Cargando…
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...
Autores principales: | , , , |
---|---|
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 |
_version_ | 1783251204735762432 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5516687 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT trentsimon ampareceptorscontrolfearextinctionthroughanarcdependentmechanism AT barnesphilip ampareceptorscontrolfearextinctionthroughanarcdependentmechanism AT halljeremy ampareceptorscontrolfearextinctionthroughanarcdependentmechanism AT thomaskerriel ampareceptorscontrolfearextinctionthroughanarcdependentmechanism |