Prefrontal and subcortical c-Fos mapping of reward responses across competitive and social contexts

Social animals compete for rewards to survive, yet the neural circuits underlying reward-based social competition remain unclear. The medial prefrontal cortex (mPFC) plays a key role in reward processing and social dominance, but whether its subregions contribute differently to competitions for reward remains unknown. Using c-Fos mapping in male CD1 mice, we examined reward-induced neural activation in mPFC subregions and key interconnected subcortical areas across social and non-social reward contexts. Non-competitive social contexts produced global c-Fos activation relative to competitive contexts. Cross-regional correlation analyses revealed that receiving rewards in isolation involved widespread network coordination, while social contexts exhibited distinct, sparse correlation patterns. Surprisingly, social rank effects on neural activity were most pronounced during isolated reward experiences rather than during competition, with dominant mice showing increased anterior cingulate, basolateral amygdala, and hippocampal activation when alone. Different dominance ranks (reward-based, territorial, and agonistic) correlated with distinct neural activity patterns across contexts. Overall, our results show that social context fundamentally reorganizes prefrontal-subcortical networks during reward processing in a social rank-dependent manner. These results provide new insights into how social rank shapes the neural basis of reward processing across different social contexts. Significance Statement: Social competition for rewards is fundamental for the survival of social species, yet the neural circuits supporting it remain poorly understood. We use mice to show that medial prefrontal cortex subregions and interconnected subcortical areas exhibit distinct activation and correlations depending on the social context in which the rewards are obtained. Social rank in mice influenced neural activation patterns, with subordinate mice showing increased activation in subcortical regions during exposure to non-competitive rewards. These findings highlight that reward processing in key subcortical regions within and connected to the mPFC are shaped by social context and hierarchy, providing insight into the neural mechanisms underlying social competition.