The neural basis of abnormal social behavior in autism spectrum disorders (ASD) remains incompletely understood. As social behavior involves complex interactions between multiple brain regions, a comprehensive understanding of disease mechanisms is best approached via brain-wide analyses. We used two complementary but independent brain-wide mapping approaches, mouse resting-state fMRI and c-Fos-iDISCO imaging, to construct brain-wide activity maps of the Cntnap2 knockout mouse model of ASD. We found lower activity and disrupted functional coupling across social brain regions of these mice. Oxytocin administration, which rescues social deficits in these mice, strongly stimulated these areas and normalized functional connectivity. Notably, DREADD-triggered release of endogenous oxytocin strongly stimulated reward areas including the nucleus accumbens, where oxytocin receptor activation also rescued lowered excitatory synaptic drive. Our findings establish circuit- and systems-level mechanisms of social deficits in Cntnap2 knockout mice, and reveal site-specific actions of oxytocin promoting the coordinated activity of social brain regions.
This seminar will be held online via Zoom.