This study investigates the role of microglia in the extinction of anxiety-like behaviors induced by acute restraint stress in male mice. Acute restraint stress increases GABAergic neuron activity in the central nucleus of the amygdala (CeA), leading to anxiety-like behaviors within 12 hours. This increased activity triggers the secretion of CX3CL1 via the MST4-NF-κB-CX3CL1 signaling pathway, which activates microglia in the CeA. Activated microglia then engulf dendritic spines of GABAergic neurons, reducing their activity and leading to the extinction of anxiety-like behaviors. These findings reveal a microglia-driven negative feedback mechanism that helps maintain brain homeostasis after acute stress. The study also shows that microglial activation is involved in the extinction of anxiety-like behaviors, with microglial engulfment of GABAergic neuronal spines playing a key role. The MST4-NF-κB-CX3CL1 signaling pathway is crucial for this process, as MST4 expression decreases in GABAergic neurons after acute stress, leading to increased CX3CL1 secretion and microglial activation. The study further demonstrates that MST4 overexpression in GABAergic neurons reduces anxiety-like behaviors by inhibiting microglial activation and neuronal spine engulfment. These results highlight the importance of microglial activity in the extinction of anxiety-like behaviors following acute stress.This study investigates the role of microglia in the extinction of anxiety-like behaviors induced by acute restraint stress in male mice. Acute restraint stress increases GABAergic neuron activity in the central nucleus of the amygdala (CeA), leading to anxiety-like behaviors within 12 hours. This increased activity triggers the secretion of CX3CL1 via the MST4-NF-κB-CX3CL1 signaling pathway, which activates microglia in the CeA. Activated microglia then engulf dendritic spines of GABAergic neurons, reducing their activity and leading to the extinction of anxiety-like behaviors. These findings reveal a microglia-driven negative feedback mechanism that helps maintain brain homeostasis after acute stress. The study also shows that microglial activation is involved in the extinction of anxiety-like behaviors, with microglial engulfment of GABAergic neuronal spines playing a key role. The MST4-NF-κB-CX3CL1 signaling pathway is crucial for this process, as MST4 expression decreases in GABAergic neurons after acute stress, leading to increased CX3CL1 secretion and microglial activation. The study further demonstrates that MST4 overexpression in GABAergic neurons reduces anxiety-like behaviors by inhibiting microglial activation and neuronal spine engulfment. These results highlight the importance of microglial activity in the extinction of anxiety-like behaviors following acute stress.