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© 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

The mechanisms of anxiety disorders, the most common mental illness, remain incompletely characterized. The ventral hippocampus (vHPC) is critical for the expression of anxiety. However, current studies primarily focus on vHPC neurons, leaving the role for vHPC astrocytes in anxiety largely unexplored. Here, genetically encoded Ca2+ indicator GCaMP6m and in vivo fiber photometry calcium imaging are used to label vHPC astrocytes and monitor their activity, respectively, genetic and chemogenetic approaches to inhibit and activate vHPC astrocytes, respectively, patch‐clamp recordings to measure glutamate currents, and behavioral assays to assess anxiety‐like behaviors. It is found that vHPC astrocytic activity is increased in anxiogenic environments and by 3‐d subacute restraint stress (SRS), a well‐validated mouse model of anxiety disorders. Genetic inhibition of vHPC astrocytes exerts anxiolytic effects on both innate and SRS‐induced anxiety‐related behaviors, whereas hM3Dq‐mediated chemogenetic or SRS‐induced activation of vHPC astrocytes enhances anxiety‐like behaviors, which are reversed by intra‐vHPC application of the ionotropic glutamate N‐methyl‐d‐aspartate receptor antagonists. Furthermore, intra‐vHPC or systemic application of the N‐methyl‐d‐aspartate receptor antagonist memantine, a U.S. FDA‐approved drug for Alzheimer's disease, fully rescues SRS‐induced anxiety‐like behaviors. The findings highlight vHPC astrocytes as critical regulators of stress and anxiety and as potential therapeutic targets for anxiety and anxiety‐related disorders.

Details

Title
Astrocytes in the Ventral Hippocampus Bidirectionally Regulate Innate and Stress‐Induced Anxiety‐Like Behaviors in Male Mice
Author
Li, Jing‐Ting 1 ; Jin, Shi‐Yang 1 ; Hu, Jian 1 ; Xu, Ru‐Xia 1 ; Xu, Jun‐Nan 1 ; Li, Zi‐Ming 1 ; Wang, Meng‐Ling 1 ; Fu, Yi‐Wen 1 ; Liao, Shi‐Han 1 ; Li, Xiao‐Wen 1 ; Chen, Yi‐Hua 1 ; Gao, Tian‐Ming 1 ; Yang, Jian‐Ming 1   VIAFID ORCID Logo 

 State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong‐Hong Kong‐Macao Greater Bay Area Center for Brain Science and Brain‐Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China 
Section
Research Article
Publication year
2024
Publication date
Oct 1, 2024
Publisher
John Wiley & Sons, Inc.
e-ISSN
21983844
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3117020432
Copyright
© 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.