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

Reversing Pavlov Memories of fearful associations, such as hearing a tone before receiving a low-voltage shock, are labile when they are retrieved, such that the association can be extinguished or reconsolidated. Monfils et al. (p. 951, published online 2 April) demonstrate that applying a standard extinction treatment (sounding the tone multiple times in the absence of any shocks) within a window of time during which reconsolidation would normally occur has the effect of overwriting the original memory. Rats treated in this fashion display much lower levels of renewal (fear induced by sounding the tone once by itself), reinstatement (fear induced by giving the shock once by itself), and spontaneous recovery. Behavioral manipulations can reverse a learned fearful association in rats. Dysregulation of the fear system is at the core of many psychiatric disorders. Much progress has been made in uncovering the neural basis of fear learning through studies in which associative emotional memories are formed by pairing an initially neutral stimulus (conditioned stimulus, CS; e.g., a tone) to an unconditioned stimulus (US; e.g., a shock). Despite recent advances, the question of how to persistently weaken aversive CS-US associations, or dampen traumatic memories in pathological cases, remains a major dilemma. Two paradigms (blockade of reconsolidation and extinction) have been used in the laboratory to reduce acquired fear. Unfortunately, their clinical efficacy is limited: Reconsolidation blockade typically requires potentially toxic drugs, and extinction is not permanent. Here, we describe a behavioral design in which a fear memory in rats is destabilized and reinterpreted as safe by presenting an isolated retrieval trial before an extinction session. This procedure permanently attenuates the fear memory without the use of drugs.