PT  - JOURNAL ARTICLE
AU  - Rebecca A. Mount
AU  - Mohamed Athif
AU  - Margaret O’Connor
AU  - Amith Saligrama
AU  - Hua-an Tseng
AU  - Sudiksha Sridhar
AU  - Chengqian Zhou
AU  - Heng-Ye Man
AU  - Xue Han
TI  - The autism spectrum disorder risk gene <em>NEXMIF</em> alters hippocampal CA1 cellular and network dynamics
AID  - 10.1101/2022.10.21.513282
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.10.21.513282
4099  - http://biorxiv.org/content/early/2022/10/24/2022.10.21.513282.short
4100  - http://biorxiv.org/content/early/2022/10/24/2022.10.21.513282.full
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.