1. Neuroscience

Infant and adult SCA13 mutations differentially affect Purkinje cell excitability, maturation, and viability in vivo

  1. Jui-Yi Hsieh
  2. Brittany N Ulrich
  3. Fadi A Issa
  4. Meng-chin A Lin
  5. Brandon Brown
  6. Diane M Papazian  Is a corresponding author
  1. Geffen School of Medicine at UCLA, United States
  2. East Carolina University, United States
https://doi.org/10.7554/eLife.57358
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Cite this article
  1. Jui-Yi Hsieh
  2. Brittany N Ulrich
  3. Fadi A Issa
  4. Meng-chin A Lin
  5. Brandon Brown
  6. Diane M Papazian
(2020)
Infant and adult SCA13 mutations differentially affect Purkinje cell excitability, maturation, and viability in vivo
eLife 9:e57358.
https://doi.org/10.7554/eLife.57358
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Abstract

Mutations in KCNC3, which encodes the Kv3.3 K+ channel, cause spinocerebellar ataxia 13 (SCA13). SCA13 exists in distinct forms with onset in infancy or adulthood. Using zebrafish, we tested the hypothesis that infant- and adult-onset mutations differentially affect the excitability and viability of Purkinje cells in vivo during cerebellar development. An infant-onset mutation dramatically and transiently increased Purkinje cell excitability, stunted process extension, impaired dendritic branching and synaptogenesis, and caused rapid cell death during cerebellar development. Reducing excitability increased early Purkinje cell survival. In contrast, an adult-onset mutation did not significantly alter basal tonic firing in Purkinje cells, but reduced excitability during evoked high frequency spiking. Purkinje cells expressing the adult-onset mutation matured normally and did not degenerate during cerebellar development. Our results suggest that differential changes in the excitability of cerebellar neurons contribute to the distinct ages of onset and timing of cerebellar degeneration in infant- and adult-onset SCA13.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Jui-Yi Hsieh

    Physiology, Geffen School of Medicine at UCLA, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Brittany N Ulrich

    Physiology, Geffen School of Medicine at UCLA, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Fadi A Issa

    Biology, East Carolina University, Greenville, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5234-5850

  4. Meng-chin A Lin

    Physiology, Geffen School of Medicine at UCLA, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Brandon Brown

    Physiology, Geffen School of Medicine at UCLA, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Diane M Papazian

    Physiology, Geffen School of Medicine at UCLA, Los Angeles, United States
    For correspondence
    papazian@mednet.ucla.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8194-5740

Funding

National Institutes of Health (R01 NS058500)

  • Diane M Papazian

National Ataxia Foundation (NA)

  • Fadi A Issa

UCLA Stein Oppenheimer Seed Grant (NA)

  • Diane M Papazian

UCLA Jennifer Buchwald Graduate Fellowship (NA)

  • Jui-Yi Hsieh
  • Brittany N Ulrich

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols of the University of California, Los Angeles. The protocols were approved by the Chancellor's Animal Research Committee (#2005-176 and #1991-329). All surgery was performed under MS-222 anesthesia, and every effort was made to minimize suffering.

Copyright

© 2020, Hsieh et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Jui-Yi Hsieh
  2. Brittany N Ulrich
  3. Fadi A Issa
  4. Meng-chin A Lin
  5. Brandon Brown
  6. Diane M Papazian
(2020)
Infant and adult SCA13 mutations differentially affect Purkinje cell excitability, maturation, and viability in vivo
eLife 9:e57358.
https://doi.org/10.7554/eLife.57358

Share this article

https://doi.org/10.7554/eLife.57358

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