RehabA., #Poklis, Justin

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L., @HoWinnie, +Niphakis, Michah J., +Cravatt, BenjaminF., @Sharkey, Keith A, #Lichtman, Aron H. (*University ofGuelph, #Virginia Commonwealth University, @University ofCalgary & #Scripps Institute, LaJolla) Endocannabinoid Reg-ulation of Nausea is mediated by 2-Arachidonoylglycerol (2-AG) in the Rat Visceral Insular Cortex. Manipulations that ele-vate the endogenous cannabinoids (eCBs), anandamide and2-AG, have previously been found to interfere with nausea-induced conditioned gaping (a selectivemeasure of nausea) inrats. Although the precise brain mechanisms underlying nau-sea have yet to be fully uncovered, the visceral insular cor-tex (VIC) appears to play a critical role in mediating its sensa-tion. In fact, the synthetic cannabinoid agonist, HU210 (Lime-beer et al 2012) and exogenous 2-AG (Sticht et al, 2015) haveboth been found to disrupt the establishment of lithium chloride(LiCl) induced conditioned gaping in rats following intra-VICadministration, suggesting an important role for the VIC eCBsystem. Therefore, to further investigate the nature of eCBsuppression of nausea we assessed whether pharmacologicalinhibition of eCB catabolic enzymes within the VIC interfereswith acute nausea-induced conditioned gaping. Moreover, wequantified VIC eCB levels following these manipulations, andassessed their effects on VIC neuronal activity using the func-tional activation marker, c-Fos.

Rats received bilateral intra-VIC infusions of: 1) the dualFAAH/MAGL inhibitor, JZL195 (10 µg); 2) the selective FAAHinhibitors URB597 (0.01 µg) or PF3845 (10 µg); or 3) the se-lective MAGL inhibitor MJN110 (2 µg) prior to receiving an in-traoral saccharin infusion and systemically administered LiCl.They were subsequently re-exposed to saccharin 72 hr laterin a drug-free taste reactivity test, in which conditioned gap-ing was assessed. It was found that an acute LiCl injection

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resulted in a selective increase in VIC 2-AG levels relative tosaline-treated control animals, whereas anandamide contentin the VIC remained unchanged. Furthermore, MAGL inhibi-tion selectively increased VIC 2-AG levels following systemicor intra-VIC administration of MJN110 and suppressed condi-tioned gaping, as did intra-VIC infusion of the dual FAAH/MAGLinhibitor, JZL195. On the other hand, FAAH inhibition follow-ing either systemic or intra-VIC administration of URB597 orPF3845 did not elevate VIC AEA levels, and neither compoundhad an effect on nausea-induced gaping. Lastly, MAGL inhibi-tion by MJN110 reduced LiCl-induced c-Fos expression in theVIC.

Taken together, these findings suggest that VIC eCB sys-tem modulation of nausea may be driven primarily by the lig-and, 2-AG. More over, manipulations selectively targeting 2-AG may have therapeutic potential in reducing nausea, likelyby reducing neuronal activation in this brain region during anepisode of nausea.

SUPPORT: NSERC: 92057 to LAP; CIHR: 334086 to LAPand KAS; NIH: P30DA033934, RO1DA032933 and P01DA009789to AHL and BFC.

Pattwell, Siobhan S; Liston, Conor; Jing, Deqiang; Ni-nan, Ipe; Yang, Rui R;Witzmun, Jonathan; Murdock, Mitchell,H; Casey, BJ; Deisseroth, Karl; Lee, Francis S. (Fred Hutchin-son Cancer Research Center ) Leveraging Dynamic Changesin Neural Circuitry During Adolescence to Persistently Attenu-ate Fear Memories . Fear can be highly adaptive in promotingsurvival, yet it can also be detrimental when it persists longafter a threat has passed. Malleability of the fear responsemay be most advantageous during adolescence when there isan increased prevalence to explore novel, potentially threat-ening environments. Two opposing adolescent fear-related

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behaviors—diminished extinction of cued fear and suppressedexpression of contextual fear—may serve this purpose, butthe neural basis underlying these changes is unknown. Us-ing microprisms to image prefrontal cortical spine maturationlongitudinally and retrograde tracing of neurons in prelimbicand infralimbic cortices across development, we delineate dy-namic BLA-hippocampal-mPFC circuit reorganization associ-ated with these behavioral shifts. Exploiting this sensitive pe-riod of neural development, we modified existing behavioralinterventions in an age-specific manner to attenuate adoles-cent fear memories persistently into adulthood by incorporat-ing combined contextual and cued extinction elements. Thesefindings may define a strategy for leveraging dynamic neuralchanges during adolescence to extinguish pathological fearsimplicated in anxiety and stress related disorders. SUPPORT:NIHHD055177; Behavior & Brain Research Foundation/NARSAD

Ryabinin, Andrey E.; Smith, Monique L; Hostetler Car-oline M, Heinricher Mary M, Ryabinin Andrey E. (OregonHealth & Science University) Mice transfer increased painsensitivity via olfactory cues. Social environment has a strongimpact on human behavior and pathological disorders. Earlystudies by Pavlov replicated this phenomenon in dogs by demon-strating that organism’s responses to environmental stimuli de-pend on social circumstances. Recent studies identified com-plex social behaviors in rodent species, including prosocialand empathy-like behaviors. These complex social behaviorshave the ability to affect the preclinical understanding of manypathological conditions, including chronic pain and alcohol usedisorders. Since chronic pain, alcohol dependence and socialbehaviors are interrelated, we examined pain during voluntaryalcohol drinking in adult male C57BL/6J (B6) mice. We foundthat withdrawal from voluntary alcohol drinking in B6 mice in-

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creased sensitivity to mechanical and chemical pain stimuli.Remarkably, we observed hypersensitivity not only in alcohol-withdrawn mice, but also in water-drinking “bystander control”mice housed in the same room. Additional experiments de-termined that this abnormal pain state is communicated to by-stander mice via olfactory cues within the bedding. The in-creased sensitivity in bystander mice did not generalize to alltypes of sensory stimulation, as it was not accompanied byincreased startle response or anxiety-like behavior in the ele-vated plus maze. However, the pain experience in bystandermice was accompanied by increased c-Fos expression in corti-cal areas known to contribute to pain and empathy in humans.Finally, we demonstrated that this phenomenon also gener-alizes to other hyperalgesic states, as evidenced by the so-cial transfer of morphine withdrawal-induced or inflammatorypain. These studies demonstrate that hyperalgesia induced bya variety of stimuli can be socially transferred to conspecificshoused in the same room, which leads to substantial concernsabout how we house and test our experimental animals. Fi-nally, these results suggest that social variables should becarefully considered when designing and interpreting animalexperiments. SUPPORT: NIH AA016647 and AA10760

Sharpe, Melissa; Killcross, Simon (Sharpe: PrincetonNeuroscience Institute, Princeton University/National Instituteon Drug Abuse, Baltimore ; Killcross:School of Psychology,UNSW, Australia) The Prelimbic Cortex Directs Attention To-ward Predictive Cues During Pavlovian Conditioning. The-ories of functioning in the prelimbic (PL) cortex are distinctacross aversively- and appetitively-motivated procedures. Inthe appetitive domain, the PL cortex is argued to use higher-order cues to modulate learning and performance when theexperimental circumstance changes. In contrast, the domi-

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nant theory in the aversive literature is that the PL cortex isimportant for generating responses to fearful cues. Here, wepresent data which demonstrates that the PL cortex uses acue’s predictive power to direct a preferential degree of at-tention towards the best predictors of an outcome in line withMackintosh’s (1975) attentional process. Using an aversiveovershadowing procedure, we demonstrate that this role of thePL cortex is necessary during the learning phase but not forthe expression of these fear associations once they have beenformed. In a second set of experiments, we demonstrate thatthe PL cortex is only recruited for fear expression when atten-tional modulation is required to resolve competition betweendiscrete and contextual cues (i.e. when competition betweencontextual and discrete cues is high). We interpret these dataas an example of the PL’s role in using higher-order informa-tion, here the associative history of a stimulus, to direct atten-tion towards the best predictors of an outcome to overcomestimulus competition. These data show that the role of thePL cortex in attention generalises across both appetitive andaversive procedures.

Sorg, Barbara A.; Slaker, Megan; Todd, Ryan P.; Black-top, Jordan M.; Zuloaga, Damian G; Raber, Jacob; Dar-ling, Rebecca A.; Brown, Travis E.; Churchill, Lynn (Wash-ington State University) Role of Perineuronal Nets in Cocaine-AssociatedMemory. Themedial prefrontal cortex (mPFC) playsa significant role in cognitive function and contributes to cocaine-seeking behavior in both humans and rodents. Exposure tococaine and cocaine-associated cues increases the activityof pyramidal output neurons from the mPFC. The activity ofthese neurons is significantly modulated by GABAergic, par-valbumin (PV)-containing, fast-spiking interneurons. The ma-jority of these interneurons are enveloped by unique struc-

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tures of extracellular matrix called perineuronal nets (PNNs)that are integral to the maintenance of many types of plastic-ity. Using a conditioned place preference (CPP) procedure,we found that removal of PNNs primarily within the prelim-bic (PL) region of the mPFC of adult male Sprague-Dawleyrats impaired the acquisition and reconsolidation of a cocaine-induced CPP memory. This impairment was accompanied bya decrease in the number of c-Fos-positive cells surrounded byPNNs. Following removal of PNNs, the frequency of inhibitorycurrents on mPFC pyramidal neurons was decreased, but fol-lowing cocaine-induced CPP, both frequency and amplitude ofinhibitory currents were decreased, suggesting that removalof PNNs may prevent some of the cocaine-induced changesin pyramidal neurons. Consistent with these findings, prelim-inary data indicate that repeated cocaine exposure increasesPV and PNN intensity in the PL mPFC. Previous work indi-cates that the increase of PV and PNNs intensity may repre-sent maturation of these interneurons that is associated withreduced plasticity. Together, our findings indicate that cocaine-induced plasticity is impaired by removal of PNNs in the PLmPFC and that repeated cocaine exposure may reduce plas-ticity of PV+/PNN+ interneurons in the PL mPFC. Our stud-ies suggest that PNNs may be a therapeutic target for disrup-tion of cocaine CPP memories. SUPPORT: Supported by NIHGrant DA 030647 and DA033404 (BAS); NIDA T32DA007262(DGZ); NASA NNJ12ZSA001N (JR); and P30 GM 103398-32128 (TEB and RAD).

Stanton, Mark E. (University of Delaware) The Ontogenyof Learning in Context. This presentation briefly reviews thehistory and some key lessons of developmental studies of learn-ing as a context for the current symposium on adolescent cog-nition. It then describes recent developmental studies of the

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context preexposure facilitation effect (CPFE) in the rat. Thediscovery that rats show infantile amnesia—poor long-term re-tention of infant learning (Campbell & Campbell, 1962)—stimulatedrapid expansion of research on the ontogeny of learning. Theinitial goal to demonstrate learning at progressively youngerages (1970s–1980s) gave way to an interest in multiple mem-ory systems research (1990s–present) and in cognition thatdevelops at later ages, including adolescence (2000—present).Some key issues emerging from this history include continu-ity (or not) of development, ontogeny as a series of “ecologicalniches,” and the role of parameters, sensory-motor-motivationalprocesses, acquisition vs. expression, andmemory system in-teractions in the developmental emergence of learned perfor-mance. The main lesson is to never be surprised by anythingthat happens at any stage of development.

My colleagues and I have recently begun to study the on-togeny of the CPFE, a variant of contextual fear condition-ing in which (incidental) context learning on one day enablesconditioning to immediate shock on the next day (Fanselow,1990). We have found that the CPFE develops gradually be-tween postnatal day (PD) 17 and 24, at which point it de-pends on conjunctive learning of context features and on hip-pocampal NMDA receptors (Schiffino et al., 2011; Jablonskiet al., 2012). By early adolescence (PD31), the CPFE differ-entially drives prefrontal egr-1 expression on the training day(Asok et al, 2013; Schreiber et al., 2014); and long-term mem-ory of context learning increases during the adolescent pe-riod (Robinson-Drummer & Stanton, 2015). We are just be-ginning to learn how different processes and mechanisms ofcontextual fear conditioning develop from infancy through ado-lescence to adulthood. SUPPORT: NIH grant R01 HD075066-01A1

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Tronson, Natalie C. (University of Michigan) PersistentMemory Deficits and Histone Modifications after a SystemicInflammatory Event. Neuroimmune signaling is increasinglyidentified as a critical component in normal neural processesincluding learning and memory, and synaptic plasticity. Activa-tion of immune or inflammatory signaling in the periphery ro-bustly activates neuroimmune processes including microgliaand elevation in levels of cytokines in the brain, resulting inmodulation of synaptic function. Furthermore, inflammatoryevents includingmyocardial infarction, illness ormajor surgery,commonly lead to cognitive deficits and depression-like behav-ior lasting months or years after the event. Whereas acute ac-tivation of these processes has been the focus of many stud-ies, the mechanisms by which transient inflammatory eventscause persistent changes in cognitive function, memory andmood, remain unknown. Here we used a surgical model ofmyocardial infarction in mice to compare short- and long-termchanges in learning and memory after inflammation and de-termine the downstream mechanisms by which neuroimmunesignaling causes changes in memory formation that persistlong after resolution of inflammation. We observed impairedcontext fear conditioning 8 weeks following surgically inducedmyocardial infarction in both male and female mice, and thesealterations in memory processes persist beyond the durationof cytokine activity in the brain after MI. One candidate mecha-nism for mediating such effects is via epigenetic changes as aconsequence of cytokine-dependent signaling. We observeddysregulation of histone acetylation and phospho-acetylationin the hippocampus eight weeks after MI, although differentialmodifications were observed in males compared with females.These findings identify histone modification as one mecha-nism that may mediate lasting modulatory influence on mem-

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ory after a systemic inflammatory event, and suggest novel tar-gets for prevention and treatment of persistent cognitive deficitsafter MI, illness or major surgery. SUPPORT: NIH MH093459

Wiltgen, Brian (UC Davis) Retrieving memory with thehippocampus. The hippocampus is assumed to retrieve mem-ory by reinstating patterns of cortical activity that were ob-served during learning. To test this idea, we monitored theactivity of individual cortical neurons while simultaneously in-activating the hippocampus. Neurons that were active duringcontext fear conditioning were tagged with the long-lasting flu-orescent protein H2B-GFP and the light activated proton pumpArchT. These proteins allowed us to identify encoding neu-rons several days after learning and silence them with laserstimulation. When tagged CA1 cells were silenced, we foundthat memory retrieval was impaired and representations in thecortex (entorhinal, retrosplenial, perirhinal) and the amygdalacould not be reactivated. Importantly, hippocampal inactiva-tion did not alter the total amount of activity in most brain re-gions. Instead, it selectively prevented neurons that were ac-tive during learning from being reactivated during retrieval. Thesedata provide functional evidence that the hippocampus reacti-vates specific memory representations during retrieval. SUP-PORT: McKnight Memory & Cognitive Disorders Award

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Women in Learning (WIL)For the support and advancement of women in science.

Women in Learning (WIL) provides a forum in which students and post-docs inthe field of Learning Theory, Behavior, Memory and Neuroscience can seekadvice, support, and guidance on the advancement of female researchers froma notable female researcher who has already carved a path in the field. WIL isopen to anyone interested in supporting the advancement of women in science.

5th Annual Luncheon:Picnic House, Portland, OR

Saturday, September 1912:00 - 1:15 p.m.

Special Guest: Dr. Karyn Frick

For more information, visit www.womeninlearning.com.