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Animal Models of Animal Models of Gain ControlGain Control
in Schizophreniain Schizophrenia
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.Director, Tranlational Neuroscience ProgramDirector, Tranlational Neuroscience Program
[email protected]@upenn.edu
CNTRICS - CNTRICS - 04/22/2304/22/23
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
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• EEG - clinically relevant & foster preclincal translationEEG - clinically relevant & foster preclincal translation– Sensory systems - provide stimulus / input control Sensory systems - provide stimulus / input control – Evaluate neural response a stimulus - i.e. can assess gainEvaluate neural response a stimulus - i.e. can assess gain– Rodent equivalents to human measuresRodent equivalents to human measures
• Disease models - SchizophreniaDisease models - Schizophrenia– Pharmacological, endocrine, geneticPharmacological, endocrine, genetic
• Treatment modelsTreatment models– Examples of medication effectsExamples of medication effects
• Limitations:Limitations:– Averages vs. single trial analysisAverages vs. single trial analysis
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
Scope & framework for modeling gain controlScope & framework for modeling gain control
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• EEG - clinically relevant & foster preclincal translationEEG - clinically relevant & foster preclincal translation– Sensory systems - provide stimulus / input control Sensory systems - provide stimulus / input control – Evaluate neural response a stimulus - i.e. can assess gainEvaluate neural response a stimulus - i.e. can assess gain– Rodent equivalents to human measuresRodent equivalents to human measures
• Disease models - SchizophreniaDisease models - Schizophrenia– Pharmacological, endocrine, geneticPharmacological, endocrine, genetic
• Treatment modelsTreatment models– Examples of medication effectsExamples of medication effects
• Limitations:Limitations:– Averages vs. single trial analysisAverages vs. single trial analysis
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
Scope & framework for modeling gain controlScope & framework for modeling gain control
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Auditory Event Related PotentialsAuditory Event Related Potentials• EEG responses to sensory stimuli - evaluate the I/O functionEEG responses to sensory stimuli - evaluate the I/O function
• Mouse & human analogy for response properties & pharmacologyMouse & human analogy for response properties & pharmacology
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
S1 S2S1S2
5Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
ControlControl Schizophrenia Schizophrenia
• Original phenotype Original phenotype in unmedicated schizophrenia was reduced reduced S1 response amplitude S1 response amplitude - i.e. reduced gain (Adler, L.E. et. al., Biol Psych., 1986, Freedman, R., et. al. Biol. Psych. 1983; Jin, Y. et.al., Psych. Research 1997)
• Schizophrenia patients noted to have smaller visual ERP amplitude and less increase in amplitude with increasing stimulus intensity - i.e. reduced gain (Landau, S, et. al. Arch Gen Psych 1975)
Relevance to SchizophreniaRelevance to Schizophrenia
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Generation of human components
P50: Auditory thalamus and STG
N100: STG & other places
P200: Association auditory cortex Picton et al.,
Electroencephalogr Clin Neurophysiol. 1974
Human component qualities
P50 Increases amplitude 0.25-1 secAdler, L.E., et. al.
N100 Gating 0.5s, ISI 0.25-8 sec & Intensity dependence
Boutros, N., et. al. Psychiatry Res, 1999, Javitt, D., et. al. Clin Neurophys, 2000
P200 Intensity dependenceHegerl, U., et. al. Psychiatry Res, 1992
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
Rodent equivalents for human measuresRodent equivalents for human measures
Umbricht et. al, Brain Research 2004
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Human and Mouse overlay of Evoked Responses
-150
-75
0
75
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225
0 50 100 150 200 250 300 350 400 450 500Time
mV
-8
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mousehuman
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
P1
N1
P2
Mouse latency is 40% of that in humans Mouse latency is 40% of that in humans
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• EEG - clinically relevant & foster preclincal translationEEG - clinically relevant & foster preclincal translation– Sensory systems - provide stimulus / input control Sensory systems - provide stimulus / input control – Evaluate neural response a stimulus - i.e. can assess gainEvaluate neural response a stimulus - i.e. can assess gain– Validation of rodent equivalents to human measuresValidation of rodent equivalents to human measures
• Disease models - SchizophreniaDisease models - Schizophrenia– Pharmacological, endocrine, geneticPharmacological, endocrine, genetic
• Treatment modelsTreatment models– Examples of medication effectsExamples of medication effects
• Limitations:Limitations:– Averages vs. single trial analysisAverages vs. single trial analysis
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
Scope & framework for modeling gain controlScope & framework for modeling gain control
9
Disease ModelsDisease Models
•Ketamine - NMDA R antagonistsKetamine - NMDA R antagonists
•Corticosterone - stressCorticosterone - stress
•GGs transgenic mices transgenic mice
•AmphetamineAmphetamine
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
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Human 0 100 200 300 400 500 MSEC
Pre-attentive
CorticalActivation
StimulusEvaluation
Active AttentionalShifts
Task-Dependent Activity:
Salience detectionWorking Memory
SensoryPerception
StimulusStimulus
Mouse 0 40 80 120 160 200 MSEC
MMN
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
Consider N1 and MMN as examples of gain controlConsider N1 and MMN as examples of gain control
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Ketamine causes lasting reduction of initial response - i.e. GainKetamine causes lasting reduction of initial response - i.e. GainPattern similar for N40 & P80 at 3 & 5 weeks post treatmentPattern similar for N40 & P80 at 3 & 5 weeks post treatment
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
S1 S2
Sal
Sal
Ket
Ket
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Ketamine effects on deviance ERPs
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
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Ketamine Disrupts Deviance ERPs - MMNKetamine Disrupts Deviance ERPs - MMN
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
ControlControl KetamineKetamine
14Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
High dose Corticosterone used to model stress-induced High dose Corticosterone used to model stress-induced alterations in symptoms: Reduces S1 amplitude - i.e. Gainalterations in symptoms: Reduces S1 amplitude - i.e. Gain
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8.0 seconds
0.25 seconds
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
Corticosterone alters gain, not gatingCorticosterone alters gain, not gating
16Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
GGs mice show many endophenotypes of schizophrenia s mice show many endophenotypes of schizophrenia including deficits in spatial & associative learning as well as PPI including deficits in spatial & associative learning as well as PPI
• ABRABR• No differences in threshold - similar to schizophrenia No differences in threshold - similar to schizophrenia (Pfefferbaum, 1980)(Pfefferbaum, 1980)
• Wt & Tg differ in stimulus intensity response (p = 0.02) - i.e. gainWt & Tg differ in stimulus intensity response (p = 0.02) - i.e. gain
• N40N40
• Tg have smaller N40 amplitude than Wt - similar to schizophreniaTg have smaller N40 amplitude than Wt - similar to schizophrenia
• Tg have reduced N40 intensity functionTg have reduced N40 intensity function
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• Haloperidol eliminates Tg intensity function deficitHaloperidol eliminates Tg intensity function deficit
• Amphetamine approximates Tg intensity function deficitAmphetamine approximates Tg intensity function deficit
• Reverse translational question - Do patients differ on ABR Reverse translational question - Do patients differ on ABR and N100 intensity function? and N100 intensity function?
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
Haloperidol Amphetamine
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• EEG - clinically relevant & foster preclincal translationEEG - clinically relevant & foster preclincal translation– Sensory systems - provide stimulus / input control Sensory systems - provide stimulus / input control – Evaluate neural response a stimulus - i.e. can assess gainEvaluate neural response a stimulus - i.e. can assess gain– Validation of rodent equivalents to human measuresValidation of rodent equivalents to human measures
• Disease models - SchizophreniaDisease models - Schizophrenia– Pharmacological, endocrine, geneticPharmacological, endocrine, genetic
• Treatment modelsTreatment models– Examples of medication effectsExamples of medication effects
• Limitations:Limitations:– Averages vs. single trial analysisAverages vs. single trial analysis
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
Scope & framework for modeling gain controlScope & framework for modeling gain control
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Treatment & Translational ModelsTreatment & Translational Models
• Antipsychotics Antipsychotics
• Haloperidol & Olanzapine increase amplitudeHaloperidol & Olanzapine increase amplitude
• Drug-target evaluation using gain models - Drug-target evaluation using gain models - PDE4 inhibitorsPDE4 inhibitors
• Nicotine & nicotinic agonists alter S1 amplitudeNicotine & nicotinic agonists alter S1 amplitude
• Translational validity with vareniclineTranslational validity with varenicline
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
20Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
Olanzapine & haloperidol increase amplitude at long ISI Olanzapine & haloperidol increase amplitude at long ISI
no effects at short ISI - i.e. antipsychotics increase the gain no effects at short ISI - i.e. antipsychotics increase the gain of the system leading to an apparent change in gatingof the system leading to an apparent change in gating
**
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0
1
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3
4
Placebo Abstinent Placebo Smoking VareniclineAbstinent
VareniclineSmoking
mV
*
Nicotine & Varenicline increase S1 amplitude of Nicotine & Varenicline increase S1 amplitude of Human - Human - P50P50
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
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0
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Saline Nicotine Varenicline NicotineVarenicline
m V
Nicotine & Varenicline increase S1 amplitude of Nicotine & Varenicline increase S1 amplitude of Mouse - Mouse - P20P20
*
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
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Translational model of gain controlTranslational model of gain controlRolipram acts like an antipsychotic to increase S1 responseRolipram acts like an antipsychotic to increase S1 response
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
24
• EEG - clinically relevant & foster preclincal translationEEG - clinically relevant & foster preclincal translation– Sensory systems - provide stimulus / input control Sensory systems - provide stimulus / input control – Evaluate neural response a stimulus - i.e. can assess gainEvaluate neural response a stimulus - i.e. can assess gain– Validation of rodent equivalents to human measuresValidation of rodent equivalents to human measures
• Disease models - SchizophreniaDisease models - Schizophrenia– Pharmacological, endocrine, geneticPharmacological, endocrine, genetic
• Treatment modelsTreatment models– Examples of medication effectsExamples of medication effects
• Limitations:Limitations:– Averages vs. single trial analysisAverages vs. single trial analysis
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
Scope & framework for modeling gain controlScope & framework for modeling gain control
25Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
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Latency jitter hypothesis - low ITCLatency jitter hypothesis - low ITC Amplitude hypothesis - low signalAmplitude hypothesis - low signal
Several potential mechanisms to explain Several potential mechanisms to explain changes in amplitude on an averaged responsechanges in amplitude on an averaged response
Low amplitudeLow amplitude Low amplitudeLow amplitude
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Amphetamine
Saline
Haloperidol
Saline
Translational Neuroscience ProgramTranslational Neuroscience Program
Previous studies suggest increased latency jitter in schizophreniaPrevious studies suggest increased latency jitter in schizophreniaMouse amphetamine & haloperidol models suggest changes in single trial Mouse amphetamine & haloperidol models suggest changes in single trial
amplitude as wellamplitude as well
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
180 ms 700 ms
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Reduction of gamma ITC in Schizophrenia Reduction of gamma ITC in Schizophrenia previously shown by previously shown by Roach and Mathalon Schizophr Bull.2008; 34: 907-926
-400 -200 0 200 400 600
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Time (ms)
Pot
entia
l (m V
)
CS
Auditory Evoked Potential Phase-Locking Plotwavelet
decomposition
Penn subjects display reduced gamma PLF in schizophrenia n = 20/group (p < 0.04), consistent with previous findings
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
-50 0 50 100 150
-50 0 50 100 150
-50 0 50 100 150
-50 0 50 100 150
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NR1 hypomorphic Mice NR1 hypomorphic Mice have deficits in Gamma ITChave deficits in Gamma ITC
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
• 12% normal expression of NMDA R1
• social, self care, learning & memory impairments
• Reduction of PV interneurons related to generation of gamma oscillations
• However, ERP amplitudes are larger in NR1 hypomorphs - suggesting that gain and ITC are not entirely synonymous
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NR1 HypomorphsWild Type
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SummarySummary• Schizophrenia patients display a reduced relationship Schizophrenia patients display a reduced relationship
between stimulus intensity and response intensity for ERPs between stimulus intensity and response intensity for ERPs - i.e. reduced gain.- i.e. reduced gain.
• ERP data are often expressed as an average of multiple ERP data are often expressed as an average of multiple trials to a single stimulus, obscuring effects of latency jitter trials to a single stimulus, obscuring effects of latency jitter versus gain in single trialsversus gain in single trials
• May be helpful to evaluate intensity functions and single May be helpful to evaluate intensity functions and single trial data for S1 responses in schizophrenia.trial data for S1 responses in schizophrenia.
• Animal models can assess the potential determinants of Animal models can assess the potential determinants of reduced and increased gain control using highly translatable reduced and increased gain control using highly translatable EEG and ERP methodsEEG and ERP methods
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
30Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
Thank YouThank You
31
Ketamine disrupts deviance ERPs
**
** **
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
32
Gamma Activity & Intertrial Coherence
• Disrupted in schizophrenia & autismDisrupted in schizophrenia & autism• Rhythmic activity in 30 – 100 Hz rangeRhythmic activity in 30 – 100 Hz range
– Local coupling of neuronal assembliesLocal coupling of neuronal assemblies• Mechanism: synchronization of pyramidal Mechanism: synchronization of pyramidal
cells by fast-spiking interneuronscells by fast-spiking interneurons• Cognitive correlates, e.g. working Cognitive correlates, e.g. working
memorymemory• ITC - measure of EEG synchronization
with an external stimulus at a particular frequency = consistency of response
Stimulus Evoked Response
-50 0 50 100 150
-50 0 50 100 150
-50 0 50 100 150
-50 0 50 100 150
2
Trial1
3
4Phase
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
33
0.00
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NR1neo -/- WT
BaselineBaclofen
**
**
Use models for therapeutic development:Use models for therapeutic development:GABA Rescue of Gamma DeficitsGABA Rescue of Gamma Deficits
• Baclofen, selective GABAB agonist: rescues gamma PLF deficits in NR1neo-/-mice
* p < 0.02; ** p < 0.004
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
34
0.00
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NR1neo -/- WT
Ave
rage
30-
80 H
z IT
C
BaselineChlordiazepoxide
**
Use models for therapeutic development:Use models for therapeutic development:GABA Rescue of Gamma DeficitsGABA Rescue of Gamma Deficits
• Clordiazepoxide, non-selective GABAA positive modulator: reduces gamma PLF in both groups
* p < 0.02
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
35Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
Bupropion - indirect monoamine agonist & nicotinic antagonist Bupropion - indirect monoamine agonist & nicotinic antagonist Primary effects are on amplitude - only see the effects of Primary effects are on amplitude - only see the effects of
nicotine on gating with illness nicotine on gating with illness plusplus treatment in the model treatment in the model
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• Normal mouseNormal mouse
• Mouse on chronic bupropionMouse on chronic bupropion
• Mouse on bupropion + haloperidolMouse on bupropion + haloperidol
• Mouse on bupropion + haloperidol + Mouse on bupropion + haloperidol + nicotinenicotine
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
37
Medicated schizophrenia patients have abnormalities Medicated schizophrenia patients have abnormalities in gamma & theta oscillations in gamma & theta oscillations
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
38
Supplemental SummarySupplemental Summary• Intertrial coherence influences amplitude if ERPs, similar Intertrial coherence influences amplitude if ERPs, similar
to latency jitter, but is not the only factor involved.to latency jitter, but is not the only factor involved.
• Gating abnormalities may represent a mixed phenotype that Gating abnormalities may represent a mixed phenotype that results from a combination of reduced gain from the illness results from a combination of reduced gain from the illness and effects of medication.and effects of medication.
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
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Previous Post Docs:Previous Post Docs: Jenny Phillips, Ph.D. Jenny Phillips, Ph.D. Tobias Halene, M.D., Ph.D.Tobias Halene, M.D., Ph.D.
Previous Students:Previous Students:Jonathan KahnJonathan KahnDanielle TriefDanielle TriefSonalee MajumdarSonalee MajumdarMichelle MergenthalMichelle MergenthalJennifer FleisherJennifer FleisherJonathan AbelsonJonathan AbelsonJack KentJack KentDanit MayorDanit MayorKaren RudoKaren RudoJosh StillmanJosh StillmanJulia GlasserJulia GlasserWilliam BeckermanWilliam BeckermanNeal GhandiNeal GhandiRachel KleinRachel KleinSuzanne WilsonSuzanne WilsonOmid MotobarOmid MotobarCara Rabin Cara Rabin Jon TalmudJon TalmudSteve LuminaiseSteve LuminaiseJulie SistiJulie SistiChristina BodarkyChristina BodarkyRandal ToyRandal ToyViral GandhiViral GandhiKaren RyallKaren RyallJing-Yuan MaJing-Yuan MaJoe CrisantiJoe CrisantiStephen McKennaStephen McKennaAmar BainsAmar BainsXavier ReadusXavier ReadusLillia RodriguezLillia RodriguezJimmy SuhJimmy SuhJennifer Croner Jennifer Croner Rachel RosenbergRachel RosenbergJames WangJames WangMia WangMia WangMarcella ChungMarcella ChungKimia PourrezaiKimia PourrezaiVictoria BehrendVictoria BehrendPhilip SantoiemmaPhilip Santoiemma
StaffStaff::Yuling Liang, MDYuling Liang, MD
Post-DocsPost-DocsRobert Featherstone, PhDRobert Featherstone, PhDValerie Tatard, Ph.D.Valerie Tatard, Ph.D.
Graduate StudentsGraduate StudentsMike GandalMike GandalRobert LinRobert LinJohn SaundersJohn SaundersHiren MakadiaHiren Makadia
Undergraduate StudentsUndergraduate StudentsTony ThieuTony ThieuStefanie FazioStefanie FazioDheepa SekarDheepa SekarEric chuEric chuSarah DohertySarah DohertyMili MehtaMili MehtaYufei CaoYufei Cao
• NIMH, NIDA, NCINIMH, NIDA, NCI • Commonwealth of PACommonwealth of PA• SMRI, NARSADSMRI, NARSAD • NuPathe, AstraZeneca, LillyNuPathe, AstraZeneca, Lilly• ITMAT, Abramson Cancer CenterITMAT, Abramson Cancer Center
Previous Staff:Previous Staff:Mary DankertMary DankertFarzin IraniFarzin IraniChristina MaxwellChristina MaxwellKayla MetzgerKayla MetzgerPatrick ConnollyPatrick ConnollyBreanne WeightmanBreanne WeightmanWendy ZhangWendy ZhangDebbie IkedaDebbie IkedaJake Burnbaum. Jake Burnbaum. Chalon Majewski-Tiedeken.Chalon Majewski-Tiedeken.Noam RudnickNoam RudnickRichard EhrlichmanRichard EhrlichmanLaura AmannLaura AmannBrianna WeightmanBrianna Weightman
Steven J. Siegel, M.D., Ph.D.Steven J. Siegel, M.D., Ph.D.
Translational Neuroscience ProgramTranslational Neuroscience Program
CollaboratorsCollaboratorsBasic:Basic:
Steve Arnold, Konrad TalbotSteve Arnold, Konrad TalbotChang-Gyu Hahn, Greg Carlson Chang-Gyu Hahn, Greg Carlson Ted Abel, Diego ContrerasTed Abel, Diego ContrerasJulie Blendy, Ted BrodkinJulie Blendy, Ted BrodkinLief Finkel, M. LazarewiczLief Finkel, M. Lazarewicz
Clinical:Clinical:Raquel Gur, Ruben Gur, Bruce Turetsky - Raquel Gur, Ruben Gur, Bruce Turetsky -
NeuropsychiatryNeuropsychiatryCaryn Lerman, Andrew Strasser TTURCCaryn Lerman, Andrew Strasser TTURCTim Roberts & Chris Edger, CAR/CHOPTim Roberts & Chris Edger, CAR/CHOP