Glucocorticoid receptor-mediated amygdalar metaplasticity underlies adaptive modulation of fear memory by stress
Glucocorticoid receptor (GR) is crucial for signaling mediated by stress-induced high levels of glucocorticoids. The lateral nucleus of the amygdala (LA) is a key structure underlying auditory-cued fear conditioning. Here, we demonstrate that genetic disruption of GR in the LA (LAGRKO) resulted in a...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/34135 |
| _version_ | 1811199369043509248 |
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| author | Ran Inoue Kareem Abdou Ayumi Hayashi-Tanaka Shin-ichi Muramatsu Kaori Mino Kaoru Inokuchi Hisashi Mori |
| author_facet | Ran Inoue Kareem Abdou Ayumi Hayashi-Tanaka Shin-ichi Muramatsu Kaori Mino Kaoru Inokuchi Hisashi Mori |
| author_sort | Ran Inoue |
| collection | DOAJ |
| description | Glucocorticoid receptor (GR) is crucial for signaling mediated by stress-induced high levels of glucocorticoids. The lateral nucleus of the amygdala (LA) is a key structure underlying auditory-cued fear conditioning. Here, we demonstrate that genetic disruption of GR in the LA (LAGRKO) resulted in an auditory-cued fear memory deficit for strengthened conditioning. Furthermore, the suppressive effect of a single restraint stress (RS) prior to conditioning on auditory-cued fear memory in floxed GR (control) mice was abolished in LAGRKO mice. Optogenetic induction of long-term depression (LTD) at auditory inputs to the LA reduced auditory-cued fear memory in RS-exposed LAGRKO mice, and in contrast, optogenetic induction of long-term potentiation (LTP) increased auditory-cued fear memory in RS-exposed floxed GR mice. These findings suggest that prior stress suppresses fear conditioning-induced LTP at auditory inputs to the LA in a GR-dependent manner, thereby protecting animals from encoding excessive cued fear memory under stress conditions. |
| first_indexed | 2024-04-12T01:47:06Z |
| format | Article |
| id | doaj.art-3695be2dbfc246808515e84d4cdce54d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:47:06Z |
| publishDate | 2018-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-3695be2dbfc246808515e84d4cdce54d2022-12-22T03:53:02ZengeLife Sciences Publications LtdeLife2050-084X2018-06-01710.7554/eLife.34135Glucocorticoid receptor-mediated amygdalar metaplasticity underlies adaptive modulation of fear memory by stressRan Inoue0https://orcid.org/0000-0003-0700-7734Kareem Abdou1Ayumi Hayashi-Tanaka2Shin-ichi Muramatsu3https://orcid.org/0000-0002-3185-7790Kaori Mino4Kaoru Inokuchi5https://orcid.org/0000-0002-5393-3133Hisashi Mori6https://orcid.org/0000-0001-9743-2456Department of Molecular Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, JapanDepartment of Biochemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan; Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, EgyptDepartment of Molecular Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, JapanDivision of Neurology, Department of Medicine, Jichi Medical University, Tochigi, Japan; Center for Gene and Cell Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, JapanDepartment of Molecular Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, JapanDepartment of Biochemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, JapanDepartment of Molecular Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, JapanGlucocorticoid receptor (GR) is crucial for signaling mediated by stress-induced high levels of glucocorticoids. The lateral nucleus of the amygdala (LA) is a key structure underlying auditory-cued fear conditioning. Here, we demonstrate that genetic disruption of GR in the LA (LAGRKO) resulted in an auditory-cued fear memory deficit for strengthened conditioning. Furthermore, the suppressive effect of a single restraint stress (RS) prior to conditioning on auditory-cued fear memory in floxed GR (control) mice was abolished in LAGRKO mice. Optogenetic induction of long-term depression (LTD) at auditory inputs to the LA reduced auditory-cued fear memory in RS-exposed LAGRKO mice, and in contrast, optogenetic induction of long-term potentiation (LTP) increased auditory-cued fear memory in RS-exposed floxed GR mice. These findings suggest that prior stress suppresses fear conditioning-induced LTP at auditory inputs to the LA in a GR-dependent manner, thereby protecting animals from encoding excessive cued fear memory under stress conditions.https://elifesciences.org/articles/34135glucocorticoid receptormetaplasticitylateral amygdalaauditory fear conditioningstress |
| spellingShingle | Ran Inoue Kareem Abdou Ayumi Hayashi-Tanaka Shin-ichi Muramatsu Kaori Mino Kaoru Inokuchi Hisashi Mori Glucocorticoid receptor-mediated amygdalar metaplasticity underlies adaptive modulation of fear memory by stress eLife glucocorticoid receptor metaplasticity lateral amygdala auditory fear conditioning stress |
| title | Glucocorticoid receptor-mediated amygdalar metaplasticity underlies adaptive modulation of fear memory by stress |
| title_full | Glucocorticoid receptor-mediated amygdalar metaplasticity underlies adaptive modulation of fear memory by stress |
| title_fullStr | Glucocorticoid receptor-mediated amygdalar metaplasticity underlies adaptive modulation of fear memory by stress |
| title_full_unstemmed | Glucocorticoid receptor-mediated amygdalar metaplasticity underlies adaptive modulation of fear memory by stress |
| title_short | Glucocorticoid receptor-mediated amygdalar metaplasticity underlies adaptive modulation of fear memory by stress |
| title_sort | glucocorticoid receptor mediated amygdalar metaplasticity underlies adaptive modulation of fear memory by stress |
| topic | glucocorticoid receptor metaplasticity lateral amygdala auditory fear conditioning stress |
| url | https://elifesciences.org/articles/34135 |
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