He, Yongxiang;
Li, Jiong;
Zheng, Wei;
Liu, Junhong;
Dong, Zhaojun;
Yang, Lu;
Tang, Shuting;
... Xiao, Lin; + view all
(2025)
Hypomyelination in autism-associated neuroligin-3 mutant mice impairs parvalbumin interneuron excitability, gamma oscillations, and sensory discrimination.
Nature Communications
, 16
, Article 6382. 10.1038/s41467-025-61455-0.
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Hypomyelination in autism-associated neuroligin-3 mutant mice impairs parvalbumin interneuron excitability, gamma oscillations, and sensory discrimination.pdf - Published Version Download (12MB) | Preview |
Abstract
Whether and how myelin plasticity, an emerging new form of brain plasticity, is involved in autism spectrum disorder (ASD) remains unknown. Here, we identify deficits in oligodendrocyte (OL) generation and myelination in the barrel cortex (BC) of the male NL3-R451C-KI mouse model of ASD. These mice also show impaired texture recognition, disrupted gamma neuronal oscillations, and reduced excitability and myelination level in the BC-PV interneuron. These abnormalities can be rescued by a promyelinating strategy and are recapitulated by genetic blockade of myelination in Myrf-cKO mice. Furthermore, OL progenitor-specific conditional NL3 knockout mice show similar deficits in BC-PV interneuron myelination and excitability, as well as neuronal oscillation and texture recognition, closely resembling the NL3-R451C-KI phenotype. Collectively, these results demonstrate that NL3 mutations commonly cause hypomyelination and reduced excitability in BC-PV interneurons, disrupting neuronal oscillation and contributing to ASD-like sensory dysfunction. Our finding reveals a mechanism underlying ASD and highlights OLs/myelin as potential therapeutic targets for ASD.
| Type: | Article |
|---|---|
| Title: | Hypomyelination in autism-associated neuroligin-3 mutant mice impairs parvalbumin interneuron excitability, gamma oscillations, and sensory discrimination |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-025-61455-0 |
| Publisher version: | https://doi.org/10.1038/s41467-025-61455-0 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10211136 |
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