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Articles, Cellular/Molecular

α2δ3 Is Essential for Normal Structure and Function of Auditory Nerve Synapses and Is a Novel Candidate for Auditory Processing Disorders

Antonella Pirone, Simone Kurt, Annalisa Zuccotti, Lukas Rüttiger, Peter Pilz, David H. Brown, Christoph Franz, Michaela Schweizer, Marco B. Rust, Rudolf Rübsamen, Eckhard Friauf, Marlies Knipper and Jutta Engel
Journal of Neuroscience 8 January 2014, 34 (2) 434-445; DOI: https://doi.org/10.1523/JNEUROSCI.3085-13.2014
Antonella Pirone
1University of Tübingen, Department of Otolaryngology, Tübingen Hearing Research Centre, Molecular Physiology of Hearing, 72076 Tübingen, Germany,
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Simone Kurt
2Cluster of Excellence “Hearing4all,” Institute of Audioneurotechnology and Hannover Medical School, Department of Experimental Otology, ENT Clinics, 30625 Hannover, Germany,
3University of Ulm, Institute of Neurobiology, 89081 Ulm, Germany,
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Annalisa Zuccotti
1University of Tübingen, Department of Otolaryngology, Tübingen Hearing Research Centre, Molecular Physiology of Hearing, 72076 Tübingen, Germany,
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Lukas Rüttiger
1University of Tübingen, Department of Otolaryngology, Tübingen Hearing Research Centre, Molecular Physiology of Hearing, 72076 Tübingen, Germany,
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Peter Pilz
4University of Tübingen, Institute of Neurobiology, 72076 Tübingen, Germany,
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David H. Brown
5University of Leipzig, Institute of Biology II, 04103 Leipzig, Germany,
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Christoph Franz
1University of Tübingen, Department of Otolaryngology, Tübingen Hearing Research Centre, Molecular Physiology of Hearing, 72076 Tübingen, Germany,
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Michaela Schweizer
6University of Hamburg, Center for Molecular Neurobiology, 20251 Hamburg, Germany,
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Marco B. Rust
7University of Kaiserslautern, Department of Biology, Neurobiology/Neurophysiology Group, 67653 Kaiserslautern, Germany,
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Rudolf Rübsamen
5University of Leipzig, Institute of Biology II, 04103 Leipzig, Germany,
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Eckhard Friauf
8University of Kaiserslautern, Department of Biology, Animal Physiology Group, 67653 Kaiserslautern, Germany,
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Marlies Knipper
1University of Tübingen, Department of Otolaryngology, Tübingen Hearing Research Centre, Molecular Physiology of Hearing, 72076 Tübingen, Germany,
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Jutta Engel
9University of Tübingen, Department of Physiology II and Tübingen Hearing Research Centre, 72076 Tübingen, Germany, and
10Saarland University, Department of Biophysics, 66421 Homburg/Saar, Germany
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Abstract

The auxiliary subunit α2δ3 modulates the expression and function of voltage-gated calcium channels. Here we show that α2δ3 mRNA is expressed in spiral ganglion neurons and auditory brainstem nuclei and that the protein is required for normal acoustic responses. Genetic deletion of α2δ3 led to impaired auditory processing, with reduced acoustic startle and distorted auditory brainstem responses. α2δ3−/− mice learned to discriminate pure tones, but they failed to discriminate temporally structured amplitude-modulated tones. Light and electron microscopy analyses revealed reduced levels of presynaptic Ca2+ channels and smaller auditory nerve fiber terminals contacting cochlear nucleus bushy cells. Juxtacellular in vivo recordings of sound-evoked activity in α2δ3−/− mice demonstrated impaired transmission at these synapses. Together, our results identify a novel role for the α2δ3 auxiliary subunit in the structure and function of specific synapses in the mammalian auditory pathway and in auditory processing disorders.

  • auditory discrimination learning
  • Ca2+ channel
  • CACNA2D3
  • endbulb of Held
  • inner hair cell
  • spiral ganglion
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The Journal of Neuroscience: 34 (2)
Journal of Neuroscience
Vol. 34, Issue 2
8 Jan 2014
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α2δ3 Is Essential for Normal Structure and Function of Auditory Nerve Synapses and Is a Novel Candidate for Auditory Processing Disorders
Antonella Pirone, Simone Kurt, Annalisa Zuccotti, Lukas Rüttiger, Peter Pilz, David H. Brown, Christoph Franz, Michaela Schweizer, Marco B. Rust, Rudolf Rübsamen, Eckhard Friauf, Marlies Knipper, Jutta Engel
Journal of Neuroscience 8 January 2014, 34 (2) 434-445; DOI: 10.1523/JNEUROSCI.3085-13.2014

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α2δ3 Is Essential for Normal Structure and Function of Auditory Nerve Synapses and Is a Novel Candidate for Auditory Processing Disorders
Antonella Pirone, Simone Kurt, Annalisa Zuccotti, Lukas Rüttiger, Peter Pilz, David H. Brown, Christoph Franz, Michaela Schweizer, Marco B. Rust, Rudolf Rübsamen, Eckhard Friauf, Marlies Knipper, Jutta Engel
Journal of Neuroscience 8 January 2014, 34 (2) 434-445; DOI: 10.1523/JNEUROSCI.3085-13.2014
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Keywords

  • auditory discrimination learning
  • Ca2+ channel
  • CACNA2D3
  • endbulb of Held
  • inner hair cell
  • spiral ganglion

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