| First Author | Mount RA | Year | 2023 |
| Journal | Front Neurosci | Volume | 17 |
| Pages | 1277501 | PubMed ID | 37965217 |
| Mgi Jnum | J:342635 | Mgi Id | MGI:7549707 |
| Doi | 10.3389/fnins.2023.1277501 | Citation | Mount RA, et al. (2023) The autism spectrum disorder risk gene NEXMIF over-synchronizes hippocampal CA1 network and alters neuronal coding. Front Neurosci 17:1277501 |
| abstractText | Mutations in autism spectrum disorder (ASD) risk genes disrupt neural network dynamics that ultimately lead to abnormal behavior. To understand how ASD-risk genes influence neural circuit computation during behavior, we analyzed the hippocampal network by performing large-scale cellular calcium imaging from hundreds of individual CA1 neurons simultaneously in transgenic mice with total knockout of the X-linked ASD-risk gene NEXMIF (neurite extension and migration factor). As NEXMIF knockout in mice led to profound learning and memory deficits, we examined the CA1 network during voluntary locomotion, a fundamental component of spatial memory. We found that NEXMIF knockout does not alter the overall excitability of individual neurons but exaggerates movement-related neuronal responses. To quantify network functional connectivity changes, we applied closeness centrality analysis from graph theory to our large-scale calcium imaging datasets, in addition to using the conventional pairwise correlation analysis. Closeness centrality analysis considers both the number of connections and the connection strength between neurons within a network. We found that in wild-type mice the CA1 network desynchronizes during locomotion, consistent with increased network information coding during active behavior. Upon NEXMIF knockout, CA1 network is over-synchronized regardless of behavioral state and fails to desynchronize during locomotion, highlighting how perturbations in ASD-implicated genes create abnormal network synchronization that could contribute to ASD-related behaviors. |
