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 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.
['Hsieh|Jui-Yi|JY|', 'Ulrich|Brittany N|BN|', 'Issa|Fadi A|FA|0000-0001-5234-5850', 'Lin|Meng-Chin A|MA|', 'Brown|Brandon|B|', 'Papazian|Diane M|DM|0000-0001-8194-5740']
D000367:Age Factors D000818:Animals D002470:Cell Survival D002531:Cerebellum D004195:Disease Models, Animal D009154:Mutation D011689:Purkinje Cells D051670:Shaw Potassium Channels D020754:Spinocerebellar Ataxias D015027:Zebrafish D029961:Zebrafish Proteins
Purkinje cell excitability spinocerebellar ataxia zebrafish cerebellar development degeneration cerebellum neuroscience