Extinction-Reconsolidation Boundaries - Key to Persistent Attenuation of Fear Memories

Background

Three well-reproduced findings in the fear conditioning literature are

1. Spontaneous recovery: increasing time between extinction and test increases responding to the conditioned stimulus (CS).
2. Reinstatement: after extinction, re-exposure to unconditioned stimulus (US) increases responding to the CS
3. Renewal: after extinction, returning animal to acquisition context increases responding to the CS

Research Questions

• Is there a pharmacologically-free method to reduce the presence of all three effects? Yes!

Experiments

Exp 1 (Behavior)

• 3 CS-US pairings
• Extinction consists of either (a) 19 extinction trials or (b) 1 extinction trial followed by 18 more extinction trials
• 5 groups: 19 back-to-back trials, 10 minutes between 1st extinction trial and 18 subsequent trials, 1hr, 6hr, 24hr
• Compare fear retrieval 24 hours later and 1 months later (spontaneous recovery) to fear retrieval at end of extinction

• In 10 minute and 1 hr groups, freezing is approximately the same
• All other groups display spontaneous recovery
• Takeaway: pre-exposing 1 extinction trial within ~1hr of extinction reduces spontaneous recovery

Exp 2 (Behavior)

• Next, test effect on renewal (place back in FC context)
• Grey is context A, Blue is context B

• Takeaway: presenting one extinction trial 1 hour before extinction blocks renewal

Exp 3 (Behavior)

• Next, test effect on reinstatement (shock before testing)
• Specifically, 5 shocks (US) without CS

• Takeaway: presenting one extinction trial 1 hour before extinction blocks reinstatement

Exp 4 (Neural)

• Molecular identification. Skipped.

Exp 5 (Behavior)

• Examine subsequent susceptibility to 2nd fear conditioning (1 CS+US)
• Then test mice over 5 CS trials

• Takeaway: Mice with 1 hour between first extinction trial and 18 subsequent extinction trials recover fear response to lesser extent

Exp 6 (Behavior)

• How quickly do mice recover fear response?
• Again, use 2nd fear conditioning (5 CS+US)

• 1 hour group acquires fear response to lesser extent than (1) group with no previous CS-US exposure (control) and (2) group with no gap between first extinction trial and 18 subsequent extinction trials