Parallel anterior cingulate cortex pathways underlie dissociable social and attentional outputs.

Abstract

The neural mechanisms coordinating social behavior and attentional control are often disrupted together in individuals with neuropsychiatric disorders such as autism spectrum disorder (ASD); however, how distinct circuits within a shared brain region separately regulate these functions remains unclear. Here, we identified two functionally distinct subpopulations of glutamatergic neurons in the anterior cingulate cortex (ACC) that project to different downstream targets: the zona incerta (ZI) and the limbic sector of the thalamic reticular nucleus (lTRN). These two ACC subpopulations differentially mediate social interaction and attentional allocation. Deficits in both behaviors were observed in <i>Shank3b</i> mutant ASD model mice. Optogenetic activation of the ACC→ZI circuit rescued social impairments, whereas activation of the ACC→lTRN pathway restored attentional performance. Our findings reveal dissociable ACC subpopulations and their downstream circuits for social and attentional behaviors, providing circuit-level insights that may inform future research on modulating related symptoms in patients with psychiatric disorders.