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Infant and adult SCA13 mutations differentially affect Purkinje cell excitability, maturation, and viability in vivo.
Elife. 2020 Jul 09; 9E

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.

Authors+Show Affiliations

Department 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.Department 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.Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, United States.Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, United States.Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, United States.Department 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 States.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32644043

Citation

Hsieh, Jui-Yi, et al. "Infant and Adult SCA13 Mutations Differentially Affect Purkinje Cell Excitability, Maturation, and Viability in Vivo." ELife, vol. 9, 2020.
Hsieh JY, Ulrich BN, Issa FA, et al. Infant and adult SCA13 mutations differentially affect Purkinje cell excitability, maturation, and viability in vivo. Elife. 2020;9.
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. https://doi.org/10.7554/eLife.57358
Hsieh JY, et al. Infant and Adult SCA13 Mutations Differentially Affect Purkinje Cell Excitability, Maturation, and Viability in Vivo. Elife. 2020 Jul 9;9 PubMed PMID: 32644043.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Infant and adult SCA13 mutations differentially affect Purkinje cell excitability, maturation, and viability in vivo. AU - Hsieh,Jui-Yi, AU - Ulrich,Brittany N, AU - Issa,Fadi A, AU - Lin,Meng-Chin A, AU - Brown,Brandon, AU - Papazian,Diane M, Y1 - 2020/07/09/ PY - 2020/03/29/received PY - 2020/07/08/accepted PY - 2020/7/10/pubmed PY - 2020/7/10/medline PY - 2020/7/10/entrez KW - Purkinje cell KW - cerebellar development KW - cerebellum KW - degeneration KW - excitability KW - neuroscience KW - spinocerebellar ataxia KW - zebrafish JF - eLife JO - Elife VL - 9 N2 - 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. SN - 2050-084X UR - https://www.unboundmedicine.com/medline/citation/32644043/Infant_and_adult_SCA13_mutations_differentially_affect_Purkinje_cell_excitability,_maturation,_and_viability_in_vivo L2 - https://doi.org/10.7554/eLife.57358 DB - PRIME DP - Unbound Medicine ER -
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