'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.
"Whereas propranolol was first studied as a general anxiolytic in the treatment of anxiety disorders, today it is mainly the amnesic effect on retrieved fear memory that is the subject of interest. To this end, there is evidence to suggest that after a fear memory is recollected, and followed specifically by a prediction error (a discrepancy between actual and expected negative events), propranolol selectively blocks protein synthesis, thereby prohibiting the 'reconsolidation' of the fear memory while sparing declarative memory (Debiec and Ledoux, 2004; Finnie and Nader, 2012; Kindt et al., 2009; Merlo et al., 2014, 2015; Nader et al., 2000; Sevenster et al., 2013). A recent metaanalysis of eight experiments with healthy human volunteers (total n = 308) supported this line of reasoning as it was found that compared with placebo, propranolol administered before memory reactivation is capable of reducing the expression of cue-elicited fear responses (Lonergan et al., 2013). "
[Show abstract][Hide abstract] ABSTRACT: The effects of propranolol in the treatment of anxiety disorders have not been systematically evaluated previously. The aim was to conduct a systematic review and meta-analysis of randomised controlled trials, addressing the efficacy of oral propranolol versus placebo or other medication as a treatment for alleviating either state or trait anxiety in patients suffering from anxiety disorders. Eight studies met the inclusion criteria. These studies concerned panic disorder with or without agoraphobia (four studies, total n = 130), specific phobia (two studies, total n = 37), social phobia (one study, n = 16), and posttraumatic stress disorder (PTSD) (one study, n = 19). Three out of four panic disorder trials qualified for pooled analyses. These meta-analyses found no statistically significant differences between the efficacy of propranolol and benzodiazepines regarding the short-term treatment of panic disorder with or without agoraphobia. Also, no evidence was found for effects of propranolol on PTSD symptom severity through inhibition of memory reconsolidation. In conclusion, the quality of evidence for the efficacy of propranolol at present is insufficient to support the routine use of propranolol in the treatment of any of the anxiety disorders.
Journal of Psychopharmacology 10/2015; DOI:10.1177/0269881115612236 · 3.59 Impact Factor
"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. "
"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). "
[Show abstract][Hide abstract] 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
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