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Bridging Synaptic and Epigenetic Maintenance Mechanisms of the Engram

How memories are maintained, and how memories are lost during aging or disease, are intensely investigated issues. Arguably, the reigning theory is that synaptic modifications allow for the formation of engrams during learning, and sustaining engrams sustains memory. Activity-regulated gene expressi...

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Detalles Bibliográficos
Autores principales: Kyrke-Smith, Madeleine, Williams, Joanna M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182070/
https://www.ncbi.nlm.nih.gov/pubmed/30344478
http://dx.doi.org/10.3389/fnmol.2018.00369
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author Kyrke-Smith, Madeleine
Williams, Joanna M.
author_facet Kyrke-Smith, Madeleine
Williams, Joanna M.
author_sort Kyrke-Smith, Madeleine
collection PubMed
description How memories are maintained, and how memories are lost during aging or disease, are intensely investigated issues. Arguably, the reigning theory is that synaptic modifications allow for the formation of engrams during learning, and sustaining engrams sustains memory. Activity-regulated gene expression profiles have been shown to be critical to these processes, and their control by the epigenome has begun to be investigated in earnest. Here, we propose a novel theory as to how engrams are sustained. We propose that many of the genes that are currently believed to underlie long-term memory are actually part of a “plasticity transcriptome” that underpins structural and functional modifications to neuronal connectivity during the hours to days following learning. Further, we hypothesize that a “maintenance transcriptome” is subsequently induced that includes epigenetic negative regulators of gene expression, particularly histone deacetylases. The maintenance transcriptome negatively regulates the plasticity transcriptome, and thus the plastic capability of a neuron, after learning. In this way, the maintenance transcriptome would act as a metaplasticity mechanism that raises the threshold for change in neurons within an engram, helping to ensure the connectivity is stabilized and memory is maintained.
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spelling pubmed-61820702018-10-19 Bridging Synaptic and Epigenetic Maintenance Mechanisms of the Engram Kyrke-Smith, Madeleine Williams, Joanna M. Front Mol Neurosci Neuroscience How memories are maintained, and how memories are lost during aging or disease, are intensely investigated issues. Arguably, the reigning theory is that synaptic modifications allow for the formation of engrams during learning, and sustaining engrams sustains memory. Activity-regulated gene expression profiles have been shown to be critical to these processes, and their control by the epigenome has begun to be investigated in earnest. Here, we propose a novel theory as to how engrams are sustained. We propose that many of the genes that are currently believed to underlie long-term memory are actually part of a “plasticity transcriptome” that underpins structural and functional modifications to neuronal connectivity during the hours to days following learning. Further, we hypothesize that a “maintenance transcriptome” is subsequently induced that includes epigenetic negative regulators of gene expression, particularly histone deacetylases. The maintenance transcriptome negatively regulates the plasticity transcriptome, and thus the plastic capability of a neuron, after learning. In this way, the maintenance transcriptome would act as a metaplasticity mechanism that raises the threshold for change in neurons within an engram, helping to ensure the connectivity is stabilized and memory is maintained. Frontiers Media S.A. 2018-10-05 /pmc/articles/PMC6182070/ /pubmed/30344478 http://dx.doi.org/10.3389/fnmol.2018.00369 Text en Copyright © 2018 Kyrke-Smith and Williams. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Kyrke-Smith, Madeleine
Williams, Joanna M.
Bridging Synaptic and Epigenetic Maintenance Mechanisms of the Engram
title Bridging Synaptic and Epigenetic Maintenance Mechanisms of the Engram
title_full Bridging Synaptic and Epigenetic Maintenance Mechanisms of the Engram
title_fullStr Bridging Synaptic and Epigenetic Maintenance Mechanisms of the Engram
title_full_unstemmed Bridging Synaptic and Epigenetic Maintenance Mechanisms of the Engram
title_short Bridging Synaptic and Epigenetic Maintenance Mechanisms of the Engram
title_sort bridging synaptic and epigenetic maintenance mechanisms of the engram
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182070/
https://www.ncbi.nlm.nih.gov/pubmed/30344478
http://dx.doi.org/10.3389/fnmol.2018.00369
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