Journal article
The voltage-gated Ca2+ channel subunit α2δ-4 regulates locomotor behavior and sensorimotor gating in mice
PloS one, Vol.17(3), pp.e0263197-e0263197
03/30/2022
DOI: 10.1371/journal.pone.0263197
PMCID: PMC8967030
PMID: 35353835
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.
Details
- Title: Subtitle
- The voltage-gated Ca2+ channel subunit α2δ-4 regulates locomotor behavior and sensorimotor gating in mice
- Creators
- Annette Klomp - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa, United States of AmericaRyotaro Omichi - University of IowaYoichiro Iwasa - University of IowaRichard J Smith - University of IowaYuriy M Usachev - University of IowaAndrew F Russo - Department of Neurology, University of Iowa, Iowa City, Iowa, United States of AmericaNandakumar S Narayanan - University of IowaAmy Lee - Department of Neurology, University of Iowa, Iowa City, Iowa, United States of America
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.17(3), pp.e0263197-e0263197
- DOI
- 10.1371/journal.pone.0263197
- PMID
- 35353835
- PMCID
- PMC8967030
- NLM abbreviation
- PLoS One
- eISSN
- 1932-6203
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: NS115653; DOI: 10.13039/100000002, name: National Institutes of Health, award: EY026817; DOI: 10.13039/100000002, name: National Institutes of Health, award: NS075599; DOI: 10.13039/100000002, name: National Institutes of Health, award: MH116043; DOI: 10.13039/100000002, name: National Institutes of Health, award: NS113189; DOI: 10.13039/100000002, name: National Institutes of Health, award: DC002842; DOI: 10.13039/100000002, name: National Institutes of Health, award: DC012049; DOI: 10.13039/100000002, name: National Institutes of Health, award: DC017955
- Language
- English
- Date published
- 03/30/2022
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center; Anesthesia; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Otolaryngology; Internal Medicine
- Record Identifier
- 9984230416902771
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