The Bed Nucleus of the Stria Terminalis Is Critically Involved in Enhancing Associative Learning...

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