PUBLICATION
Infant and adult SCA13 mutations differentially affect Purkinje cell excitability, maturation, and viability in vivo
- Authors
- Hsieh, J.Y., Ulrich, B.N., Issa, F.A., Lin, M.A., Brown, B., Papazian, D.M.
- ID
- ZDB-PUB-200710-22
- Date
- 2020
- Source
- eLIFE 9: (Journal)
- Registered Authors
- Lin, Meng-Chin, Papazian, Diane M.
- Keywords
- neuroscience, zebrafish
- MeSH Terms
-
- Age Factors
- Animals
- Cell Survival/genetics*
- Cerebellum/growth & development
- Disease Models, Animal
- Mutation*
- Purkinje Cells/physiology*
- Shaw Potassium Channels/genetics*
- Spinocerebellar Ataxias/congenital*
- Spinocerebellar Ataxias/genetics
- Zebrafish
- Zebrafish Proteins/genetics*
- PubMed
- 32644043 Full text @ Elife
Citation
Hsieh, J.Y., Ulrich, B.N., Issa, F.A., Lin, M.A., Brown, B., Papazian, D.M. (2020) Infant and adult SCA13 mutations differentially affect Purkinje cell excitability, maturation, and viability in vivo. eLIFE. 9:.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping