The study investigates the role of midbrain dopamine (DA) neurons in the ventral tegmental area (VTA) in mediating stress responses and susceptibility to social stress-induced behavioral abnormalities. The authors use optogenetics to manipulate the firing patterns of VTA DA neurons, specifically focusing on phasic firing, which is known to encode reward signals. They find that optogenetic induction of phasic firing in VTA DA neurons during a subthreshold social defeat paradigm rapidly induces a susceptible phenotype characterized by social avoidance and decreased sucrose preference. This effect is specific to phasic firing and not tonic firing. The study also reveals that the VTA-NAc pathway, but not the VTA-mPFC pathway, is involved in promoting susceptibility to social defeat stress. Specifically, optogenetic activation of the VTA-NAc pathway increases susceptibility, while inhibition of this pathway induces resilience. These findings provide novel insights into the mechanisms by which VTA DA neurons regulate stress responses and depression-like behaviors.The study investigates the role of midbrain dopamine (DA) neurons in the ventral tegmental area (VTA) in mediating stress responses and susceptibility to social stress-induced behavioral abnormalities. The authors use optogenetics to manipulate the firing patterns of VTA DA neurons, specifically focusing on phasic firing, which is known to encode reward signals. They find that optogenetic induction of phasic firing in VTA DA neurons during a subthreshold social defeat paradigm rapidly induces a susceptible phenotype characterized by social avoidance and decreased sucrose preference. This effect is specific to phasic firing and not tonic firing. The study also reveals that the VTA-NAc pathway, but not the VTA-mPFC pathway, is involved in promoting susceptibility to social defeat stress. Specifically, optogenetic activation of the VTA-NAc pathway increases susceptibility, while inhibition of this pathway induces resilience. These findings provide novel insights into the mechanisms by which VTA DA neurons regulate stress responses and depression-like behaviors.