State-dependent reward circuit modulation gates social buffering of stress

Social experiences can profoundly shape emotional regulation and promote resilience to stress. Although the presence of companions is well-known to buffer the impact of stress in humans and rodents^1-5, whether and how social interactions restore the disruptions in reward processing commonly produced by stress remains unknown. Here, we developed a reward-based behavioral paradigm to study social buffering. Brief interaction with a familiar, unstressed partner following acute restraint stress restored reward-seeking behavior in both female and male C57BL6/J mice. Our findings indicate that buffering is an active process driven by the stressed individual, rather than a passive outcome of social interaction. Ventral tegmental area (VTA) GABAergic, but not dopaminergic, neurons play a key role in mediating this effect. Critically, temporally precise inhibition of VTA GABA neuron activity is sufficient to convert a non-buffering interaction with a novel partner into a buffering experience, whereas identical inhibition delivered outside of a social context is ineffective. These results reveal a previously unrecognized role for socially elicited VTA GABA neuron activity in gating the response to stress and position the stressed individual's behavior as a key determinant of resilience. Given the central role of stress-induced reward deficits in psychiatric disorders, these findings have broad implications for understanding resilience and the development of novel therapies.