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Originally published in Science Express on 2 April 2009
Science 15 May 2009:
Vol. 324. no. 5929, pp. 951 - 955
DOI: 10.1126/science.1167975
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Reports

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

Marie-H. Monfils,1,2,* Kiriana K. Cowansage,1 Eric Klann,1 Joseph E. LeDoux1,3,4,5

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.

1 Center for Neural Science, New York University, New York, NY 10003, USA.
2 Department of Psychology, University of Texas, Austin, TX 78712, USA.
3 Department of Psychology, New York University, New York, NY 10003, USA.
4 Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA.
5 Emotional Brain Institute, New York University, New York, NY 10003, USA.

* To whom correspondence should be addressed. E-mail: monfils{at}mail.utexas.edu

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