Nader K, Schafe GE, Le Doux JE. 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: 42.35). 09/2000; 406(6797):722-6. DOI: 10.1038/35021052
Source: PubMed

ABSTRACT '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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    • "Anisomycin is a multifunctional antibiotic isolated from two different species of Streptomyces [1]. It is also an inhibitor of protein synthesis [2] [3] [4] [5] and affects memory by inhibiting the consolidation of new memories and causing amnesia [6] [7] [8] [9] [10] [11] [12] [13] [14]. Anisomycin is an immunosuppressant in low doses (b 0.1 μM; M = mol l − 1 ) indicating its possible application in treatment of some autoimmune diseases and in inhibition of the transplantation rejection [4] [5]. "
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    ABSTRACT: Anisomycin is an immunosuppressant in low doses (< 0.1 μM) with possible application in treatment of some autoimmune diseases and in inhibiting transplantation rejection. Anisomycin suppresses malignant tumor cell growth and affects memory. For the first time it was the subject of the electrochemical investigations by cyclic voltammetry and square wave voltammetry on gold electrode in 0.05 M NaHCO3 using its electrochemical activity. The cyclic voltammetry experiments at different sweep rates show that electrochemical process is irreversible and diffusion controlled. Based on square wave voltammetry measurements, the calculated values of LOD and LOQ were 1 and 4 nM (in the absence of biological fluid), as well as 2 and 6 nM (in the presence of spiked urine) indicating the high sensitivity of the proposed electroanalytical method. High performance liquid chromatography–tandem mass spectrometry was a reference method for quantification of anisomycin and served for structural identification of its hydrolysis product (deacetylanisomycin).
    Electrochemistry Communications 06/2015; 58. DOI:10.1016/j.elecom.2015.05.017 · 4.85 Impact Factor
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    • "Consolidated memories were once thought to be persistent and resistant to disruption [7]. However, accumulating evidence has challenged this hypothesis by showing that recollection returns consolidated memories to a labile state [8] [9] [10] and that in order to persist these reactivated memories must undergo a protein synthesis-dependent process referred "
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    ABSTRACT: Major depressive disorder (MDD) is characterized by a dysfunctional processing of autobiographical memories. We review the following core domains of deficit: systematic biases favoring materials of negative emotional valence; diminished access and response to positive memories; a recollection of overgeneral memories in detriment of specific autobiographical memories; and the role of ruminative processes and avoidance when dealing with autobiographical memories. Furthermore, we review evidence from functional neuroimaging studies of neural circuits activated by the recollection of autobiographical memories in both healthy and depressive individuals. Disruptions in autobiographical memories predispose and portend onset and maintenance of depression. Thus, we discuss emerging therapeutics that target memory difficulties in those with depression. We review strategies for this clinical domain, including memory specificity training, method-of-loci, memory rescripting, and real-time fMRI neurofeedback training of amygdala activity in depression. We propose that the manipulation of the reconsolidation of autobiographical memories in depression might represent a novel yet largely unexplored, domain-specific, therapeutic opportunity for depression treatment.
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    • "In our experiments, light stimulation was delivered 1 day after conditioning when mice were in their home cages. Optical stimulation of two cell ensembles is likely to trigger recall of the corresponding memories, which may lead to memory reconsolidation , a process requiring protein synthesis (Nader et al., 2000). Memory reconsolidation is assumed to underlie memory updating that, by destabilizing the original memory, integrates new and existing information (Hardt et al., 2010; Lee, 2009; Nader and Hardt, 2009; Tronson and Taylor, 2007). "
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    ABSTRACT: Memory is thought to be stored in the brain as an ensemble of cells activated during learning. Although optical stimulation of a cell ensemble triggers the retrieval of the corresponding memory, it is unclear how the association of information occurs at the cell ensemble level. Using optogenetic stimulation without any sensory input in mice, we found that an artificial association between stored, non-related contextual, and fear information was generated through the synchronous activation of distinct cell ensembles corresponding to the stored information. This artificial association shared characteristics with physiologically associated memories, such as N-methyl-D-aspartate receptor activity and protein synthesis dependence. These findings suggest that the association of information is achieved through the synchronous activity of distinct cell ensembles. This mechanism may underlie memory updating by incorporating novel information into pre-existing networks to form qualitatively new memories. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Cell Reports 04/2015; 88. DOI:10.1016/j.celrep.2015.03.017 · 7.21 Impact Factor
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