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VTA-projecting cerebellar neurons mediate stress-dependent depression-like behaviors
Although cerebellar alterations have been implicated in stress symptoms, the exact contribution of the cerebellum to stress symptoms remains to be elucidated. Here, we demonstrated the crucial role of cerebellar neurons projecting to the ventral tegmental area (VTA) in the development of chronic str...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8843095/ https://www.ncbi.nlm.nih.gov/pubmed/35156922 http://dx.doi.org/10.7554/eLife.72981 |
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author | Baek, Soo Ji Park, Jin Sung Kim, Jinhyun Yamamoto, Yukio Tanaka-Yamamoto, Keiko |
author_facet | Baek, Soo Ji Park, Jin Sung Kim, Jinhyun Yamamoto, Yukio Tanaka-Yamamoto, Keiko |
author_sort | Baek, Soo Ji |
collection | PubMed |
description | Although cerebellar alterations have been implicated in stress symptoms, the exact contribution of the cerebellum to stress symptoms remains to be elucidated. Here, we demonstrated the crucial role of cerebellar neurons projecting to the ventral tegmental area (VTA) in the development of chronic stress-induced behavioral alterations in mice. Chronic chemogenetic activation of inhibitory Purkinje cells in crus I suppressed c-Fos expression in the DN and an increase in immobility in the tail suspension test or forced swimming test, which were triggered by chronic stress application. The combination of adeno-associated virus-based circuit mapping and electrophysiological recording identified network connections from crus I to the VTA via the dentate nucleus (DN) of the deep cerebellar nuclei. Furthermore, chronic inhibition of specific neurons in the DN that project to the VTA prevented stressed mice from showing such depression-like behavior, whereas chronic activation of these neurons alone triggered behavioral changes that were comparable with the depression-like behaviors triggered by chronic stress application. Our results indicate that the VTA-projecting cerebellar neurons proactively regulate the development of depression-like behavior, raising the possibility that cerebellum may be an effective target for the prevention of depressive disorders in human. |
format | Online Article Text |
id | pubmed-8843095 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-88430952022-02-16 VTA-projecting cerebellar neurons mediate stress-dependent depression-like behaviors Baek, Soo Ji Park, Jin Sung Kim, Jinhyun Yamamoto, Yukio Tanaka-Yamamoto, Keiko eLife Neuroscience Although cerebellar alterations have been implicated in stress symptoms, the exact contribution of the cerebellum to stress symptoms remains to be elucidated. Here, we demonstrated the crucial role of cerebellar neurons projecting to the ventral tegmental area (VTA) in the development of chronic stress-induced behavioral alterations in mice. Chronic chemogenetic activation of inhibitory Purkinje cells in crus I suppressed c-Fos expression in the DN and an increase in immobility in the tail suspension test or forced swimming test, which were triggered by chronic stress application. The combination of adeno-associated virus-based circuit mapping and electrophysiological recording identified network connections from crus I to the VTA via the dentate nucleus (DN) of the deep cerebellar nuclei. Furthermore, chronic inhibition of specific neurons in the DN that project to the VTA prevented stressed mice from showing such depression-like behavior, whereas chronic activation of these neurons alone triggered behavioral changes that were comparable with the depression-like behaviors triggered by chronic stress application. Our results indicate that the VTA-projecting cerebellar neurons proactively regulate the development of depression-like behavior, raising the possibility that cerebellum may be an effective target for the prevention of depressive disorders in human. eLife Sciences Publications, Ltd 2022-02-14 /pmc/articles/PMC8843095/ /pubmed/35156922 http://dx.doi.org/10.7554/eLife.72981 Text en © 2022, Baek et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Neuroscience Baek, Soo Ji Park, Jin Sung Kim, Jinhyun Yamamoto, Yukio Tanaka-Yamamoto, Keiko VTA-projecting cerebellar neurons mediate stress-dependent depression-like behaviors |
title | VTA-projecting cerebellar neurons mediate stress-dependent depression-like behaviors |
title_full | VTA-projecting cerebellar neurons mediate stress-dependent depression-like behaviors |
title_fullStr | VTA-projecting cerebellar neurons mediate stress-dependent depression-like behaviors |
title_full_unstemmed | VTA-projecting cerebellar neurons mediate stress-dependent depression-like behaviors |
title_short | VTA-projecting cerebellar neurons mediate stress-dependent depression-like behaviors |
title_sort | vta-projecting cerebellar neurons mediate stress-dependent depression-like behaviors |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8843095/ https://www.ncbi.nlm.nih.gov/pubmed/35156922 http://dx.doi.org/10.7554/eLife.72981 |
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