Inferior Olivary TMEM16B Mediates Cerebellar Motor Learning.

Published

Journal Article

Ca2+-activated ion channels shape membrane excitability and Ca2+ dynamics in response to cytoplasmic Ca2+ elevation. Compared to the Ca2+-activated K+ channels, known as BK and SK channels, the physiological importance of Ca2+-activated Cl- channels (CaCCs) in neurons has been largely overlooked. Here we report that CaCCs coexist with BK and SK channels in inferior olivary (IO) neurons that send climbing fibers to innervate cerebellar Purkinje cells for the control of motor learning and timing. Ca2+ influx through the dendritic high-threshold voltage-gated Ca2+ channels activates CaCCs, which contribute to membrane repolarization of IO neurons. Loss of TMEM16B expression resulted in the absence of CaCCs in IO neurons, leading to markedly diminished action potential firing of IO neurons in TMEM16B knockout mice. Moreover, these mutant mice exhibited severe cerebellar motor learning deficits. Our findings thus advance the understanding of the neurophysiology of CaCCs and the ionic basis of IO neuron excitability.

Full Text

Duke Authors

Cited Authors

  • Zhang, Y; Zhang, Z; Xiao, S; Tien, J; Le, S; Le, T; Jan, LY; Yang, H

Published Date

  • August 30, 2017

Published In

Volume / Issue

  • 95 / 5

Start / End Page

  • 1103 - 1111.e4

PubMed ID

  • 28858616

Pubmed Central ID

  • 28858616

Electronic International Standard Serial Number (EISSN)

  • 1097-4199

Digital Object Identifier (DOI)

  • 10.1016/j.neuron.2017.08.010

Language

  • eng

Conference Location

  • United States