Extinction-reconsolidation boundaries: key to persistent attenuation of fear memories

By Marie H Monfils, K. Cowansage, E. Klann, Joseph E LeDoux. Science, 2009

914 citations recorded by the source corpus.

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.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Social Psychology

View Paper: https://www.semanticscholar.org/paper/f319bb1b2d6bab6345b709ab45144432a198c6fe

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Citations in the corpus

Flexible Kernel Memory (2010, neutral): “Part of the recent growing interest in the reconsolidation process is the hope that controlling it may assist in psychiatric disorders such as PTSD [50] or in permanent extinction of fears [51].”
Reconsolidation-Extinction Interactions in Fear Memory Attenuation: The Role of Inter-Trial Interval Variability (2017, background): “Recent studies have indeed shown that post-retrieval extinction engages mechanisms that are distinct from ‘‘standard’’ extinction (Monfils et al., 2009; Clem and Huganir, 2010; Rao-Ruiz et al., 2011; Tedesco et al., 2014; Lee et al., 2016).”
Memory engrams: Recalling the past and imagining the future (2020, background): “Conversely, activation of a remote DG contextual fear engram (labeled 25 days after contextual fear conditioning) itself may also be important for subsequent fear memory extinction (52), perhaps similar to a process referred to as reconsolidationupdating (193, 194).”
The restless engram: consolidations never end. (2012, methodology): “Schiller et al. (2010) adapted for humans the procedure devised by Monfils et al. (2009) for the rat.”
Intrusive Images in Psychological Disorders (2010, background): “Reactivation of the initial memory, by a single presentation of the stimulus, renders its association to fearful responses vulnerable to disruption by pharmacological (Kindt et al., 2009; Nader, Schafe, & LeDoux, 2000) or behavioral (Monfils et al., 2009) intervention.”
Fear Extinction as a Model for Translational Neuroscience: Ten Years of Progress (2012, background): “Extinction performed shortly after reactivation of fear memory results in a stronger extinction memory that resists return of fear manipulations, in both rats and humans (Monfils et al 2009, Schiller et al 2009).”
The molecular and systems biology of memory. (2014, positive): “To explore this idea further Monfils et al. (2009) blocked reactivated long-term fear memory in a rat by extinction training during the reconsolidation window.”