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

• 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

• Corticosterone response during a stressor is necessary to initiate a long process that mediates enhanced conditioning

• Experiment 1:– Determine whether BNST is critically involved

in enhanced conditioning

• Experiment 2: – Determine when BNST is involved

• During stressor

• During training

Experiment 1

• Male Sprague-Dawley rats– 60-90 days old

– Housed singly

– Food and water ad lib

– 12 hr. light dark cycle

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

• 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

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

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

Experiment 1

• Total rats: 27 – 6 unstressed sham– 7 stressed sham– 7 unstressed lesioned– 7 stressed lesioned

Experiment 2

• Cannulae implanted to temporarily inactivate the BNST with Muscimol – GABAA receptor agonist

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

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

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

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

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

Experiment 1

• No group differences until 300 trials

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

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

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

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

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

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

Experiment 2

• Another subset reexposed to stressor 5 days later and blood collected

• BNST inactivation not prevent corticosterone response to stressor

Experiment 2

• BNST inactivation during stressor continue to release corticosterone and not different from stressed with vehicle infusion

Therefore, Professor Predator Says

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

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

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

Discussion

• Additional structures:– Hippocampus– Cerebellum

• Both highly connected with BNST and both necessary for trace conditioning

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

Cerebellum Pathway

Discussion

• BNST is also critically involved in other stress effects on learning– Lesions prevent the “learned helplessness”

effect

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

The End