The Cl--channel TMEM16A is involved in the generation of cochlear Ca2+ waves and promotes the refinement of auditory brainstem networks in mice
- Max Delbrück Center for Molecular Medicine, Germany
- University Hospital Jena, Germany
- University of Göttingen, Germany
- University of Leipzig, Germany
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 Ca2+ activated Cl- channel TMEM16A (ANO1). Here we show that conditional deletion of Ano1 (Tmem16a) in mice disrupts Ca2+ 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 functional 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 involvement of TMEM16A in the propagation of Ca2+ waves, which may also apply to other tissues expressing TMEM16A.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided and did not change for the revised manuscript.
Article and author information
Author details
Christian A Hübner
Funding
Deutsche Forschungsgemeinschaft (HU 800/10-1)
- Christian A Hübner
Deutsche Forschungsgemeinschaft (priority program 1608)
- Nicola Strenzke
- Tobias Moser
- Rudolf Rübsamen
Bundesministerium für Bildung und Forschung (01EW1706)
- Christian A Hübner
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to our local authorities (license numbers: 33.9-42502-04-11/0439; TVV 06/09 and TLV UKJ-17-006).
Copyright
© 2022, Maul et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The Cl--channel TMEM16A is involved in the generation of cochlear Ca2+ waves and promotes the refinement of auditory brainstem networks in mice
eLife 11:e72251.
https://doi.org/10.7554/eLife.72251
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