Projection-specific role of PFC neurons in social hierachy

초록

Social competition among individuals within the group, such as for limited resources, space, and mating opportunities, forms social hierarchies. This serves as an evolutionarily conserved behavioral pattern to prevent excessive competition between individuals and to maintain group stability. It has been reported that the medial prefrontal cortex (mPFC) has been identified as a key brain region involved in the recognition and formation of social hierarchies and that two major components of the mesolimbic system, the nucleus accumbens (NAc) and ventral tegmental area (VTA), are involved in this behavior. However, the detailed neural circuit and molecular mechanisms underlying the formation and maintenance of social hierarchies due to social competition remain largely unclear. In this study, we found that mPFC neurons projecting to the NAc (mPFC-NAc) encode social winning behavior, whereas mPFC neurons projecting to the VTA (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.