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      Calcium/calmodulin‐dependent kinase II and memory destabilization: a new role in memory maintenance

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          Abstract

          In this review, we discuss the poorly explored role of calcium/calmodulin‐dependent protein kinase II (Ca MKII) in memory maintenance, and its influence on memory destabilization. After a brief review on Ca MKII and memory destabilization, we present critical pieces of evidence suggesting that Ca MKII activity increases retrieval‐induced memory destabilization. We then proceed to propose two potential molecular pathways to explain the association between Ca MKII activation and increased memory destabilization. This review will pinpoint gaps in our knowledge and discuss some ‘controversial’ observations, establishing the basis for new experiments on the role of Ca MKII in memory reconsolidation. The role of Ca MKII in memory destabilization is of great clinical relevance. Still, because of the lack of scientific literature on the subject, more basic science research is necessary to pursue this pathway as a clinical tool.

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          Most cited references109

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          Neural mechanisms of extinction learning and retrieval.

          Emotional learning is necessary for individuals to survive and prosper. Once acquired, however, emotional associations are not always expressed. Indeed, the regulation of emotional expression under varying environmental conditions is essential for mental health. The simplest form of emotional regulation is extinction, in which conditioned responding to a stimulus decreases when the reinforcer is omitted. Two decades of research on the neural mechanisms of fear conditioning have laid the groundwork for understanding extinction. In this review, we summarize recent work on the neural mechanisms of extinction learning. Like other forms of learning, extinction occurs in three phases: acquisition, consolidation, and retrieval, each of which depends on specific structures (amygdala, prefrontal cortex, hippocampus) and molecular mechanisms (receptors and signaling pathways). Pharmacological methods to facilitate consolidation and retrieval of extinction, for both aversive and appetitive conditioning, are setting the stage for novel treatments for anxiety disorders and addictions.
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            The molecular basis of CaMKII function in synaptic and behavioural memory.

            Long-term potentiation (LTP) in the CA1 region of the hippocampus has been the primary model by which to study the cellular and molecular basis of memory. Calcium/calmodulin-dependent protein kinase II (CaMKII) is necessary for LTP induction, is persistently activated by stimuli that elicit LTP, and can, by itself, enhance the efficacy of synaptic transmission. The analysis of CaMKII autophosphorylation and dephosphorylation indicates that this kinase could serve as a molecular switch that is capable of long-term memory storage. Consistent with such a role, mutations that prevent persistent activation of CaMKII block LTP, experience-dependent plasticity and behavioural memory. These results make CaMKII a leading candidate in the search for the molecular basis of memory.
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              Memory Engram Cells Have Come of Age.

              The idea that memory is stored in the brain as physical alterations goes back at least as far as Plato, but further conceptualization of this idea had to wait until the 20(th) century when two guiding theories were presented: the "engram theory" of Richard Semon and Donald Hebb's "synaptic plasticity theory." While a large number of studies have been conducted since, each supporting some aspect of each of these theories, until recently integrative evidence for the existence of engram cells and circuits as defined by the theories was lacking. In the past few years, the combination of transgenics, optogenetics, and other technologies has allowed neuroscientists to begin identifying memory engram cells by detecting specific populations of cells activated during specific learning epochs and by engineering them not only to evoke recall of the original memory, but also to alter the content of the memory.
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                Author and article information

                Contributors
                karl.giese@kcl.ac.uk
                Journal
                J Neurochem
                J. Neurochem
                10.1111/(ISSN)1471-4159
                JNC
                Journal of Neurochemistry
                John Wiley and Sons Inc. (Hoboken )
                0022-3042
                1471-4159
                27 June 2018
                October 2018
                : 147
                : 1 ( doiID: 10.1111/jnc.2018.147.issue-1 )
                : 12-23
                Affiliations
                [ 1 ] Department of Cell and Integrative Physiology The University of Texas Health San Antonio 8403, Floyd Curl Drive San Antonio TX 78229 USA
                [ 2 ] Department of Basic and Clinical Neuroscience King's College London 125 Coldharbour Lane London SE5 9NU UK
                Author notes
                [*] [* ]Address correspondence and reprint requests to Prof. K. Peter Giese, Department of Basic and Clinical Neuroscience, King's College London, Institute of Psychiatry, Psychology and Neuroscience, 125 Coldharbour Lane, London SE5 9NU, UK. E‐mail: karl.giese@ 123456kcl.ac.uk .
                Author information
                http://orcid.org/0000-0003-4503-7344
                Article
                JNC14454
                10.1111/jnc.14454
                6221169
                29704430
                fca27cad-57df-4b0d-a576-a685c16b4fa4
                © 2018 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 08 February 2018
                : 28 March 2018
                : 17 April 2018
                Page count
                Figures: 3, Tables: 1, Pages: 12, Words: 10281
                Funding
                Funded by: Brazilian National Council for Scientific and Technological Development (CNPq)
                Funded by: Medical Research Council
                Categories
                Review
                Review Article
                Custom metadata
                2.0
                jnc14454
                October 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.5.1 mode:remove_FC converted:07.11.2018

                Neurosciences
                calcium/calmodulin‐dependent kinase ii,reconsolidation,synaptic signaling
                Neurosciences
                calcium/calmodulin‐dependent kinase ii, reconsolidation, synaptic signaling

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