Prefrontal and Subcortical c-Fos Mapping of Reward Responses across Competitive and Social Contexts

Caroline De Paula Cunha Almeida,Meghan Cum,Elizabeth Illescas-Huerta,Amelia R. Chambers,Charles Ye,A. Shah,Ayush Jain,Albert Li,Nancy Padilla-Coreano

Published 2025 in eNeuro

ABSTRACT

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 nonsocial reward contexts. Noncompetitive 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.

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