Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

The voltage-gated Cav Ca2+ channel subunit α2δ-4 is required for locomotor behavior and sensorimotor gating in mice

Annette Klomp, View ORCID ProfileRyotaro Omichi, Yoichiro Iwasa, Richard J. Smith, Yuriy M. Usachev, View ORCID ProfileAndrew F. Russo, Nandakumar Narayanan, View ORCID ProfileAmy Lee
doi: https://doi.org/10.1101/2022.01.17.476669
Annette Klomp
1Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, Iowa, 52242
2Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa, 52242
3Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa, 52242
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ryotaro Omichi
4Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, Iowa, 52242
5Iowa Institute of Human Genetics, University of Iowa, Iowa City, Iowa, 52242
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ryotaro Omichi
Yoichiro Iwasa
4Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, Iowa, 52242
5Iowa Institute of Human Genetics, University of Iowa, Iowa City, Iowa, 52242
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard J. Smith
2Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa, 52242
3Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa, 52242
4Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, Iowa, 52242
5Iowa Institute of Human Genetics, University of Iowa, Iowa City, Iowa, 52242
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yuriy M. Usachev
2Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa, 52242
6Department of Neuroscience and Pharmacology, University of Iowa, Iowa City, Iowa, 52242
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew F. Russo
2Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa, 52242
3Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa, 52242
7Department of Neurology, University of Iowa, Iowa City, Iowa, 52242
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Andrew F. Russo
Nandakumar Narayanan
2Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa, 52242
7Department of Neurology, University of Iowa, Iowa City, Iowa, 52242
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Amy Lee
2Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa, 52242
3Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa, 52242
4Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, Iowa, 52242
7Department of Neurology, University of Iowa, Iowa City, Iowa, 52242
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Amy Lee
  • For correspondence: amy.lee1@austin.utexas.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Voltage-gated Cav 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 learning/coordination in the rotarod assay. Female but not male 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 cognitive and motor function and identify α2δ-4 KO mice as a novel model for studying the pathophysiology associated with CACNA2D4 variants.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted January 17, 2022.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
The voltage-gated Cav Ca2+ channel subunit α2δ-4 is required for locomotor behavior and sensorimotor gating in mice
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
The voltage-gated Cav Ca2+ channel subunit α2δ-4 is required for locomotor behavior and sensorimotor gating in mice
Annette Klomp, Ryotaro Omichi, Yoichiro Iwasa, Richard J. Smith, Yuriy M. Usachev, Andrew F. Russo, Nandakumar Narayanan, Amy Lee
bioRxiv 2022.01.17.476669; doi: https://doi.org/10.1101/2022.01.17.476669
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
The voltage-gated Cav Ca2+ channel subunit α2δ-4 is required for locomotor behavior and sensorimotor gating in mice
Annette Klomp, Ryotaro Omichi, Yoichiro Iwasa, Richard J. Smith, Yuriy M. Usachev, Andrew F. Russo, Nandakumar Narayanan, Amy Lee
bioRxiv 2022.01.17.476669; doi: https://doi.org/10.1101/2022.01.17.476669

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (3580)
  • Biochemistry (7534)
  • Bioengineering (5488)
  • Bioinformatics (20709)
  • Biophysics (10267)
  • Cancer Biology (7942)
  • Cell Biology (11597)
  • Clinical Trials (138)
  • Developmental Biology (6576)
  • Ecology (10151)
  • Epidemiology (2065)
  • Evolutionary Biology (13565)
  • Genetics (9504)
  • Genomics (12801)
  • Immunology (7891)
  • Microbiology (19472)
  • Molecular Biology (7624)
  • Neuroscience (41939)
  • Paleontology (307)
  • Pathology (1253)
  • Pharmacology and Toxicology (2182)
  • Physiology (3254)
  • Plant Biology (7017)
  • Scientific Communication and Education (1291)
  • Synthetic Biology (1944)
  • Systems Biology (5412)
  • Zoology (1109)