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The Bed Nucleus of the Stria Terminalis Is Critically Involved in Enhancing Associative
Learning After Stressfull Experience
By Debra Bangasser, Jessica Santollo and Tracey Shors
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• Stressful events influence new memories– Exposure to acute stress facilitates classical
eyeblink conditioning
• Stressors increase the release of corticosterone – Adrenalectomy prevents facilitation of eyeblink
conditioning– Effect still seen 24 hrs after stressor event
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• Corticosterone response during a stressor is necessary to initiate a long process that mediates enhanced conditioning
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• Experiment 1:– Determine whether BNST is critically involved
in enhanced conditioning
• Experiment 2: – Determine when BNST is involved
• During stressor
• During training
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Experiment 1
• Male Sprague-Dawley rats– 60-90 days old
– Housed singly
– Food and water ad lib
– 12 hr. light dark cycle
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Experiment 1
• Cannula implanted into BNST to lesion or sham lesion
• 2 pairs of electrodes implanted through upper eyelid and attached to head stage– 1 electrode in the muscle– 1 electrode outside of the muscle
• CS = 83-dB white noise• US = 0.40-mA eyelid shock
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• Eyeblinks defined as a change in electromyographic activity
• Stressor:– restraint tube in a dark sound attenuating
chamber with 30 tail shocks at 1 per minute– 24 h before training
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Experiment 1
• Eyeblink conditioning:– Establish baseline for 30 500 msec. trials– 10: 250 msec CS only and blinks recorded for
½ sec. Afterward
• Trace conditioning: 200 trials for 2 days– CS separated by periorbital US by 500 msec
interval– Volume and intensity chosen to produce a slow
rate of acquisition
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Experiment 1
• Trials occurred in sets of 10:– 1: CS alone – 4: paired trials– 1: US alone– 4: paired trials
• Conditioned Responses (CR) = – Eyeblinks occurring 500 msec after paired trials– Eyeblinks occurring 750 msec after CS
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Experiment 1
• Total rats: 27 – 6 unstressed sham– 7 stressed sham– 7 unstressed lesioned– 7 stressed lesioned
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Experiment 2
• Cannulae implanted to temporarily inactivate the BNST with Muscimol – GABAA receptor agonist
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Experiment 2
• Trained at 100 trials per day– Group 1= inactivation before stressor and
vehicle before each training– Group 2 = vehicle before stressor and
inactivation before training– Group 3 = vehicle before stressor and training– Group 4 = no stress, but muscimol on the day
would have stress and vehicle before each training
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Experiment 2
– Verify inactivation did not inhibit eyeblink conditioning, whether affected acquisition of CR
• Low responders chosen and given 100 additional trials with BNST inactivated
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Experiment 2
• Examining:– Effects of muscimol in BNST in those who
already learned task• Exposed to 100 additional trials
• If inactivation disrupts performance, the CR would decrease
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Results
• Experiment 1– Assess whether BNST lesions prevent stress-
induced facilitation of eyeblink conditioning.• Before training there was no effect on baseline
eyeblinks with BNST lesion
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Results – Experiment 1
• Stressed with sham surgeries higher percentage of CRs than unstressed with sham
• Stressed with lesion to BNST had smaller percentage of CRs than stressed with sham– Not different from unstressed with sham
• Unstressed with lesions had fewer CRs than stressed after a sham surgery
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Experiment 1
• No group differences until 300 trials
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Experiment 1
• Sham surgery + stressor = more CR
• With BNST lesion and stressor similar to unstressed
• BNST neuronal activity necessary to facilitate trace conditioning after stress
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Results - Experiment 2
• Whether BNST is involved during the stressor or 24 h later during training.– BNST inactivation did not alter baseline blink
rate or response to CS before training– No group differences until 200 trials
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Experiment 2
• Stressed rats infused with vehicle had more CR than unstressed, but not significant
• Exposed to stressor and injected with vehicle = more CR
• BNST inactivation during stressor = more CR
• BNST inactivation during training = no increase
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Experiment 2
• Suggests BNST necessary for enhanced conditioning after stress
• BNST inactivation prevented enhancement of eyeblink conditioning after stress but only when inactivation during training
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Experiment 2
• BNST inactivation during training with high intensity US rapidly acquire CR and similar to unstressed without inactivation
• Both groups acquire more rapidly with higher intensity
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Experiment 2
• BNST inactivation does not prevent expression of CR, but low responses could be from muscimol preventing the acquistion of eyeblink conditioning
• In the presence of muscimol allowed acquisiton of CR at higher US intensity and perform similarly to unstressed controls
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Experiment 2
• Another subset reexposed to stressor 5 days later and blood collected
• BNST inactivation not prevent corticosterone response to stressor
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Experiment 2
• BNST inactivation during stressor continue to release corticosterone and not different from stressed with vehicle infusion
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Therefore, Professor Predator Says
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Discussion
• BNST critically mediates enhanced conditioning
• BNST inactivation during stressor did not prevent stress-induced enhancement of conditioning, but BNST inactivation during training did prevent stress enhancement
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Discussion
• BNST involved in stress-induced modulation of learning, but not learning itself
• Critically mediates persistent enhancement of conditioning after exposure to acute stress
• BNST does not prevent corticosterone response
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Discussion
• Amygdala involved in enhanced conditioning after stressful experience
• BNST not involved during stressor, but necessary during training
• Critical but both involved at different time points
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Discussion
• Additional structures:– Hippocampus– Cerebellum
• Both highly connected with BNST and both necessary for trace conditioning
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Discussion
• Cerebellum– Connected to BNST by direct projections to
Pons to relay sensory information about CS to cerebellum
• Stress exposure may alter the way CS is processed during training through connections of BNST to pontine nuclei
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Cerebellum Pathway
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Discussion
• BNST is also critically involved in other stress effects on learning– Lesions prevent the “learned helplessness”
effect
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Discussion
• Theorized the BNST mediates stress effects through anxiety– Exposure to acute stress induces long-lasting
state of anxiety
• The state of anxiety may enhance an animal’s ability to form basic associative memories
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The End