Nader, K., Schaf, G. E. & LeDoux, J. E. Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature 406, 722-726

W.M. Keck Foundation Laboratory of Neurobiology, Center for Neural Science, New York University, New York 10003, USA.
Nature (Impact Factor: 41.46). 09/2000; 406(6797):722-6. DOI: 10.1038/35021052
Source: PubMed


'New' memories are initially labile and sensitive to disruption before being consolidated into stable long-term memories. Much evidence indicates that this consolidation involves the synthesis of new proteins in neurons. The lateral and basal nuclei of the amygdala (LBA) are believed to be a site of memory storage in fear learning. Infusion of the protein synthesis inhibitor anisomycin into the LBA shortly after training prevents consolidation of fear memories. Here we show that consolidated fear memories, when reactivated during retrieval, return to a labile state in which infusion of anisomycin shortly after memory reactivation produces amnesia on later tests, regardless of whether reactivation was performed 1 or 14 days after conditioning. The same treatment with anisomycin, in the absence of memory reactivation, left memory intact. Consistent with a time-limited role for protein synthesis production in consolidation, delay of the infusion until six hours after memory reactivation produced no amnesia. Our data show that consolidated fear memories, when reactivated, return to a labile state that requires de novo protein synthesis for reconsolidation. These findings are not predicted by traditional theories of memory consolidation.

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    • "However, already in the late 1960s Misanin et al (1968) showed that consolidated memories can be reactivated upon retrieval, brought once again to a temporary fragile state. More than three decades later, the opportunity to alter already-consolidated memories had regained interest, when Nader et al (2000) convincingly demonstrated the sensitivity of reactivated fear memories to protein synthesis inhibitors, establishing the need of protein synthesis for reconsolidation of memories after retrieval. Other studies followed, demonstrating the effects of pharmacological (eg, Kindt et al, 2009) or behavioral (Monfils et al, 2009; Schiller et al, 2010) interventions on the reconsolidation of reactivated memories. "
    Psychoneuroendocrinology 09/2015; 61:43-4. DOI:10.1016/j.psyneuen.2015.07.508 · 4.94 Impact Factor
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    • "The ability to form, store and retrieve memories is an essential requisite of normal adaptive functioning for all organisms. When memories are recalled, they enter a transient labile phase in which they can be impaired or enhanced followed by a new stabilization process termed reconsolidation (Nader et al., 2000). Reconsolidation has been demonstrated for explicit and implicit, appetitive and aversive memories in various species including humans (Dudai, 2012; Schwabe et al., 2014). "
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    ABSTRACT: When memories are recalled, they enter a transient labile phase in which they can be impaired or enhanced followed by a new stabilization process termed reconsolidation. It is unknown, however, whether reconsolidation is restricted to neurocognitive processes such as fear memories or can be extended to peripheral physiological functions as well. Here, we show in a paradigm of behaviorally conditioned taste aversion in rats reconsolidation-like processes in learned immunosuppression. The administration of sub-therapeutic doses of the immunosuppressant cyclosporin A together with the conditioned stimulus (CS/saccharin) during retrieval blocked extinction of conditioned taste aversion and learned suppression of T cell cytokine (interleukin-2; interferon-γ) production. This conditioned immunosuppression is of clinical relevance since it significantly prolonged the survival time of heterotopically transplanted heart allografts in rats. Collectively, these findings demonstrate that memories can be updated on both neural and behavioral levels as well as on the level of peripheral physiological systems such as immune functioning.
    Brain Behavior and Immunity 09/2015; DOI:10.1016/j.bbi.2015.09.009 · 5.89 Impact Factor
    • "Most broadly, protein synthesis is required for the reconsolidation of the memory (Debiec, LeDoux, & Nader, 2002; Lee, 2008; Nader et al., 2000). One of the pioneering papers in the field of reconsolidation established that reconsolidation of fear memory could be disrupted through the " post-reactivation " administration of a protein synthesis inhibitor into the amygdala of a rat (Nader et al., 2000). Since the publication of this paper, research in this field has rapidly expanded. "
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    ABSTRACT: Over the past decade, a growing body of research has sought to investigate how the pharmacological disruption of memory reconsolidation can degrade or erase memories. Much of this research has focused specifically on disrupting memories that are considered bad or maladaptive for the ultimate purpose of translation to a human population. While most of the research was pioneered in fear memory, recent studies have focused on degrading drug-cued memories in the context of addiction. Essentially, this research seeks to disrupt cues as predictors of reward or drug availability. A core component of this reconsolidation process is glutamate signaling. An overall review of the literature suggests that disruption of glutamate signaling under reconsolidation parameters is sufficient to erase drug-related memories. This review will focus on specific studies that examine the glutamatergic mechanisms of reconsolidation disruption in the context of drug addiction.
    Journal of Applied Biobehavioral Research 09/2015; 20(3). DOI:10.1111/jabr.12031
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