{"doi":"10.1371/journal.pone.0263197","title":"The voltage-gated Ca2+ channel subunit α2δ-4 regulates locomotor behavior and sensorimotor gating in mice","abstract":"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.","journal":"PLoS ONE","year":2022,"id":263998,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9515,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":457586,"name":"Ryotaro Omichi","orcid":"0000-0001-5441-9796","position":1,"is_corresponding":false},{"id":921501,"name":"Yoh-ichiro Iwasa","orcid":"0000-0001-8989-9021","position":2,"is_corresponding":false},{"id":291758,"name":"Richard J. Smith","orcid":"0000-0003-1201-6731","position":3,"is_corresponding":false},{"id":256366,"name":"Yuriy M. Usachev","orcid":"0000-0002-6948-4627","position":4,"is_corresponding":false},{"id":273685,"name":"Andrew F. Russo","orcid":"0000-0002-8156-5649","position":5,"is_corresponding":false},{"id":98533,"name":"Nandakumar S. Narayanan","orcid":"0000-0002-0427-0003","position":6,"is_corresponding":false},{"id":607694,"name":"Amy Lee","orcid":"0000-0001-8021-0443","position":7,"is_corresponding":false},{"id":920925,"name":"Annette Klomp","orcid":"0000-0002-0287-6925","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T00:26:37.567338Z","pmid":"35353835","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}