Entrainment of prefrontal theta synchrony increases interbrain coupling and enhances social interaction in mouse models of autism

Social interaction requires the integration of information about self, other, and shared context. One of the proposed mechanisms supporting this coordination is interbrain synchrony – correlated neural activity between interacting individuals – yet its role in shaping social behavior remains unresolved. Here, we show that theta band synchrony in the medial prefrontal cortex (mPFC) is closely linked to social interaction in mice and often precedes its onset. In male Shank2 mutant mice, a genetic model of social dysfunction, mPFC interbrain synchrony was diminished, along with a reduced population of mPFC neurons encoding multiple dimensions of social information. Optogenetic entrainment of theta synchrony was accompanied by increased interbrain coupling and social interaction in male Shank2-/- and Tbr1+/K228E mutant mice, two well-established genetic models of autism spectrum disorder (ASD). These findings identify prefrontal theta synchrony as a neural substrate that supports social behavior and provide a framework for understanding how coordinated neural activity across brains contributes to social interaction. Brain rhythms of interacting mice become synchronized, but this coordination is reduced in mouse models of autism. Here the authors show that theta-frequency stimulation is accompanied by increased interbrain synchrony and social interaction.