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The role of memory reactivation during wakefulness and sleep in determining which memories endure.
J. Neurosci.
PUBLISHED: 04-12-2013
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Consolidation makes it possible for memories of our daily experiences to be stored in an enduring way. We propose that memory consolidation depends on the covert reactivation of previously learned material both during sleep and wakefulness. Here we tested whether the operation of covert memory reactivation influences the fundamental selectivity of memory storage--of all the events we experience each day, which will be retained and which forgotten? We systematically manipulated the value of information learned by 60 young subjects; they learned 72 object-location associations while hearing characteristic object sounds, and a number on each object indicated the reward value that could potentially be earned during a future memory test. Recall accuracy declined to a greater extent for low-value than for high-value associations after either a 90 min nap or a 90 min wake interval. Yet, via targeted memory reactivation of half of the low-value associations using the corresponding sounds, these memories were rescued from forgetting. Only cued associations were rescued when sounds were applied during wakefulness, whereas the entire set of low-value associations was rescued from forgetting when the manipulation occurred during sleep. The benefits accrued from presenting corresponding sounds show that covert reactivation is a major factor determining the selectivity of memory consolidation in these circumstances. By extension, covert reactivation may determine the ultimate fate of our memories, though wake and sleep reactivation might play distinct roles in this process, the former helping to strengthen individual, salient memories, and the latter strengthening, while also linking, categorically related memories together.
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Extinction Training During the Reconsolidation Window Prevents Recovery of Fear
Authors: Daniela Schiller, Candace M. Raio, Elizabeth A. Phelps.
Published: 08-24-2012
ABSTRACT

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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