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Article Dans Une Revue Neuron Année : 2024

Impaired cerebellar plasticity hypersensitizes sensory reflexes in SCN2A-associated ASD

Chenyu Wang
  • Fonction : Auteur
Kimberly D Derderian
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Elizabeth Hamada
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Xujia Zhou
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Andrew D Nelson
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Henry Kyoung
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Nadav Ahituv
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Kevin J Bender
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Résumé

Children diagnosed with autism spectrum disorder (ASD) commonly present with sensory hypersensitivity, or abnormally strong reactions to sensory stimuli. Such hypersensitivity can be overwhelming, causing high levels of distress that contribute markedly to the negative aspects of the disorder. Here, we identify the mechanisms that underlie hypersensitivity in a sensorimotor reflex found to be altered in humans and in mice with loss-of-function in the ASD risk-factor gene SCN2A. The cerebellum-dependent vestibulo-ocular reflex (VOR), which helps maintain one's gaze during movement, was hypersensitized due to deficits in cerebellar synaptic plasticity. Heterozygous loss of SCN2A-encoded Na V 1.2 sodium channels in granule cells impaired high-frequency transmission to Purkinje cells and long-term potentiation, a form of synaptic plasticity important for modulating VOR gain. VOR plasticity could be rescued in adolescent mice via a CRISPR-activator approach that increases Scn2a expression, highlighting how evaluation of simple reflexes can be used as quantitative readout of therapeutic interventions.
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Dates et versions

hal-04210602 , version 1 (18-09-2023)

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Paternité - Pas d'utilisation commerciale - Pas de modification

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Citer

Chenyu Wang, Kimberly D Derderian, Elizabeth Hamada, Xujia Zhou, Andrew D Nelson, et al.. Impaired cerebellar plasticity hypersensitizes sensory reflexes in SCN2A-associated ASD: cerebellar plasticity in SCN2A-associated ASD. Neuron, In press, pp.S0896-6273(24)00055-2. ⟨10.1016/j.neuron.2024.01.029⟩. ⟨hal-04210602⟩
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