Distinct subcircuits within the mesolimbic dopamine system encode the salience and valence of social stimuli

Rationale: The mesolimbic dopamine (DA) system (MDS) is the canonical “reward” pathway that has been studied extensively in the context of the rewarding properties of food and drugs of abuse. In contrast, little is known about the role of the MDS in the processing of the rewarding and aversive properties of social stimuli. Objective: Social interactions can be characterized by their salience (i.e., importance) and their rewarding or aversive properties (i.e., valence). Here, we test the novel hypothesis that projections from the medial ventral tegmental area (VTA) to the nucleus accumbens (NAc) core code the salience of social stimuli through phasic release of DA in response to rewarding and aversive social stimuli. In contrast, lateral VTA (lVTA) projections to the NAc shell are proposed to encode social valence, with increased tonic DA signaling rewarding interactions and decreased tonic DA signaling aversive ones. Methods: Using DA amperometry, which monitors DA signaling with a high degree of temporal and anatomical resolution, we measured DA release in the NAc core or shell during rewarding and aversive social interactions. Anatomical and functional studies were conducted utilizing retrograde tracing and immunohistochemistry. Results: These studies support the hypothesis that distinct MDS subcircuits (i.e., mVTA to NAc core and lVTA to NAc shell) signal the salience and valence, respectively, of social stimuli. Conclusion: Together, these data provide a novel conceptualization of how functional and anatomical heterogeneity within the MDS detect and distinguish between social salience, social reward, and social aversion.