Anterior Cingulate Cortex Mediates State-Dependent Prioritization of Distressed Conspecifics

Background/Objectives: Emotion recognition is a fundamental component of mammalian social cognition, enabling animals such as rodents to detect the emotional states of conspecifics and guide prosocial or avoidance behaviors. However, natural social landscapes are highly complex and multi-targeted. Furthermore, it remains unknown how an observer’s own internal emotional state dictates social target prioritization in these dynamic environments. Methods: We used a novel multi-target social paradigm wherein observer mice subjected to naïve, positive (relieved), or negative (acute stress) experiences, interacting simultaneously with demonstrator mice in neutral, relieved, or stressed states. We utilized in vivo fiber photometry to record anterior cingulate cortex (ACC) calcium dynamics during these complex interactions, and employed bidirectional optogenetics to establish causal neural mechanisms. Results: Naïve and relieved observer mice exhibited a rapid, innate behavioral prioritization of acutely stressed conspecifics. Conversely, an internal state of acute stress experience in the observer completely abolished this early-stage discrimination. Fiber photometry revealed that ACC excitatory neuronal activity robustly encodes the prioritization of stressed conspecifics, a neural signature that is fundamentally suppressed in stressed observers. Optogenetic inhibition of the ACC abolished innate social preference in naïve and relieved mice, whereas targeted ACC activation successfully overrode internal stress to restore social discrimination in stressed observers. Conclusions: Acute negative internal states profoundly suppress social discrimination ability. The ACC acts as a state-dependent gatekeeper to dictate social prioritization.