Distinct prefrontal projections conversely orchestrate social competition and hierarchy

Abstract

SummarySocial animals compete for limited resources, resulting in a social hierarchy. Although different neuronal subpopulations in the medial prefrontal cortex (mPFC), a hub brain region of social hierarchy, 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 by monitoring and manipulating neural circuit activity. 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 increasesPou3f1expression and lowers social rank. Together, these data demonstrate that discrete activity and gene expression in separate mPFC projections oppositely orchestrate social competition and hierarchy.

Dissociable roles of the mPFC-to-VTA Pathway in the control of iImpulsive Action and Risk-Related Decision-Making in Roman High- And Low-Avoidance Rats

“…One potential explanation for these differences is the relative density of projections within each specific pathway. While a precise quantification is currently lacking, it is reasonable to estimate that less than 20% of the mPFC neurons project to the VTA (Choi et al, 2024), compared to over 70% of the substantia nigra DA neurons projecting to the striatum (Chen et al, 2022). Thus, greater projection densities within the nigrostriatal pathway might have contributed to stronger/detectable brain metabolic changes.…”