enhancement of auditory fear conditioning after housing in a complex environment is attenuated by...
TRANSCRIPT
Enhancement of auditory fear conditioning after housing in a
complex environment is attenuated by prior treatment with amphetamine
Lisa A. Briand, Terry E. Robinson and Stephen Maren
Lisa A. Briand, Terry E. Robinson and Stephen Maren
BackgroundBackground
Living in a complex environment increases: cerebral volume Dendritic spine density and number LTP Resistance to neural insult Synaptic connectivity
Living in a complex environment increases: cerebral volume Dendritic spine density and number LTP Resistance to neural insult Synaptic connectivity
BackgroundBackground
Hippocampal-dependent learning tasks affected by complex housing Morris water maze Hebb-Williams Maze
Pavlovian fear conditioning in mice
Hippocampal-dependent learning tasks affected by complex housing Morris water maze Hebb-Williams Maze
Pavlovian fear conditioning in mice
BackgroundBackground
Traditionally, cued fear is thought to be purely amygdala dependent and contextual fear, hippocampal and amygdala dependent.
Recently, the ventral hippocampus has been implicated in auditory fear conditioning.
Traditionally, cued fear is thought to be purely amygdala dependent and contextual fear, hippocampal and amygdala dependent.
Recently, the ventral hippocampus has been implicated in auditory fear conditioning.
BackgroundBackground Psychostimulants
Increase dendritic branching and spine density Regions implicated in behavioral sensitization
Block dendritic changes induced by complex environment Those changes that may be responsible for
learning and memory
Psychostimulants Increase dendritic branching and spine
density Regions implicated in behavioral sensitization
Block dendritic changes induced by complex environment Those changes that may be responsible for
learning and memory
PsychostimulantsPsychostimulants
Amphetamine increases dopamine in the synaptic cleft by acting as a false substrate for DAT
Amphetamine increases dopamine in the synaptic cleft by acting as a false substrate for DAT
VTA NAc
DA
GABA
GABA
VTA interneuron
Amphetamine&
Cocaine
Nicotine
+
Opiates
-
Ethanol (?)
-
QuestionsQuestions
Does a complex environment modulate learning in a Pavlovian fear-conditioning paradigm?
Does prior treatment with amphetamine modulate environmental effects on learning?
Does a complex environment modulate learning in a Pavlovian fear-conditioning paradigm?
Does prior treatment with amphetamine modulate environmental effects on learning?
DetailsDetails Sprague Dawley rats ♂ Housed for 3 months in
Individual plastic hanging cages (isolated) 20 x 23 x 20 cm
Groups of 3 rectangular plastic cages (social) 20 x 43 x 20 cm
Groups of 12 stainless-steel monkey cages (complex) 61 x 61 x 72 cm
Sprague Dawley rats ♂ Housed for 3 months in
Individual plastic hanging cages (isolated) 20 x 23 x 20 cm
Groups of 3 rectangular plastic cages (social) 20 x 43 x 20 cm
Groups of 12 stainless-steel monkey cages (complex) 61 x 61 x 72 cm
General MethodsGeneral Methods
Animals housed for 3 months in respective environments then housed in social/standard cages during tests
Day1 - Fear conditioning paradigm
Day2 - Contextual test
Day3 - CS test (auditory cue)
Animals housed for 3 months in respective environments then housed in social/standard cages during tests
Day1 - Fear conditioning paradigm
Day2 - Contextual test
Day3 - CS test (auditory cue)
Experiment 1Experiment 1
4 Pairings of tone (CS) with shock (US) 30 sec; 80 dB; 2 kHz 2 sec; 1 mA
Measured freezing (CR)
No statistical differences
4 Pairings of tone (CS) with shock (US) 30 sec; 80 dB; 2 kHz 2 sec; 1 mA
Measured freezing (CR)
No statistical differences
Experiment 1Experiment 1 CS alone elicits long-
term fear memory 6 min of tone (Black line)
Complex group shows prolonged freezing response
Difference due to complex environment rather than social housing
CS alone elicits long-term fear memory 6 min of tone (Black line)
Complex group shows prolonged freezing response
Difference due to complex environment rather than social housing
Experiment 1Experiment 1
Context alone does not elicit significant differences
Trend toward significance
Complex group may freeze more to context at later time points
Context alone does not elicit significant differences
Trend toward significance
Complex group may freeze more to context at later time points
ConclusionsConclusions
Housing in a complex environment facilitated Pavlovian fear conditioning
Effect of environment on conditioned fear was much stronger for auditory fear than contextual fear
Housing in a complex environment facilitated Pavlovian fear conditioning
Effect of environment on conditioned fear was much stronger for auditory fear than contextual fear
DiscussionDiscussion
Inconsistent with previous studies in mice (Duffy et al. ’01; Tang et al. ’01) Found equal effects of enrichment on
contextual and auditory fear Used single pairing of shock and tone
Species difference or methodological
Inconsistent with previous studies in mice (Duffy et al. ’01; Tang et al. ’01) Found equal effects of enrichment on
contextual and auditory fear Used single pairing of shock and tone
Species difference or methodological
DiscussionDiscussion
The isolated and socially housed animals may use additional time in the conditioning context to consolidate contextual fear memory
Whereas complex-housed animals may exhibit a ceiling effect
The isolated and socially housed animals may use additional time in the conditioning context to consolidate contextual fear memory
Whereas complex-housed animals may exhibit a ceiling effect
DiscussionDiscussion
Environmental complexity could modify the ventral hippocampus in a way that allows for the enhancement of cued fear while having only a slight effect on contextual fear.
Environmental complexity could modify the ventral hippocampus in a way that allows for the enhancement of cued fear while having only a slight effect on contextual fear.
Experiment 2Experiment 2
Robust behavioral sensitization pretreatment
21 consecutive days of amphetamine 4.0 mg/kg with intermittent doses of 0.5
mg/kg to measure extent of psychomotor sensitization
Robust behavioral sensitization pretreatment
21 consecutive days of amphetamine 4.0 mg/kg with intermittent doses of 0.5
mg/kg to measure extent of psychomotor sensitization
Experiment 2Experiment 2
Significantly more locomotion on day 21 than day 1 in response to amphetamine dose of 0.5 mg/kg
No difference in saline group
Significantly more locomotion on day 21 than day 1 in response to amphetamine dose of 0.5 mg/kg
No difference in saline group
Experiment 2Experiment 2
Divided into complex and “standard” cages (groups of 3) for 3 months after amphetamine N=12 for Complex Saline N=12 for Complex Amphetamine N=12 for Social Saline N=12 for Social Amphetamine
Divided into complex and “standard” cages (groups of 3) for 3 months after amphetamine N=12 for Complex Saline N=12 for Complex Amphetamine N=12 for Social Saline N=12 for Social Amphetamine
Experiment 2Experiment 2
CS alone elicits long-term fear conditioning
Complex/Saline group shows more robust freezing than all other groups
CS alone elicits long-term fear conditioning
Complex/Saline group shows more robust freezing than all other groups
Experiment 2Experiment 2
Contextual freezing
No differences between groups
Contextual freezing
No differences between groups
Experiment 3Experiment 3
Animals were moved to social housing (groups of 3) during the fear conditioning and testing in experiments 1 & 2
Experiment 3 simply left the complex housed animals in the same cage during testing
Animals were moved to social housing (groups of 3) during the fear conditioning and testing in experiments 1 & 2
Experiment 3 simply left the complex housed animals in the same cage during testing
Experiment 3Experiment 3
CS alone elicits long-term fear memory
Complex/saline group still shows more robust freezing response
CS alone elicits long-term fear memory
Complex/saline group still shows more robust freezing response
Experiment 3Experiment 3
Contextual Freezing No difference
Contextual Freezing No difference
ConclusionConclusion
Amphetamine attenuates cued fear conditioning in animals housed in a complex environment
Amphetamine attenuates cued fear conditioning in animals housed in a complex environment
DiscussionDiscussion Some research has shown that prior
exposure to stimulants limits structural plasticity associated with living in complex environment
Possibly, exposure to amphetamine blocked effect of complex environment to facilitate fear learning by limiting structural plasticity associated with living in complex environment
Some research has shown that prior exposure to stimulants limits structural plasticity associated with living in complex environment
Possibly, exposure to amphetamine blocked effect of complex environment to facilitate fear learning by limiting structural plasticity associated with living in complex environment
DiscussionDiscussion
An experiment with low doses methamphetamine prior to exposure to a complex environment showed more cortical weight than those without AMP
Low doses of amphetamine also improve recovery from brain injury and in conjunction with speech therapy, greater recovery from aphasia
An experiment with low doses methamphetamine prior to exposure to a complex environment showed more cortical weight than those without AMP
Low doses of amphetamine also improve recovery from brain injury and in conjunction with speech therapy, greater recovery from aphasia
DiscussionDiscussion There are synaptic connections between the
nucleus accumbens and both amygdala (fear; emotions) and ventral hippocampus (stress; anxiety)
There are synaptic connections between the nucleus accumbens and both amygdala (fear; emotions) and ventral hippocampus (stress; anxiety)
DiscussionDiscussion Studies that show drugs of abuse limit
future experience-dependent plasticity implicate the nucleus accumbens & parietal cortex
Complex environment affects plasticity in nucleus accumbens, caudate-putamen, and hippocampus
Studies that show drugs of abuse limit future experience-dependent plasticity implicate the nucleus accumbens & parietal cortex
Complex environment affects plasticity in nucleus accumbens, caudate-putamen, and hippocampus
ConclusionsConclusions
Dendritic morphology in the hippocampus and the amygdala may also be altered by environmental enrichment and potentially modulated by drug exposure
Exposure to drugs of abuse may limit future experience dependent plasticity
Dendritic morphology in the hippocampus and the amygdala may also be altered by environmental enrichment and potentially modulated by drug exposure
Exposure to drugs of abuse may limit future experience dependent plasticity