Distinct prefrontal projection activity and transcriptional state conversely orchestrate social competition and hierarchy.

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.