The autism spectrum disorder risk gene NEXMIF over-synchronizes hippocampal CA1 network and alters neuronal coding
Year: 2023
Type: article
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.
Source: Frontiers in Neuroscience
Institution: Boston University
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,295
Awards: CIF: Medium: Discovering Changes in Networks: Fundamental Limits, Efficient Algorithms, and Large-Scale Neuroscience, G2281562814, G3220507079, Study of NEXMIF mosaic expression on neuronal development and connectivity in female mice, G5146764941, Collaborative Research: Dynamic interactions of individual neurons in supporting hippocampal network oscillations during behavior, Convergence: RAISE Integrating machine learning and biological neural networks, Advanced laser scanning confocal microscope for multiple users, Training Program in Quantitative Biology and Physiology, Mechanistic study of the role of autism spectrum disorder risk genes in hippocampal CA1 population dynamics during learning and memory, Graduate Research Fellowship (GRFP), Molecular mechanisms of homeostatic synaptic plasticity, Translational Research in Biomaterials
OpenAlex ID: W4387998418