alpha(2)delta 3 Is Essential for Normal Structure and Function of Auditory Nerve Synapses and Is a Novel Candidate for Auditory Processing Disorders

作者：Pirone Antonella; Kurt Simone; Zuccotti Annalisa; Ruettiger Lukas; Pilz Peter; Brown David H; Franz Christoph; Schweizer Michaela; Rust Marco B; Ruebsamen Rudolf; Friauf Eckhard; Knipper Marlies; Engel Jutta^*

来源：Journal of Neuroscience, 2014, 34(2): 434-445.

DOI：10.1523/JNEUROSCI.3085-13.2014

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

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.

• 出版日期2014-1-8