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The Suprachiasmatic Nucleus Regulates Anxiety-Like Behavior in Mice

Individuals suffering from mood and anxiety disorders often show significant disturbances in sleep and circadian rhythms. Animal studies indicate that circadian rhythm disruption can cause increased depressive- and anxiety-like behavior, but the underlying mechanisms are unclear. One potential mecha...

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Autores principales: Vadnie, Chelsea A., Petersen, Kaitlyn A., Eberhardt, Lauren A., Hildebrand, Mariah A., Cerwensky, Allison J., Zhang, Hui, Burns, Jennifer N., Becker-Krail, Darius D., DePoy, Lauren M., Logan, Ryan W., McClung, Colleen A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8811036/
https://www.ncbi.nlm.nih.gov/pubmed/35126036
http://dx.doi.org/10.3389/fnins.2021.765850
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author Vadnie, Chelsea A.
Petersen, Kaitlyn A.
Eberhardt, Lauren A.
Hildebrand, Mariah A.
Cerwensky, Allison J.
Zhang, Hui
Burns, Jennifer N.
Becker-Krail, Darius D.
DePoy, Lauren M.
Logan, Ryan W.
McClung, Colleen A.
author_facet Vadnie, Chelsea A.
Petersen, Kaitlyn A.
Eberhardt, Lauren A.
Hildebrand, Mariah A.
Cerwensky, Allison J.
Zhang, Hui
Burns, Jennifer N.
Becker-Krail, Darius D.
DePoy, Lauren M.
Logan, Ryan W.
McClung, Colleen A.
author_sort Vadnie, Chelsea A.
collection PubMed
description Individuals suffering from mood and anxiety disorders often show significant disturbances in sleep and circadian rhythms. Animal studies indicate that circadian rhythm disruption can cause increased depressive- and anxiety-like behavior, but the underlying mechanisms are unclear. One potential mechanism to explain how circadian rhythms are contributing to mood and anxiety disorders is through dysregulation of the suprachiasmatic nucleus (SCN) of the hypothalamus, known as the “central pacemaker.” To investigate the role of the SCN in regulating depressive- and anxiety-like behavior in mice, we chronically manipulated the neural activity of the SCN using two optogenetic stimulation paradigms. As expected, chronic stimulation of the SCN late in the active phase (circadian time 21, CT21) resulted in a shortened period and dampened amplitude of homecage activity rhythms. We also repeatedly stimulated the SCN at unpredictable times during the active phase of mice when SCN firing rates are normally low. This resulted in dampened, fragmented, and unstable homecage activity rhythms. In both chronic SCN optogenetic stimulation paradigms, dampened homecage activity rhythms (decreased amplitude) were directly correlated with increased measures of anxiety-like behavior. In contrast, we only observed a correlation between behavioral despair and homecage activity amplitude in mice stimulated at CT21. Surprisingly, the change in period of homecage activity rhythms was not directly associated with anxiety- or depressive-like behavior. Finally, to determine if anxiety-like behavior is affected during a single SCN stimulation session, we acutely stimulated the SCN in the active phase (zeitgeber time 14-16, ZT14-16) during behavioral testing. Unexpectedly this also resulted in increased anxiety-like behavior. Taken together, these results indicate that SCN-mediated dampening of rhythms is directly correlated with increased anxiety-like behavior. This work is an important step in understanding how specific SCN neural activity disruptions affect depressive- and anxiety-related behavior.
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spelling pubmed-88110362022-02-04 The Suprachiasmatic Nucleus Regulates Anxiety-Like Behavior in Mice Vadnie, Chelsea A. Petersen, Kaitlyn A. Eberhardt, Lauren A. Hildebrand, Mariah A. Cerwensky, Allison J. Zhang, Hui Burns, Jennifer N. Becker-Krail, Darius D. DePoy, Lauren M. Logan, Ryan W. McClung, Colleen A. Front Neurosci Neuroscience Individuals suffering from mood and anxiety disorders often show significant disturbances in sleep and circadian rhythms. Animal studies indicate that circadian rhythm disruption can cause increased depressive- and anxiety-like behavior, but the underlying mechanisms are unclear. One potential mechanism to explain how circadian rhythms are contributing to mood and anxiety disorders is through dysregulation of the suprachiasmatic nucleus (SCN) of the hypothalamus, known as the “central pacemaker.” To investigate the role of the SCN in regulating depressive- and anxiety-like behavior in mice, we chronically manipulated the neural activity of the SCN using two optogenetic stimulation paradigms. As expected, chronic stimulation of the SCN late in the active phase (circadian time 21, CT21) resulted in a shortened period and dampened amplitude of homecage activity rhythms. We also repeatedly stimulated the SCN at unpredictable times during the active phase of mice when SCN firing rates are normally low. This resulted in dampened, fragmented, and unstable homecage activity rhythms. In both chronic SCN optogenetic stimulation paradigms, dampened homecage activity rhythms (decreased amplitude) were directly correlated with increased measures of anxiety-like behavior. In contrast, we only observed a correlation between behavioral despair and homecage activity amplitude in mice stimulated at CT21. Surprisingly, the change in period of homecage activity rhythms was not directly associated with anxiety- or depressive-like behavior. Finally, to determine if anxiety-like behavior is affected during a single SCN stimulation session, we acutely stimulated the SCN in the active phase (zeitgeber time 14-16, ZT14-16) during behavioral testing. Unexpectedly this also resulted in increased anxiety-like behavior. Taken together, these results indicate that SCN-mediated dampening of rhythms is directly correlated with increased anxiety-like behavior. This work is an important step in understanding how specific SCN neural activity disruptions affect depressive- and anxiety-related behavior. Frontiers Media S.A. 2022-01-20 /pmc/articles/PMC8811036/ /pubmed/35126036 http://dx.doi.org/10.3389/fnins.2021.765850 Text en Copyright © 2022 Vadnie, Petersen, Eberhardt, Hildebrand, Cerwensky, Zhang, Burns, Becker-Krail, DePoy, Logan and McClung. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Vadnie, Chelsea A.
Petersen, Kaitlyn A.
Eberhardt, Lauren A.
Hildebrand, Mariah A.
Cerwensky, Allison J.
Zhang, Hui
Burns, Jennifer N.
Becker-Krail, Darius D.
DePoy, Lauren M.
Logan, Ryan W.
McClung, Colleen A.
The Suprachiasmatic Nucleus Regulates Anxiety-Like Behavior in Mice
title The Suprachiasmatic Nucleus Regulates Anxiety-Like Behavior in Mice
title_full The Suprachiasmatic Nucleus Regulates Anxiety-Like Behavior in Mice
title_fullStr The Suprachiasmatic Nucleus Regulates Anxiety-Like Behavior in Mice
title_full_unstemmed The Suprachiasmatic Nucleus Regulates Anxiety-Like Behavior in Mice
title_short The Suprachiasmatic Nucleus Regulates Anxiety-Like Behavior in Mice
title_sort suprachiasmatic nucleus regulates anxiety-like behavior in mice
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8811036/
https://www.ncbi.nlm.nih.gov/pubmed/35126036
http://dx.doi.org/10.3389/fnins.2021.765850
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