This study investigates the mechanisms underlying the extinction of anxiety-like behaviors induced by acute stress in male mice. Acute restraint stress increases the activity of GABAergic neurons in the central nucleus of the amygdala (CeA), leading to anxiety-like behaviors within 12 hours. This increase in GABAergic neuronal activity triggers microglial activation via the MST4-NF-κB-CX3CL1 signaling pathway, which subsequently activates microglia in the CeA. Activated microglia then inhibit GABAergic neuronal activity by engulfing their dendritic spines, reducing anxiety-like behaviors. The findings reveal a dynamic molecular and cellular mechanism where microglia drive a negative feedback loop to inhibit GABAergic neuronal activity, facilitating the maintenance of brain homeostasis in response to acute stress. The study provides insights into the role of microglia in the extinction of anxiety-like behaviors and suggests potential intervention strategies for treating stress-induced brain remodeling.This study investigates the mechanisms underlying the extinction of anxiety-like behaviors induced by acute stress in male mice. Acute restraint stress increases the activity of GABAergic neurons in the central nucleus of the amygdala (CeA), leading to anxiety-like behaviors within 12 hours. This increase in GABAergic neuronal activity triggers microglial activation via the MST4-NF-κB-CX3CL1 signaling pathway, which subsequently activates microglia in the CeA. Activated microglia then inhibit GABAergic neuronal activity by engulfing their dendritic spines, reducing anxiety-like behaviors. The findings reveal a dynamic molecular and cellular mechanism where microglia drive a negative feedback loop to inhibit GABAergic neuronal activity, facilitating the maintenance of brain homeostasis in response to acute stress. The study provides insights into the role of microglia in the extinction of anxiety-like behaviors and suggests potential intervention strategies for treating stress-induced brain remodeling.