Journal
JOURNAL OF NEUROSCIENCE
Volume 34, Issue 2, Pages 434-445Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3085-13.2014
Keywords
auditory discrimination learning; Ca2+ channel; CACNA2D3; endbulb of Held; inner hair cell; spiral ganglion
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Funding
- RIMB (University of Kaiserslautern)
- DFG SFB [894]
- [EU-CAVNET MRTN-CT-2006-035367]
- [PP1608]
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The auxiliary subunit alpha(2)delta 3 modulates the expression and function of voltage-gated calcium channels. Here we show that alpha(2)delta 3 mRNA is expressed in spiral ganglion neurons and auditory brainstem nuclei and that the protein is required for normal acoustic responses. Genetic deletion of alpha(2)delta 3 led to impaired auditory processing, with reduced acoustic startle and distorted auditory brainstem responses. alpha(2)delta 3(-/-) 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 alpha(2)delta 3(-/-) mice demonstrated impaired transmission at these synapses. Together, our results identify a novel role for the alpha(2)delta 3 auxiliary subunit in the structure and function of specific synapses in the mammalian auditory pathway and in auditory processing disorders.
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