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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Main Authors: Annette Klomp, Ryotaro Omichi, Yoichiro Iwasa, Richard J Smith, Yuriy M Usachev, Andrew F Russo, Nandakumar S Narayanan, Amy Lee
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-01-01
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.
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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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