Does Reconsolidation Occur in Humans?

Schiller, Daniela; Phelps, Elizabeth A.

doi:10.3389/fnbeh.2011.00024

Cited by 190 publications

(203 citation statements)

References 120 publications

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confidence: 79%

“…Behavioral interference of reconsolidation using extinction has been linked to alterations in glutamate receptor function in the amygdala, which plays a critical role in memory plasticity (10,12). These findings are consistent with the suggestion that, in contrast to standard extinction training, extinction during reconsolidation may lead to long-lasting changes in the original threat memory (13,16,23).To date, the impact of extinction occurring during threat memory reconsolidation on PFC involvement is unknown in humans and other species. Animal studies of standard extinction training (i.e., repeated presentations of a conditioned stimulus without the aversive outcome) show that extinction learning and recall are mediated via the infralimbic (IL) region of the medial PFC and its connections with the amygdala; IL projections activate inhibitory cells within the amygdala that block the generation of the defense response (24,25).…”

supporting

confidence: 77%

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Extinction during reconsolidation of threat memory diminishes prefrontal cortex involvement

Schiller

Kanen²,

LeDoux

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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260

254

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Controlling learned defensive responses through extinction does not alter the threat memory itself, but rather regulates its expression via inhibitory influence of the prefrontal cortex (PFC) over amygdala. Individual differences in amygdala-PFC circuitry function have been linked to trait anxiety and posttraumatic stress disorder. This finding suggests that exposure-based techniques may actually be least effective in those who suffer from anxiety disorders. A theoretical advantage of techniques influencing reconsolidation of threat memories is that the threat representation is altered, potentially diminishing reliance on this PFC circuitry, resulting in a more persistent reduction of defensive reactions. We hypothesized that timing extinction to coincide with threat memory reconsolidation would prevent the return of defensive reactions and diminish PFC involvement. Two conditioned stimuli (CS) were paired with shock and the third was not. A day later, one stimulus (reminded CS+) but not the other (nonreminded CS+) was presented 10 min before extinction to reactivate the threat memory, followed by extinction training for all CSs. The recovery of the threat memory was tested 24 h later. Extinction of the nonreminded CS+ (i.e., standard extinction) engaged the PFC, as previously shown, but extinction of the reminded CS+ (i.e., extinction during reconsolidation) did not. Moreover, only the nonreminded CS+ memory recovered on day 3. These results suggest that extinction during reconsolidation prevents the return of defensive reactions and diminishes PFC involvement. Reducing the necessity of the PFC-amygdala circuitry to control defensive reactions may help overcome a primary obstacle in the long-term efficacy of current treatments for anxiety disorders.fear | Pavlovian conditioning | defense | learning E fforts to control maladaptive defensive reactions through extinction or exposure therapy are sometimes short-lived because these techniques do not significantly alter the threat memory itself, but rather regulate its expression via the prefrontal cortex's (PFC) inhibition of the amygdala (1, 2). Individual variation in the integrity of this amygdala-prefrontal circuitry has been linked to trait anxiety and posttraumatic stress disorder, suggesting that exposure-based techniques may be least effective in those who suffer from anxiety disorders (3-9).Recently, it has been shown in mice (10, 11), rats (12), and humans (13-16) that precisely timing behavioral extinction to coincide with memory reconsolidation can persistently inhibit the return of defensive reactions (but see refs. 17-19 for a discussion of boundary conditions). Reconsolidation is the state to which memories enter upon retrieval, which makes them prone to interference (20)(21)(22). Behavioral interference of reconsolidation using extinction has been linked to alterations in glutamate receptor function in the amygdala, which plays a critical role in memory plasticity (10,12). These findings are consistent with the suggestion that, in contrast to standar...

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supporting

confidence: 79%

supporting

confidence: 77%

Extinction during reconsolidation of threat memory diminishes prefrontal cortex involvement

Schiller

Kanen²,

LeDoux

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

260

254

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“…For example, b-adrenergic antagonists, such as propranolol, have few side effects and were reported to block reconsolidation of aversive and appetitive memories preferentially stored in the amygdala. However, behaviorally updating or extinguishing the reactivated memory during the time window of reconsolidation in the absence of drug treatment, or the use of sensory distractors, may also be used to block reconsolidation in potential treatment protocols in humans (Schiller et al 2010;Schiller and Phelps 2011;Gray and Liotta 2012).…”

Section: Potential Clinical Implicationsmentioning

confidence: 99%

Reconsolidation and the Dynamic Nature of Memory

Nader

2015

Cold Spring Harb Perspect Biol

147

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Memory reconsolidation is the process in which reactivated long-term memory (LTM) becomes transiently sensitive to amnesic agents that are effective at consolidation. The phenomenon was first described more than 50 years ago but did not fit the dominant paradigm that posited that consolidation takes place only once per LTM item. Research on reconsolidation was revitalized only more than a decade ago with the demonstration of reconsolidation in a well-defined behavioral protocol (auditory fear conditioning in the rat) subserved by an identified brain circuit (basolateral amygdala). Since then, reconsolidation has been shown in many studies over a range of species, tasks, and amnesic agents, and cellular and molecular correlates of reconsolidation have also been identified. In this review, I will first define the evidence on which reconsolidation is based, and proceed to discuss some of the conceptual issues facing the field in determining when reconsolidation does and does not occur. Last, I will refer to the potential clinical implications of reconsolidation.

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“…Despite the proliferation of research on reconsolidation, few studies have involved human subjects, perhaps because most pharmacological consolidation blockers are unsuitable for human use (3,4). When reconsolidation associated memory impairments are demonstrated in humans, the effects have been limited to fear conditioning (5)(6)(7)(8), motor sequence learning (9), and drug-induced craving (10).…”

mentioning

confidence: 99%

Impairing existing declarative memory in humans by disrupting reconsolidation

Chan

LaPaglia²

2013

Proc. Natl. Acad. Sci. U.S.A.

121

170

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During the past decade, a large body of research has shown that memory traces can become labile upon retrieval and must be restabilized. Critically, interrupting this reconsolidation process can abolish a previously stable memory. Although a large number of studies have demonstrated this reconsolidation associated amnesia in nonhuman animals, the evidence for its occurrence in humans is far less compelling, especially with regard to declarative memory. In fact, reactivating a declarative memory often makes it more robust and less susceptible to subsequent disruptions. Here we show that existing declarative memories can be selectively impaired by using a noninvasive retrieval-relearning technique. In six experiments, we show that this reconsolidation-associated amnesia can be achieved 48 h after formation of the original memory, but only if relearning occurred soon after retrieval. Furthermore, the amnesic effect persists for at least 24 h, cannot be attributed solely to source confusion and is attainable only when relearning targets specific existing memories for impairment. These results demonstrate that human declarative memory can be selectively rewritten during reconsolidation.forgetting | human memory | misinformation effect | testing effect | eyewitness memory T he entrenched view that memory becomes permanent upon consolidation has faced considerable scrutiny based on recent works demonstrating that retrieval can destabilize existing memories, and that the reactivated memories need to be reconsolidated (1, 2). During the past decade, a growing body of evidence has revealed the chemical and molecular nature of reconsolidation and its behavioral consequences (3). Critically, when a consolidated memory (e.g., a conditioned fear response) is retrieved, it becomes labile and requires protein synthesis for restabilization, and later retrieval of that memory can be severely impaired if an amnesic treatment is administered during the reconsolidation process.Despite the proliferation of research on reconsolidation, few studies have involved human subjects, perhaps because most pharmacological consolidation blockers are unsuitable for human use (3, 4). When reconsolidation associated memory impairments are demonstrated in humans, the effects have been limited to fear conditioning (5-8), motor sequence learning (9), and drug-induced craving (10). To date, we are aware of no study that has shown reconsolidation-associated impairment in declarative memory. Indeed, even when oral administration of propranolol (a systemic pharmacological consolidation blocker approved for human use) reduced the emotional response associated with a fear-inducing experience (6, 7), it left the declarative recollection intact.* Although several studies have examined whether existing declarative memories can be impaired by interference upon reactivation, none has shown memory impairments similar to those regularly exhibited in fear conditioning. Moreover, these studies used a reminder to trigger reactivation of the original memory while pro...

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Does Reconsolidation Occur in Humans?

Cited by 190 publications

References 120 publications

Extinction during reconsolidation of threat memory diminishes prefrontal cortex involvement

Extinction during reconsolidation of threat memory diminishes prefrontal cortex involvement

Reconsolidation and the Dynamic Nature of Memory

Impairing existing declarative memory in humans by disrupting reconsolidation

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