The 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 re...
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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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Series: | PLoS ONE |
Online Access: | https://doi.org/10.1371/journal.pone.0263197 |
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author | Annette Klomp Ryotaro Omichi Yoichiro Iwasa Richard J Smith Yuriy M Usachev Andrew F Russo Nandakumar S Narayanan Amy Lee |
author_facet | Annette Klomp Ryotaro Omichi Yoichiro Iwasa Richard J Smith Yuriy M Usachev Andrew F Russo Nandakumar S Narayanan Amy Lee |
author_sort | Annette Klomp |
collection | DOAJ |
description | 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. |
first_indexed | 2024-04-10T16:05:16Z |
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institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-04-10T16:05:16Z |
publishDate | 2022-01-01 |
publisher | Public Library of Science (PLoS) |
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series | PLoS ONE |
spelling | doaj.art-d476844d6e3843fda04f62530a857a902023-02-10T05:31:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01173e026319710.1371/journal.pone.0263197The voltage-gated Ca2+ channel subunit α2δ-4 regulates locomotor behavior and sensorimotor gating in mice.Annette KlompRyotaro OmichiYoichiro IwasaRichard J SmithYuriy M UsachevAndrew F RussoNandakumar S NarayananAmy LeeVoltage-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.https://doi.org/10.1371/journal.pone.0263197 |
spellingShingle | Annette Klomp Ryotaro Omichi Yoichiro Iwasa Richard J Smith Yuriy M Usachev Andrew F Russo Nandakumar S Narayanan Amy Lee The voltage-gated Ca2+ channel subunit α2δ-4 regulates locomotor behavior and sensorimotor gating in mice. PLoS ONE |
title | The voltage-gated Ca2+ channel subunit α2δ-4 regulates locomotor behavior and sensorimotor gating in mice. |
title_full | The voltage-gated Ca2+ channel subunit α2δ-4 regulates locomotor behavior and sensorimotor gating in mice. |
title_fullStr | The voltage-gated Ca2+ channel subunit α2δ-4 regulates locomotor behavior and sensorimotor gating in mice. |
title_full_unstemmed | The voltage-gated Ca2+ channel subunit α2δ-4 regulates locomotor behavior and sensorimotor gating in mice. |
title_short | The voltage-gated Ca2+ channel subunit α2δ-4 regulates locomotor behavior and sensorimotor gating in mice. |
title_sort | voltage gated ca2 channel subunit α2δ 4 regulates locomotor behavior and sensorimotor gating in mice |
url | https://doi.org/10.1371/journal.pone.0263197 |
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