Open AccessThe voltage-gated Ca2+ channel subunit α2δ-4 regulates locomotor behavior and sensorimotor gating in mice
Author(s) -
Annette Klomp,
Ryotaro Omichi,
Yoh-ichiro Iwasa,
Richard J. Smith,
Yuriy M. Usachev,
Andrew F. Russo,
Nandakumar S. Narayanan,
Amy Lee
Publication year - 2022
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0263197
Subject(s) - gating , protein subunit , voltage gated ion channel , neuroscience , ion channel , biophysics , chemistry , biology , biochemistry , gene , receptor
Voltage-gated Ca 2+ channels are critical for the development and mature function of the nervous system. Variants in the CACNA2D4 gene encoding the α 2 δ-4 auxiliary subunit of these channels are associated with neuropsychiatric and neurodevelopmental disorders. α 2 δ-4 is prominently expressed in the retina and is crucial for vision, but extra-retinal functions of α 2 δ-4 have not been investigated. Here, we sought to fill this gap by analyzing the behavioral phenotypes of α 2 δ-4 knockout (KO) mice. α 2 δ-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 α 2 δ-4 KO mice of both sexes were hyperactive in various assays, only females showed impaired motor coordination in the rotarod assay. α 2 δ-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 α 2 δ-4 in sensorimotor gating and motor function and identify α 2 δ-4 KO mice as a novel model for studying the pathophysiology associated with CACNA2D4 variants.