The voltage-gated Ca2+ channel subunit α2δ-4 regulates locomotor behavior and sensorimotor gating in mice

Voltage-gated Ca2+ channels are critical for the development and mature function of the nervous system. Variants in the CACNA2D4 gene encoding the α2δ-4 auxiliary subunit of these channels are associated with neuropsychiatric and neurodevelopmental disorders. α2δ-4 is prominently expressed in the re...

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Bibliographic Details
Published in:PloS one 2022, Vol.17 (3), p.e0263197-e0263197
Main Authors: Klomp, Annette, Omichi, Ryotaro, Iwasa, Yoichiro, Smith, Richard J, Usachev, Yuriy M, Russo, Andrew F, Narayanan, Nandakumar S, Lee, Amy
Format: Article
Language:English
Subjects:
Animals
Biology and Life Sciences
Biophysics
Brain stem
Calcium - metabolism
Calcium channels
Calcium channels (voltage-gated)
Calcium Channels, L-Type - genetics
Calcium ions
Channel gating
Channels
Computer and Information Sciences
Ears & hearing
Engineering and Technology
Female
Females
Genes
Male
Medicine and Health Sciences
Mental disorders
Mice
Mice, Knockout
Nervous system
Neurodevelopmental disorders
Neurology
Neurosciences
Otolaryngology
Phenotypes
Photoreceptors
Physiology
Prepulse Inhibition
Research and Analysis Methods
Retina
Sensorimotor gating
Social Sciences
Surgery
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Summary:Voltage-gated Ca2+ channels are critical for the development and mature function of the nervous system. Variants in the CACNA2D4 gene encoding the α2δ-4 auxiliary subunit of these channels are associated with neuropsychiatric and neurodevelopmental disorders. α2δ-4 is prominently expressed in the retina and is crucial for vision, but extra-retinal functions of α2δ-4 have not been investigated. Here, we sought to fill this gap by analyzing the behavioral phenotypes of α2δ-4 knockout (KO) mice. α2δ-4 KO mice (both males and females) exhibited significant impairments in prepulse inhibition that were unlikely to result from the modestly elevated auditory brainstem response thresholds. Whereas α2δ-4 KO mice of both sexes were hyperactive in various assays, only females showed impaired motor coordination in the rotarod assay. α2δ-4 KO mice exhibited anxiolytic and anti-depressive behaviors in the elevated plus maze and tail suspension tests, respectively. Our results reveal an unexpected role for α2δ-4 in sensorimotor gating and motor function and identify α2δ-4 KO mice as a novel model for studying the pathophysiology associated with CACNA2D4 variants.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0263197