| Abstract: |
Many common psychiatric
conditions involve problems related to fear (e.g., phobias, panic, and post-traumatic
stress disorder). Our understanding of fear processing comes largely from
studies of Pavlovian conditioning, a behavioral paradigm in which an initially
neutral stimulus (conditioned stimulus, CS; e.g., a tone) acquires the ability
to elicit a conditioned response (CR; e.g., freezing) after its pairing
with an unconditioned stimulus (US; e.g., a shock). When new information
is acquired, the memory is initially unstable, but then consolidates into
long-term storage through protein synthesis. Previously consolidated memories
actually revert to a mutable state when subsequently retrieved, and that
a second cycle of protein synthesis is then required to restore the stable
condition of memories: a process termed reconsolidation. Pharmacologically
interfering with mechanisms triggered during fear retrieval enables the
targeted modification of memories in the lateral nucleus of the amygdala
(LA). Here we describe, in rats, a novel protocol in which we modified consolidated
fear memories using behavioral training. We show that a single isolated
retrieval trial given prior to a session in which the CS was repeatedly
presented (extinction) progressively attenuates freezing, blocks reconsolidation,
and prevents return of fear as evidenced by a lack of reinstatement, renewal,
or spontaneous recovery. This work may provide a new approach for treating
traumatic memory without the use of drugs. |