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mTOR is essential for corticosteroid effects on hippocampal AMPA receptor function and fear memory

Glucocorticoid hormones, via activation of their receptors, promote memory consolidation, but the exact underlying mechanisms remain elusive. We examined how corticosterone regulates AMPA receptors (AMPARs), which are crucial for synaptic plasticity and memory formation. Combining a live imaging flu...

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Autores principales: Xiong, Hui, Cassé, Frédéric, Zhou, Yang, Zhou, Ming, Xiong, Zhi-Qi, Joëls, Marian, Martin, Stéphane, Krugers, Harm J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749735/
https://www.ncbi.nlm.nih.gov/pubmed/26572647
http://dx.doi.org/10.1101/lm.039420.115
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author Xiong, Hui
Cassé, Frédéric
Zhou, Yang
Zhou, Ming
Xiong, Zhi-Qi
Joëls, Marian
Martin, Stéphane
Krugers, Harm J.
author_facet Xiong, Hui
Cassé, Frédéric
Zhou, Yang
Zhou, Ming
Xiong, Zhi-Qi
Joëls, Marian
Martin, Stéphane
Krugers, Harm J.
author_sort Xiong, Hui
collection PubMed
description Glucocorticoid hormones, via activation of their receptors, promote memory consolidation, but the exact underlying mechanisms remain elusive. We examined how corticosterone regulates AMPA receptors (AMPARs), which are crucial for synaptic plasticity and memory formation. Combining a live imaging fluorescent recovery after photobleaching approach with the use of the pH-sensitive GFP-AMPAR tagging revealed that corticosterone enhances the AMPAR mobile fraction and increases synaptic trapping of AMPARs in hippocampal cells. In parallel, corticosterone-enhanced AMPAR-mediated synaptic transmission. Blocking the mammalian target of rapamycin (mTOR) pathway prevented the effects of corticosterone on both AMPAR trapping—but not on the mobile fraction—and synaptic transmission. Blocking the mTOR pathway also prevented the memory enhancing effects of corticosterone in a contextual fear-conditioning paradigm. We conclude that activation of the mTOR pathway is essential for the effects of corticosterone on synaptic trapping of AMPARs and, possibly as a consequence, fearful memory formation.
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spelling pubmed-47497352016-12-01 mTOR is essential for corticosteroid effects on hippocampal AMPA receptor function and fear memory Xiong, Hui Cassé, Frédéric Zhou, Yang Zhou, Ming Xiong, Zhi-Qi Joëls, Marian Martin, Stéphane Krugers, Harm J. Learn Mem Research Glucocorticoid hormones, via activation of their receptors, promote memory consolidation, but the exact underlying mechanisms remain elusive. We examined how corticosterone regulates AMPA receptors (AMPARs), which are crucial for synaptic plasticity and memory formation. Combining a live imaging fluorescent recovery after photobleaching approach with the use of the pH-sensitive GFP-AMPAR tagging revealed that corticosterone enhances the AMPAR mobile fraction and increases synaptic trapping of AMPARs in hippocampal cells. In parallel, corticosterone-enhanced AMPAR-mediated synaptic transmission. Blocking the mammalian target of rapamycin (mTOR) pathway prevented the effects of corticosterone on both AMPAR trapping—but not on the mobile fraction—and synaptic transmission. Blocking the mTOR pathway also prevented the memory enhancing effects of corticosterone in a contextual fear-conditioning paradigm. We conclude that activation of the mTOR pathway is essential for the effects of corticosterone on synaptic trapping of AMPARs and, possibly as a consequence, fearful memory formation. Cold Spring Harbor Laboratory Press 2015-12 /pmc/articles/PMC4749735/ /pubmed/26572647 http://dx.doi.org/10.1101/lm.039420.115 Text en © 2015 Xiong 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 Research
Xiong, Hui
Cassé, Frédéric
Zhou, Yang
Zhou, Ming
Xiong, Zhi-Qi
Joëls, Marian
Martin, Stéphane
Krugers, Harm J.
mTOR is essential for corticosteroid effects on hippocampal AMPA receptor function and fear memory
title mTOR is essential for corticosteroid effects on hippocampal AMPA receptor function and fear memory
title_full mTOR is essential for corticosteroid effects on hippocampal AMPA receptor function and fear memory
title_fullStr mTOR is essential for corticosteroid effects on hippocampal AMPA receptor function and fear memory
title_full_unstemmed mTOR is essential for corticosteroid effects on hippocampal AMPA receptor function and fear memory
title_short mTOR is essential for corticosteroid effects on hippocampal AMPA receptor function and fear memory
title_sort mtor is essential for corticosteroid effects on hippocampal ampa receptor function and fear memory
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749735/
https://www.ncbi.nlm.nih.gov/pubmed/26572647
http://dx.doi.org/10.1101/lm.039420.115
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