The Cl--channel TMEM16A is involved in the generation of cochlear Ca2+ waves and promotes the refinement of auditory brainstem networks in mice

  1. Alena Maul
  2. Antje Kathrin Huebner
  3. Nicola Strenzke
  4. Tobias Moser
  5. Rudolf Rübsamen
  6. Saša Jovanovic
  7. Christian A Hübner  Is a corresponding author
  1. Max Delbrück Center for Molecular Medicine, Germany
  2. University Hospital Jena, Germany
  3. University of Göttingen, Germany
  4. 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

  1. Alena Maul

    Neuroscience Department, Max Delbrück Center for Molecular Medicine, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Antje Kathrin Huebner

    Institute of Human Genetics, University Hospital Jena, Jena, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Nicola Strenzke

    Institute for Auditory Neuroscience, Department of Otolaryngology, University of Göttingen, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1673-1046
  4. Tobias Moser

    Institute for Auditory Neuroscience, Department of Otolaryngology, University of Göttingen, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7145-0533
  5. Rudolf Rübsamen

    Faculty of Bioscience, Pharmacy and Psychology, University of Leipzig, Leipzig, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Saša Jovanovic

    Faculty of Bioscience, Pharmacy and Psychology, University of Leipzig, Leipzig, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Christian A Hübner

    Institute of Human Genetics, University Hospital Jena, Jena, Germany
    For correspondence
    christian.huebner@med.uni-jena.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1030-4943

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.

Reviewing Editor

  1. Marla B Feller, University of California, Berkeley, United States

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).

Version history

  1. Preprint posted: July 5, 2021 (view preprint)
  2. Received: July 16, 2021
  3. Accepted: February 6, 2022
  4. Accepted Manuscript published: February 7, 2022 (version 1)
  5. Version of Record published: February 24, 2022 (version 2)

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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  1. Alena Maul
  2. Antje Kathrin Huebner
  3. Nicola Strenzke
  4. Tobias Moser
  5. Rudolf Rübsamen
  6. Saša Jovanovic
  7. Christian A Hübner
(2022)
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

Share this article

https://doi.org/10.7554/eLife.72251

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