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The Cl(-)-channel TMEM16A controls the generation of cochlear Ca(2+) waves and promotes the refinement of auditory brainstem networks

Item Type:Preprint
Title:The Cl(-)-channel TMEM16A controls the generation of cochlear Ca(2+) waves and promotes the refinement of auditory brainstem networks
Creators Name:Maul, A. and Jovanovic, S. and Huebner, A.K. and Strenzke, N. and Moser, T. and Rübsamen, R. and Hübner, C.A.
Abstract:Before hearing onset (postnatal day 12 in mice), inner hair cells (IHC) spontaneously fire action potentials thereby driving pre-sensory activity in the ascending auditory pathway. The rate of IHC action potential bursts is modulated by inner supporting cells (ISC) of Kölliker's organ through the activity of the Ca(2+) activated Cl(-) channel TMEM16A. Here we show that conditional deletion of Tmem16a in mice disrupts the generation of Ca(2+) waves within Kölliker's organ, reduces the burst firing activity and the frequency-selectivity of auditory brainstem neurons in the medial nucleus of the trapezoid body (MNTB), and also impairs the refinement of MNTB projections to the lateral superior olive (LSO). These results reveal the importance of the activity of Kölliker’s organ for the refinement of central auditory connectivity. In addition, our study suggests a mechanism for the generation of Ca(2+) waves, which may also apply to other tissues expressing TMEM16A.
Keywords:TMEM16A, ANO1, Cochlea, Kölliker's Organ, Auditory System, Refinement, Animals, Mice
Source:bioRxiv
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2021.07.05.451099
Date:5 July 2021
Official Publication:https://doi.org/10.1101/2021.07.05.451099

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