Infant and adult SCA13 mutations differentially affect Purkinje cell excitability, maturation, and viability in vivo
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...
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eLife Sciences Publications Ltd
2020-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/57358 |
| _version_ | 1811236155274821632 |
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| author | Jui-Yi Hsieh Brittany N Ulrich Fadi A Issa Meng-chin A Lin Brandon Brown Diane M Papazian |
| author_facet | Jui-Yi Hsieh Brittany N Ulrich Fadi A Issa Meng-chin A Lin Brandon Brown Diane M Papazian |
| author_sort | Jui-Yi Hsieh |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T12:05:10Z |
| format | Article |
| id | doaj.art-deb44c8fd70d4b44b78d1c6a0a76f22a |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:05:10Z |
| publishDate | 2020-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-deb44c8fd70d4b44b78d1c6a0a76f22a2022-12-22T03:33:45ZengeLife Sciences Publications LtdeLife2050-084X2020-07-01910.7554/eLife.57358Infant and adult SCA13 mutations differentially affect Purkinje cell excitability, maturation, and viability in vivoJui-Yi Hsieh0Brittany N Ulrich1Fadi A Issa2https://orcid.org/0000-0001-5234-5850Meng-chin A Lin3Brandon Brown4Diane M Papazian5https://orcid.org/0000-0001-8194-5740Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, United States; Interdepartmental PhD Program in Molecular, Cellular, and Integrative Physiology, David Geffen School of Medicine at UCLA, Los Angeles, United StatesDepartment of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, United States; Interdepartmental PhD Program in Molecular, Cellular, and Integrative Physiology, David Geffen School of Medicine at UCLA, Los Angeles, United StatesDepartment of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, United StatesDepartment of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, United StatesDepartment of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, United StatesDepartment of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, United States; Interdepartmental PhD Program in Molecular, Cellular, and Integrative Physiology, David Geffen School of Medicine at UCLA, Los Angeles, United States; Brain Research Institute, UCLA, Los Angeles, United States; Molecular Biology Institute, UCLA, Los Angeles, United StatesMutations 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.https://elifesciences.org/articles/57358cerebellumspinocerebellar ataxiaPurkinje cellexcitabilitycerebellar developmentdegeneration |
| spellingShingle | Jui-Yi Hsieh Brittany N Ulrich Fadi A Issa Meng-chin A Lin Brandon Brown Diane M Papazian Infant and adult SCA13 mutations differentially affect Purkinje cell excitability, maturation, and viability in vivo eLife cerebellum spinocerebellar ataxia Purkinje cell excitability cerebellar development degeneration |
| title | Infant and adult SCA13 mutations differentially affect Purkinje cell excitability, maturation, and viability in vivo |
| title_full | Infant and adult SCA13 mutations differentially affect Purkinje cell excitability, maturation, and viability in vivo |
| title_fullStr | Infant and adult SCA13 mutations differentially affect Purkinje cell excitability, maturation, and viability in vivo |
| title_full_unstemmed | Infant and adult SCA13 mutations differentially affect Purkinje cell excitability, maturation, and viability in vivo |
| title_short | Infant and adult SCA13 mutations differentially affect Purkinje cell excitability, maturation, and viability in vivo |
| title_sort | infant and adult sca13 mutations differentially affect purkinje cell excitability maturation and viability in vivo |
| topic | cerebellum spinocerebellar ataxia Purkinje cell excitability cerebellar development degeneration |
| url | https://elifesciences.org/articles/57358 |
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