RT Journal Article SR Electronic T1 Functional Role of GABAergic Innervation of the Cochlea: Phenotypic Analysis of Mice Lacking GABAA Receptor Subunits α1, α2, α5, α6, β2, β3, or δ JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 10315 OP 10326 DO 10.1523/JNEUROSCI.2395-06.2006 VO 26 IS 40 A1 Stéphane F. Maison A1 Thomas W. Rosahl A1 Gregg E. Homanics A1 M. Charles Liberman YR 2006 UL http://www.jneurosci.org/content/26/40/10315.abstract AB The olivocochlear efferent system is both cholinergic and GABAergic and innervates sensory cells and sensory neurons of the inner ear. Cholinergic effects on cochlear sensory cells are well characterized, both in vivo and in vitro; however, the robust GABAergic innervation is poorly understood. To explore the functional roles of GABA in the inner ear, we characterized the cochlear phenotype of seven mouse lines with targeted deletion of a GABAA receptor subunit (α1, α2, α5, α6, β2, β3, or δ). Four of the lines (α1, α2, α6, and δ) were normal: there was no cochlear histopathology, and cochlear responses suggested normal function of hair cells, afferent fibers, and efferent feedback. The other three lines (α5, β2, and β3) showed threshold elevations indicative of outer hair cell dysfunction. α5 and β2 lines also showed decreased effects of efferent bundle activation, associated with decreased density of efferent terminals on outer hair cells: although the onset of this degeneration was later in α5 (>6 weeks) than β2 (<6 weeks), both lines shows normal efferent development (up to 3 weeks). Two lines (β2 and β3) showed signs of neuropathy, either decreased density of afferent innervation (β3) or decreased neural responses without concomitant attenuation of hair cell responses (β2). One of the lines (β2) showed a clear sexual dimorphism in cochlear phenotype. Results suggest that the GABAergic component of the olivocochlear system contributes to the long-term maintenance of hair cells and neurons in the inner ear.