biostudies-literatureChoe KYNIMH NIH HHSNINDS NIH HHSCIHR795-808.e6https://www.ebi.ac.uk/biostudies/studies/S-EPMC8944915biostudies-literatureUnknown110(5)The neural basis of abnormal social behavior in autism spectrum disorders (ASDs) remains incompletely understood. Here we used two complementary but independent brain-wide mapping approaches, mouse resting-state fMRI and c-Fos-iDISCO+ imaging, to construct brain-wide activity and connectivity maps of the Cntnap2 knockout (KO) mouse model of ASD. At the macroscale level, we detected reduced functional coupling across social brain regions despite general patterns of hyperconnectivity across major brain structures. Oxytocin administration, which rescues social deficits in KO mice, strongly stimulated many brain areas and normalized connectivity patterns. Notably, chemogenetically triggered release of endogenous oxytocin strongly stimulated the nucleus accumbens (NAc), a forebrain nucleus implNeuronOxytocin normalizes altered circuit connectivity for social rescue of the Cntnap2 knockout mouse.PMC8944915R01 MH100027K01 MH116264R01 NS091222K99 MH115143Bethlehem RAILi YPenagarikano ODong HSalman EChoe KYSafrin MDeNardo LAHarris NGGolshani PGeschwind DHGrinevich VfalseOxytocin normalizes altered circuit connectivity for social rescue of the Cntnap2 knockout mouse.The neural basis of abnormal social behavior in autism spectrum disorders (ASDs) remains incompletely understood. Here we used two complementary but independent brain-wide mapping approaches, mouse resting-state fMRI and c-Fos-iDISCO+ imaging, to construct brain-wide activity and connectivity maps of the Cntnap2 knockout (KO) mouse model of ASD. At the macroscale level, we detected reduced functional coupling across social brain regions despite general patterns of hyperconnectivity across major brain structures. Oxytocin administration, which rescues social deficits in KO mice, strongly stimulated many brain areas and normalized connectivity patterns. Notably, chemogenetically triggered release of endogenous oxytocin strongly stimulated the nucleus accumbens (NAc), a forebrain nucleus impl2022-01-01T00:00:00Z2022 Mar2025-04-04T08:07:48.139Z2025-04-04T08:07:48.139ZS-EPMC89449153493294110.1016/j.neuron.2021.11.031