We thank D. Johnson and K. Doelling for assistance with data collection. We also thank M.-H. Monfils, J. LeDoux, Y. Niv and M. Milad for advice on the experimental protocols. This study was funded by the James S. McDonnell Foundation and National Institutes of Health (NIH) grant R21 MH072279 (E.A.P.), NIH grants R37 MH038774, P50 MH058911, RO1 MH046516 and K05 MH067048 (J.E.L.), Postdoctoral fellowships NSERC, CIHR and AHFMR (M.-H.M.), and a Fulbright and Blavatnik awards (D.S.).

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No conflicts of interest declared.

The protocol we presented here enables creating a simple conditioned fear response to a neutral stimulus paired with an aversive outcome. A day later we reactivated the fear memory in order to trigger its reconsolidation. During this stage we induced interference in the form of extinction training. To verify that extinction affects reconsolidation we used two control groups. One group underwent extinction without the reminder trial triggering reconsolidation, and another group experienced the reminder trial but then unde...

extinction training during the reconsolidation window prevents recovery of fear

Fear is maladaptive when it persists long after circumstances have become safe. It is therefore crucial to develop an approach that persistently prevents the return of fear. Pavlovian fear-conditioning paradigms are commonly employed to create a controlled, novel fear association in the laboratory. After pairing an innocuous stimulus (conditioned stimulus, CS) with an aversive outcome (unconditioned stimulus, US) we can elicit a fear response (conditioned response, or CR) by presenting just the stimulus alone1,2 . Once fear is acquired, it can be diminished using extinction training, whereby the conditioned stimulus is repeatedly presented without the aversive outcome until fear is no longer expressed3. This inhibitory learning creates a new, safe representation for the CS, which competes for expression with the original fear memory4. Although extinction is effective at inhibiting fear, it is not permanent. Fear can spontaneously recover with the passage of time. Exposure to stress or returning to the context of initial learning can also cause fear to resurface3,4.
Our protocol addresses the transient nature of extinction by targeting the reconsolidation window to modify emotional memory in a more permanent manner. Ample evidence suggests that reactivating a consolidated memory returns it to a labile state, during which the memory is again susceptible to interference5-9. This window of opportunity appears to open shortly after reactivation and close approximately 6hrs later5,11,16, although this may vary depending on the strength and age of the memory15. By allowing new information to incorporate into the original memory trace, this memory may be updated as it reconsolidates10,11. Studies involving non-human animals have successfully blocked the expression of fear memory by introducing pharmacological manipulations within the reconsolidation window, however, most agents used are either toxic to humans or show equivocal effects when used in human studies12-14. Our protocol addresses these challenges by offering an effective, yet non-invasive, behavioral manipulation that is safe for humans.
By prompting fear memory retrieval prior to extinction, we essentially trigger the reconsolidation process, allowing new safety information (i.e., extinction) to be incorporated while the fear memory is still susceptible to interference. A recent study employing this behavioral manipulation in rats has successfully blocked fear memory using these temporal parameters11. Additional studies in humans have demonstrated that introducing new information after the retrieval of previously consolidated motor16, episodic17, or declarative18 memories leads to interference with the original memory trace14. We outline below a novel protocol used to block fear recovery in humans.

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Extinction Training During the Reconsolidation Window Prevents Recovery of Fear

Conditioned fear can be diminished through an inhibitory process called extinction, but can resurface under conditions such as the passage of time or exposure to stress. Our protocol presents a novel way of preventing fear recovery by introducing extinction during the reconsolidation window (the re-storage phase of a reactivated memory).

Fear is maladaptive when it persists long after circumstances have become safe. It is therefore crucial to develop an approach that persistently prevents ...

extinction-training-during-reconsolidation-window-prevents-recovery

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24.9K Views.  Mt. Sinai School of Medicine. Conditioned fear can be diminished through an inhibitory process called extinction, but can resurface under conditions such as the passage of time or exposure to stress. Our protocol presents a novel way of preventing fear recovery by introducing extinction during the reconsolidation window (the re-storage phase of a reactivated memory).