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The autism spectrum disorder risk gene NEXMIF alters hippocampal CA1 cellular and network dynamics

View ORCID ProfileRebecca A. Mount, Mohamed Athif, Margaret O’Connor, Amith Saligrama, Hua-an Tseng, View ORCID ProfileSudiksha Sridhar, Chengqian Zhou, View ORCID ProfileHeng-Ye Man, Xue Han
doi: https://doi.org/10.1101/2022.10.21.513282
Rebecca A. Mount
1Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA
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Mohamed Athif
1Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA
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Margaret O’Connor
2Department of Biology, Boston University, Boston, MA 02215, USA
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Amith Saligrama
1Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA
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Hua-an Tseng
1Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA
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Sudiksha Sridhar
1Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA
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Chengqian Zhou
1Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA
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Heng-Ye Man
2Department of Biology, Boston University, Boston, MA 02215, USA
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  • For correspondence: xuehan@bu.edu hman@bu.edu
Xue Han
1Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA
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  • For correspondence: xuehan@bu.edu hman@bu.edu
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Abstract

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 Statement

The authors have declared no competing interest.

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Posted October 24, 2022.
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The autism spectrum disorder risk gene NEXMIF alters hippocampal CA1 cellular and network dynamics
Rebecca A. Mount, Mohamed Athif, Margaret O’Connor, Amith Saligrama, Hua-an Tseng, Sudiksha Sridhar, Chengqian Zhou, Heng-Ye Man, Xue Han
bioRxiv 2022.10.21.513282; doi: https://doi.org/10.1101/2022.10.21.513282
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The autism spectrum disorder risk gene NEXMIF alters hippocampal CA1 cellular and network dynamics
Rebecca A. Mount, Mohamed Athif, Margaret O’Connor, Amith Saligrama, Hua-an Tseng, Sudiksha Sridhar, Chengqian Zhou, Heng-Ye Man, Xue Han
bioRxiv 2022.10.21.513282; doi: https://doi.org/10.1101/2022.10.21.513282

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