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

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 hippocamp...

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Published inbioRxiv
Main Authors Mount, Rebecca A, Athif, Mohamed, O'connor, Margaret, Saligrama, Amith, Hua-An Tseng, Sudiksha Sridhar, Zhou, Chengqian, Man, Hengye, Han, Xue
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 24.10.2022
Subjects
Autism
Calcium imaging
Cognitive ability
Excitability
Genes
Hippocampus
Synchronization
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Summary: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.
DOI:10.1101/2022.10.21.513282