Distinct functions of parvalbumin and somatostatin interneurons in the anterior cingulate cortex result in heterogeneity of social interaction impairments

Abstract

The anterior cingulate cortex (ACC) serves as a core region in social networks, and impairments in this area have been identified in autism spectrum disorders. Our prior research demonstrated that deficits in pyramidal neurons in ACC adversely impacted mouse social interaction. The preservation of functional output in the ACC by pyramidal neurons relies on the dynamic regulation by the different types of interneurons. However, the precise regulatory roles of distinct interneurons within the ACC in shaping social interaction have hitherto remained largely enigmatic. In this study, we elucidated the involvement of parvalbumin (PV) and somatostatin (SST) interneurons within the ACC in modulating social interaction behavior. Specifically, we ascertain that PV interneurons play a more prominent role in initiating sociability, whereas SST interneurons uniquely influence social preference. Notably, the downregulation of the autism high-risk gene Kcnh7 is identified in both PV and SST interneurons within the Shank3 knockout (KO) autistic mouse model. Further, the selective KO of Kcnh7 in PV- or SST-positive neurons contributes to disruptions in sociability and social preference, respectively. The divergent modulation of social interaction by PV and SST interneurons in the ACC is attributed to the distinct input received by these neuronal subtypes. Our findings offer nuanced insights into the multifaceted roles of PV and SST neurons within the ACC in the context of social interaction, contributing to a comprehensive understanding of the neurobiological underpinnings of social behavior disorders in autism. The delineation of these mechanisms is imperative for advancing our comprehension of the etiological basis of autism, thereby paving the way for novel avenues of research aimed at addressing the heterogeneous phenotypes associated with social interaction dysfunction in cortical interneurons.