Brain-Wide Subnetworks within and between Naturally Socializing Typical and Autism Model Mice

Abstract Social interaction is inherently asymmetric, requiring coordinated activity between non-homologous brain regions across individuals. However, the brain-wide dynamics underlying such inter-brain coordination remain poorly understood. We used multi-fiber photometry to simultaneously record from 24 brain regions in pairs of freely interacting mice, including a model of autism. Social interactions evoked widespread, dynamic activity across brains, with inter-brain synchrony, especially between non-homologous areas, exceeding intra-brain synchrony, particularly in dominant mice. Network analysis revealed three subnetworks: (1) Emotional, intra-brain enhanced in subordinates; (2) Sensory, spanning both mice; (3) Decision/consolidation, linking dominant prefrontal cortex to subordinate hippocampus. These subnetworks encoded dominance, identity, and interaction roles, and followed a clear temporal sequence around social events. In an autism model, socially evoked activity was hyperactive displaying mostly within brain synchrony but lacked inter-brain synchrony. Our results uncover dynamic inter-brain circuits as a hallmark of social behavior and reveal their disruption in autism. Competing Interest Statement The authors have declared no competing interest.