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J Neurosci. 2014 Jan 8;34(2):434-45. doi: 10.1523/JNEUROSCI.3085-13.2014.

α2δ3 is essential for normal structure and function of auditory nerve synapses and is a novel candidate for auditory processing disorders.

Author information

1
University of Tübingen, Department of Otolaryngology, Tübingen Hearing Research Centre, Molecular Physiology of Hearing, 72076 Tübingen, Germany, Cluster of Excellence "Hearing4all," Institute of Audioneurotechnology and Hannover Medical School, Department of Experimental Otology, ENT Clinics, 30625 Hannover, Germany, University of Ulm, Institute of Neurobiology, 89081 Ulm, Germany, University of Tübingen, Institute of Neurobiology, 72076 Tübingen, Germany, University of Leipzig, Institute of Biology II, 04103 Leipzig, Germany, University of Hamburg, Center for Molecular Neurobiology, 20251 Hamburg, Germany, University of Kaiserslautern, Department of Biology, Neurobiology/Neurophysiology Group, 67653 Kaiserslautern, Germany, University of Kaiserslautern, Department of Biology, Animal Physiology Group, 67653 Kaiserslautern, Germany, University of Tübingen, Department of Physiology II and Tübingen Hearing Research Centre, 72076 Tübingen, Germany, and Saarland University, Department of Biophysics, 66421 Homburg/Saar, Germany.

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 Ca(2+) 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.

KEYWORDS:

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

PMID:
24403143
DOI:
10.1523/JNEUROSCI.3085-13.2014
[Indexed for MEDLINE]
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