29 March 2021
Extinction-Reconsolidation Boundaries - Key to Persistent Attenuation of Fear Memories
by Monfils, ..., LeDoux (Science 2009)
Background
Three well-reproduced findings in the fear conditioning literature are
- Spontaneous recovery: increasing time between extinction and test increases responding
to the conditioned stimulus (CS).
- Reinstatement: after extinction, re-exposure to unconditioned stimulus (US) increases
responding to the CS
- 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
tags: fear-conditioning