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Stress induces insertion of calcium-permeable AMPA receptors in the OFC–BLA synapse and modulates emotional behaviours in mice
Stress increases the risk of neuropsychiatric disorders, such as major depression. Exposure to stress has been reported to induce various neuronal changes, such as alterations in synaptic transmission and structure. However, a causal link between stress-induced neural circuit alterations and changes...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235080/ https://www.ncbi.nlm.nih.gov/pubmed/32424318 http://dx.doi.org/10.1038/s41398-020-0837-3 |
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author | Kuniishi, Hiroshi Yamada, Daisuke Wada, Keiji Yamada, Mitsuhiko Sekiguchi, Masayuki |
author_facet | Kuniishi, Hiroshi Yamada, Daisuke Wada, Keiji Yamada, Mitsuhiko Sekiguchi, Masayuki |
author_sort | Kuniishi, Hiroshi |
collection | PubMed |
description | Stress increases the risk of neuropsychiatric disorders, such as major depression. Exposure to stress has been reported to induce various neuronal changes, such as alterations in synaptic transmission and structure. However, a causal link between stress-induced neural circuit alterations and changes in emotional behaviours is not well understood. In the present study, we focused on a projection pathway from the orbitofrontal cortex (OFC) to the basolateral nucleus of the amygdala (BLA) as a crucial circuit for negative emotions and examined the effect of stress on OFC–BLA excitatory synaptic transmission using optogenetic and whole-cell patch-clamp methods in mice. As a stress-inducing procedure, we used repeated tail-shock, which increased stress-related behaviours. We found greater α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/N-methyl-d-aspartate current ratios and insertion of calcium-permeable AMPA receptors (AMPARs) in the OFC–BLA synapse after stress. These stress-induced synaptic and behavioural changes were reduced by a blockade of protein kinase A, which plays a principal role in stress-induced targeting of AMPARs into the synaptic membrane. To examine a possible causal relationship between alterations in synaptic transmission in the OFC–BLA pathway and stress-related behaviour, we performed optogenetic activation or chemogenetic inactivation of OFC–BLA transmission in mice. We found that optogenetic activation and chemogenetic inactivation of OFC–BLA transmission increased and decreased stress-related behaviour, respectively. In conclusion, we have demonstrated that stress altered the postsynaptic properties of the OFC–BLA pathway. These synaptic changes might be one of the underlying mechanisms of stress-induced behavioural alterations. |
format | Online Article Text |
id | pubmed-7235080 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-72350802020-05-20 Stress induces insertion of calcium-permeable AMPA receptors in the OFC–BLA synapse and modulates emotional behaviours in mice Kuniishi, Hiroshi Yamada, Daisuke Wada, Keiji Yamada, Mitsuhiko Sekiguchi, Masayuki Transl Psychiatry Article Stress increases the risk of neuropsychiatric disorders, such as major depression. Exposure to stress has been reported to induce various neuronal changes, such as alterations in synaptic transmission and structure. However, a causal link between stress-induced neural circuit alterations and changes in emotional behaviours is not well understood. In the present study, we focused on a projection pathway from the orbitofrontal cortex (OFC) to the basolateral nucleus of the amygdala (BLA) as a crucial circuit for negative emotions and examined the effect of stress on OFC–BLA excitatory synaptic transmission using optogenetic and whole-cell patch-clamp methods in mice. As a stress-inducing procedure, we used repeated tail-shock, which increased stress-related behaviours. We found greater α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/N-methyl-d-aspartate current ratios and insertion of calcium-permeable AMPA receptors (AMPARs) in the OFC–BLA synapse after stress. These stress-induced synaptic and behavioural changes were reduced by a blockade of protein kinase A, which plays a principal role in stress-induced targeting of AMPARs into the synaptic membrane. To examine a possible causal relationship between alterations in synaptic transmission in the OFC–BLA pathway and stress-related behaviour, we performed optogenetic activation or chemogenetic inactivation of OFC–BLA transmission in mice. We found that optogenetic activation and chemogenetic inactivation of OFC–BLA transmission increased and decreased stress-related behaviour, respectively. In conclusion, we have demonstrated that stress altered the postsynaptic properties of the OFC–BLA pathway. These synaptic changes might be one of the underlying mechanisms of stress-induced behavioural alterations. Nature Publishing Group UK 2020-05-18 /pmc/articles/PMC7235080/ /pubmed/32424318 http://dx.doi.org/10.1038/s41398-020-0837-3 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Kuniishi, Hiroshi Yamada, Daisuke Wada, Keiji Yamada, Mitsuhiko Sekiguchi, Masayuki Stress induces insertion of calcium-permeable AMPA receptors in the OFC–BLA synapse and modulates emotional behaviours in mice |
title | Stress induces insertion of calcium-permeable AMPA receptors in the OFC–BLA synapse and modulates emotional behaviours in mice |
title_full | Stress induces insertion of calcium-permeable AMPA receptors in the OFC–BLA synapse and modulates emotional behaviours in mice |
title_fullStr | Stress induces insertion of calcium-permeable AMPA receptors in the OFC–BLA synapse and modulates emotional behaviours in mice |
title_full_unstemmed | Stress induces insertion of calcium-permeable AMPA receptors in the OFC–BLA synapse and modulates emotional behaviours in mice |
title_short | Stress induces insertion of calcium-permeable AMPA receptors in the OFC–BLA synapse and modulates emotional behaviours in mice |
title_sort | stress induces insertion of calcium-permeable ampa receptors in the ofc–bla synapse and modulates emotional behaviours in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235080/ https://www.ncbi.nlm.nih.gov/pubmed/32424318 http://dx.doi.org/10.1038/s41398-020-0837-3 |
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