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Sex-specific adaptations to VTA circuits following subchronic stress

Dysregulation of the mesolimbic reward circuitry is implicated in the pathophysiology of stress-related illnesses such as depression and anxiety. These disorders are more frequently diagnosed in females, and sex differences in the response to stress are likely to be one factor that leads to enhanced...

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Autores principales: Bouarab, Chloé, Wynalda, Megan, Thompson, Brittney V., Khurana, Ambika, Cody, Caitlyn R., Kisner, Alexandre, Polter, Abigail M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418168/
https://www.ncbi.nlm.nih.gov/pubmed/37577542
http://dx.doi.org/10.1101/2023.08.02.551665
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author Bouarab, Chloé
Wynalda, Megan
Thompson, Brittney V.
Khurana, Ambika
Cody, Caitlyn R.
Kisner, Alexandre
Polter, Abigail M.
author_facet Bouarab, Chloé
Wynalda, Megan
Thompson, Brittney V.
Khurana, Ambika
Cody, Caitlyn R.
Kisner, Alexandre
Polter, Abigail M.
author_sort Bouarab, Chloé
collection PubMed
description Dysregulation of the mesolimbic reward circuitry is implicated in the pathophysiology of stress-related illnesses such as depression and anxiety. These disorders are more frequently diagnosed in females, and sex differences in the response to stress are likely to be one factor that leads to enhanced vulnerability of females. In this study, we use subchronic variable stress (SCVS), a model in which females are uniquely vulnerable to behavioral disturbances, to investigate sexually divergent mechanisms of regulation of the ventral tegmental area by stress. Using slice electrophysiology, we find that female, but not male mice have a reduction in the ex vivo firing rate of VTA dopaminergic neurons following SCVS. Surprisingly, both male and female animals show an increase in inhibitory tone onto VTA dopaminergic neurons and an increase in the firing rate of VTA GABAergic neurons. In males, however, this is accompanied by a robust increase in excitatory synaptic tone onto VTA dopamine neurons. This supports a model by which SCVS recruits VTA GABA neurons to inhibit dopaminergic neurons in both male and female mice, but males are protected from diminished functioning of the dopaminergic system by a compensatory upregulation of excitatory synapses.
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spelling pubmed-104181682023-08-12 Sex-specific adaptations to VTA circuits following subchronic stress Bouarab, Chloé Wynalda, Megan Thompson, Brittney V. Khurana, Ambika Cody, Caitlyn R. Kisner, Alexandre Polter, Abigail M. bioRxiv Article Dysregulation of the mesolimbic reward circuitry is implicated in the pathophysiology of stress-related illnesses such as depression and anxiety. These disorders are more frequently diagnosed in females, and sex differences in the response to stress are likely to be one factor that leads to enhanced vulnerability of females. In this study, we use subchronic variable stress (SCVS), a model in which females are uniquely vulnerable to behavioral disturbances, to investigate sexually divergent mechanisms of regulation of the ventral tegmental area by stress. Using slice electrophysiology, we find that female, but not male mice have a reduction in the ex vivo firing rate of VTA dopaminergic neurons following SCVS. Surprisingly, both male and female animals show an increase in inhibitory tone onto VTA dopaminergic neurons and an increase in the firing rate of VTA GABAergic neurons. In males, however, this is accompanied by a robust increase in excitatory synaptic tone onto VTA dopamine neurons. This supports a model by which SCVS recruits VTA GABA neurons to inhibit dopaminergic neurons in both male and female mice, but males are protected from diminished functioning of the dopaminergic system by a compensatory upregulation of excitatory synapses. Cold Spring Harbor Laboratory 2023-08-02 /pmc/articles/PMC10418168/ /pubmed/37577542 http://dx.doi.org/10.1101/2023.08.02.551665 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Bouarab, Chloé
Wynalda, Megan
Thompson, Brittney V.
Khurana, Ambika
Cody, Caitlyn R.
Kisner, Alexandre
Polter, Abigail M.
Sex-specific adaptations to VTA circuits following subchronic stress
title Sex-specific adaptations to VTA circuits following subchronic stress
title_full Sex-specific adaptations to VTA circuits following subchronic stress
title_fullStr Sex-specific adaptations to VTA circuits following subchronic stress
title_full_unstemmed Sex-specific adaptations to VTA circuits following subchronic stress
title_short Sex-specific adaptations to VTA circuits following subchronic stress
title_sort sex-specific adaptations to vta circuits following subchronic stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418168/
https://www.ncbi.nlm.nih.gov/pubmed/37577542
http://dx.doi.org/10.1101/2023.08.02.551665
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