RT Journal Article
SR Electronic
T1 The voltage-gated Ca<sub>v</sub> Ca<sup>2+</sup> channel subunit α<sub>2</sub>δ-4 is required for locomotor behavior and sensorimotor gating in mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.17.476669
DO 10.1101/2022.01.17.476669
A1 Annette Klomp
A1 Ryotaro Omichi
A1 Yoichiro Iwasa
A1 Richard J. Smith
A1 Yuriy M. Usachev
A1 Andrew F. Russo
A1 Nandakumar Narayanan
A1 Amy Lee
YR 2022
UL http://biorxiv.org/content/early/2022/01/17/2022.01.17.476669.abstract
AB Voltage-gated Cav 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 learning/coordination in the rotarod assay. Female but not male 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 cognitive and motor function and identify α2δ-4 KO mice as a novel model for studying the pathophysiology associated with CACNA2D4 variants.Competing Interest StatementThe authors have declared no competing interest.