RT Journal Article SR Electronic T1 The autism spectrum disorder risk gene NEXMIF alters hippocampal CA1 cellular and network dynamics JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.10.21.513282 DO 10.1101/2022.10.21.513282 A1 Rebecca A. Mount A1 Mohamed Athif A1 Margaret O’Connor A1 Amith Saligrama A1 Hua-an Tseng A1 Sudiksha Sridhar A1 Chengqian Zhou A1 Heng-Ye Man A1 Xue Han YR 2022 UL http://biorxiv.org/content/early/2022/10/24/2022.10.21.513282.abstract AB Perturbations in autism spectrum disorder (ASD) risk genes disrupt neural circuit dynamics and ultimately lead to behavioral abnormalities. To understand how ASD-implicated genes influence network computation during behavior, we performed in vivo calcium imaging from hundreds of individual hippocampal CA1 neurons simultaneously in freely locomoting mice with total knockout of NEXMIF. NEXMIF is an ASD risk gene most highly expressed in the hippocampus, and NEXMIF knockout in mice creates a range of behavioral deficits, including impaired hippocampal-dependent memory. We found that NEXMIF knockout does not alter the overall excitability of individual neurons but exaggerates movement-mediated neuronal responses. At the network level, NEXMIF knockout creates over-synchronization of the CA1 circuit, quantified by pairwise correlation and network closeness centrality. These neuronal effects observed upon NEXMIF knockout highlight the network consequences of perturbations in ASD-implicated genes, which have broad implications for cognitive performance and other ASD-related behavioral disruptions.Competing Interest StatementThe authors have declared no competing interest.