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AMPA receptors control fear extinction through an Arc-dependent mechanism

Activity-regulated cytoskeleton-associated protein (Arc) supports fear memory through synaptic plasticity events requiring actin cytoskeleton rearrangements. We have previously shown that reducing hippocampal Arc levels through antisense knockdown leads to the premature extinction of contextual fear...

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Detalles Bibliográficos
Autores principales: Trent, Simon, Barnes, Philip, Hall, Jeremy, Thomas, Kerrie L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516687/
https://www.ncbi.nlm.nih.gov/pubmed/28716957
http://dx.doi.org/10.1101/lm.045013.117
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author Trent, Simon
Barnes, Philip
Hall, Jeremy
Thomas, Kerrie L.
author_facet Trent, Simon
Barnes, Philip
Hall, Jeremy
Thomas, Kerrie L.
author_sort Trent, Simon
collection PubMed
description Activity-regulated cytoskeleton-associated protein (Arc) supports fear memory through synaptic plasticity events requiring actin cytoskeleton rearrangements. We have previously shown that reducing hippocampal Arc levels through antisense knockdown leads to the premature extinction of contextual fear. Here we show that the AMPA receptor antagonist CNQX elevates hippocampal Arc levels during extinction and blocks extinction that can be rescued by reducing Arc. Increasing Arc levels with CNQX also overcomes the actin-destabilizing properties of cytochalasin D and promotes extinction. Therefore, extinction is dependent on AMPA-mediated reductions of Arc via a mechanism consistent with a role for Arc in stabilizing the actin cytoskeleton to constrain extinction.
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spelling pubmed-55166872018-08-01 AMPA receptors control fear extinction through an Arc-dependent mechanism Trent, Simon Barnes, Philip Hall, Jeremy Thomas, Kerrie L. Learn Mem Brief Communication Activity-regulated cytoskeleton-associated protein (Arc) supports fear memory through synaptic plasticity events requiring actin cytoskeleton rearrangements. We have previously shown that reducing hippocampal Arc levels through antisense knockdown leads to the premature extinction of contextual fear. Here we show that the AMPA receptor antagonist CNQX elevates hippocampal Arc levels during extinction and blocks extinction that can be rescued by reducing Arc. Increasing Arc levels with CNQX also overcomes the actin-destabilizing properties of cytochalasin D and promotes extinction. Therefore, extinction is dependent on AMPA-mediated reductions of Arc via a mechanism consistent with a role for Arc in stabilizing the actin cytoskeleton to constrain extinction. Cold Spring Harbor Laboratory Press 2017-08 /pmc/articles/PMC5516687/ /pubmed/28716957 http://dx.doi.org/10.1101/lm.045013.117 Text en © 2017 Trent et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first 12 months after the full-issue publication date (see http://learnmem.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Brief Communication
Trent, Simon
Barnes, Philip
Hall, Jeremy
Thomas, Kerrie L.
AMPA receptors control fear extinction through an Arc-dependent mechanism
title AMPA receptors control fear extinction through an Arc-dependent mechanism
title_full AMPA receptors control fear extinction through an Arc-dependent mechanism
title_fullStr AMPA receptors control fear extinction through an Arc-dependent mechanism
title_full_unstemmed AMPA receptors control fear extinction through an Arc-dependent mechanism
title_short AMPA receptors control fear extinction through an Arc-dependent mechanism
title_sort ampa receptors control fear extinction through an arc-dependent mechanism
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516687/
https://www.ncbi.nlm.nih.gov/pubmed/28716957
http://dx.doi.org/10.1101/lm.045013.117
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