Mesocorticolimbic circuit mechanisms of social dominance behavior

초록

Social animals compete for limited resources, resulting in a social hierarchy. Although different neuronal subpopulations in the medial prefrontal cortex (mPFC), which has been mechanistically implicated in social dominance behavior, encode distinct social competition behaviors, their identities and associated molecular underpinnings have not yet been identified. In this study, we found that mPFC neurons projecting to the nucleus accumbens (mPFC-NAc) encode social winning behavior, whereas mPFC neurons projecting to the ventral tegmental area (mPFC-VTA) encode social losing behavior. High-throughput single-cell transcriptomic analysis and projection-specific genetic manipulation revealed that the expression level of POU domain, class 3, transcription factor 1 (Pou3f1) in mPFC-VTA neurons controls social hierarchy. Optogenetic activation of mPFC-VTA neurons increases Pou3f1 expression and lowers social rank. Together, these data demonstrate that discrete activity and gene expression in separate mPFC projections oppositely orchestrate social competition and hierarchy. Next, we are elucidating cell type- and projection-specific contributions to social hierarchy in the VTA to determine whether the primary driving force behind social hierarchy is the motivation and reward system regulated by the mesocorticolimbic dopaminergic pathway. Our findings indicate that inhibition of dopaminergic or GABAergic neurons in the VTA (VTADA or VTAGABA) respectively decreases or increases social hierarchy. Moreover, inhibition of VTADA projecting to the NAc (VTADA-NAc) decreases social hierarchy, whereas inhibition of VTADA projecting to the mPFC (VTADA-mPFC) increases social hierarchy. These results suggest that social hierarchy is differentially regulated by distinct cell types in the VTA and by specific VTADA projections.