Microglia govern the extinction of acute stress-induced anxiety-like behaviors in male mice

Danyang Chen, Qianqian Lou, Xiang-Jie Song, Fang Kang, An Liu, Changjian Zheng, Yanhua Li, Di Wang, Sen Qun, Zhi Zhang (), Peng Cao () and Yan Jin ()
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Danyang Chen: University of Science and Technology of China
Qianqian Lou: University of Science and Technology of China
Xiang-Jie Song: University of Science and Technology of China
Fang Kang: University of Science and Technology of China
An Liu: Anhui Medical University
Changjian Zheng: the First Affiliated Hospital of Wannan Medical College
Yanhua Li: University of Science and Technology of China
Di Wang: University of Science and Technology of China
Sen Qun: University of Science and Technology of China
Zhi Zhang: University of Science and Technology of China
Peng Cao: University of Science and Technology of China
Yan Jin: University of Science and Technology of China

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Anxiety-associated symptoms following acute stress usually become extinct gradually within a period of time. However, the mechanisms underlying how individuals cope with stress to achieve the extinction of anxiety are not clear. Here we show that acute restraint stress causes an increase in the activity of GABAergic neurons in the CeA (GABACeA) in male mice, resulting in anxiety-like behaviors within 12 hours; meanwhile, elevated GABACeA neuronal CX3CL1 secretion via MST4 (mammalian sterile-20-like kinase 4)-NF-κB-CX3CL1 signaling consequently activates microglia in the CeA. Activated microglia in turn inhibit GABACeA neuronal activity via the engulfment of their dendritic spines, ultimately leading to the extinction of anxiety-like behaviors induced by restraint stress. These findings reveal a dynamic molecular and cellular mechanism in which microglia drive a negative feedback to inhibit GABACeA neuronal activity, thus facilitating maintenance of brain homeostasis in response to acute stress.

Date: 2024
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DOI: 10.1038/s41467-024-44704-6

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