TY - JOUR T1 - α<sub>2</sub>δ3 Is Essential for Normal Structure and Function of Auditory Nerve Synapses and Is a Novel Candidate for Auditory Processing Disorders JF - The Journal of Neuroscience JO - J. Neurosci. SP - 434 LP - 445 DO - 10.1523/JNEUROSCI.3085-13.2014 VL - 34 IS - 2 AU - Antonella Pirone AU - Simone Kurt AU - Annalisa Zuccotti AU - Lukas Rüttiger AU - Peter Pilz AU - David H. Brown AU - Christoph Franz AU - Michaela Schweizer AU - Marco B. Rust AU - Rudolf Rübsamen AU - Eckhard Friauf AU - Marlies Knipper AU - Jutta Engel Y1 - 2014/01/08 UR - http://www.jneurosci.org/content/34/2/434.abstract N2 - 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. ER -