GABA signaling in NG2 glia mediates empathy-like behavior under observational social defeat

Empathy, ranging from emotional contagion to consolation, is central to social cognition. While neural mechanisms of observed pain are well studied, how witnessing trauma affects empathy-related behaviors remains unclear. Using an observational social defeat (OSD) model, we find that OSD-exposed mice display enhanced allogrooming toward defeated conspecifics, indicating increased consolation behavior. Whole-brain cFos mapping and fiber photometry reveal selective activation of medial amygdala (MeA) GABAergic neurons during empathic allogrooming. NG2 glia modulate this behavior via GABA signaling; their specific ablation in the MeA reduces inhibitory synaptic transmission, disinhibiting neighboring GABAergic neurons and increasing allogrooming. Single-cell RNA analysis reveals that GABA signaling originates from Gad1-expressing NG2 glia. Genetic knockout of Gad1 in NG2 glia recapitulates the phenotype. This mechanism requires elevated corticosterone induced by social defeat. Our findings highlight the role of NG2 glia-GABA neuron interactions in promoting prosocial empathy and suggest targeting GABA signaling in NG2 glia as a potential therapeutic strategy for vicarious trauma. Using an observational social defeat model, here authors show NG2 glia in the medial amygdala of observer mice attenuate GABA synthesis and reduce inhibitory tone onto neighboring GABAergic neurons, thereby driving empathy-like allogrooming toward distressed companions.