biostudies-literatureKlomp ANIMH NIH HHSNINDS NIH HHSNational Institutes of Healthe0263197https://www.ebi.ac.uk/biostudies/studies/S-EPMC8967030biostudies-literatureUnknown17(3)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 cooPloS oneThe voltage-gated Ca2+ channel subunit α2δ-4 regulates locomotor behavior and sensorimotor gating in mice.PMC8967030EY026817DC017955NS075599DC012049R01 MH116043NS113189NS115653R01 NS125884R03 NS115653MH116043DC002842R01 NS075599R01 NS113189Usachev YMLee ARusso AFNarayanan NSKlomp ASmith RJIwasa YOmichi RfalseThe 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 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 coo2022-01-01T00:00:00Z20222025-04-26T15:15:43.365Z2025-04-06T14:52:34.249ZS-EPMC89670303535383510.1371/journal.pone.0263197