
==== Front
Res Sq
ResearchSquare
Research Square
2693-5015
American Journal Experts

10.21203/rs.3.rs-4925935/v1
10.21203/rs.3.rs-4925935
preprint
1
Article
SCN2A-linked myelination deficits and synaptic plasticity alterations drive auditory processing disorders in ASD
Kim Jun Hee https://orcid.org/0000-0003-0207-8410

Bae Han-Gyu https://orcid.org/0000-0001-7542-552X

Wu Wan-Chen
Nip Kaila
Gould Elizabeth
28 8 2024
rs.3.rs-4925935https://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
https://www.researchsquare.com/article/rs-4925935/v1
nihpp-rs4925935v1.pdf
Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by complex sensory processing deficits. A key unresolved question is how alterations in neural connectivity and communication translate into the behavioral manifestations seen in ASD. Here, we investigate how oligodendrocyte dysfunction alters myelin plasticity and neuronal activity, leading to auditory processing disorder associated with ASD. We focus on the SCN2A gene, an ASD-risk factor, to understand its role in myelination and neural processing within the auditory nervous system. Through transcriptional profiling, we identified alterations in the expression of myelin-associated genes in Scn2a conditional knockout mice, highlighting the cellular consequences engendered by Scn2a deletion in oligodendrocytes. The results reveal a nuanced interplay between oligodendrocytes and axons, where Scn2a deletion causes alterations in the intricate process of myelination. This disruption instigates changes in axonal properties, presynaptic excitability, and synaptic plasticity at the single cell level. Furthermore, oligodendrocyte-specific Scn2a deletion compromises the integrity of neural circuitry within auditory pathways, leading to auditory hypersensitivity. Our findings reveal a novel pathway linking myelin deficits to synaptic activity and sensory abnormalities in ASD.
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