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The Journal of Neuroscience, October 4, 2006, 26(40):10315-10326; doi:10.1523/JNEUROSCI.2395-06.2006

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Cellular/Molecular
Functional Role of GABAergic Innervation of the Cochlea: Phenotypic Analysis of Mice Lacking GABA_A Receptor Subunits 1, 2, 5, 6, 2, 3, or

Stéphane F. Maison,¹ Thomas W. Rosahl,² Gregg E. Homanics,³ and M. Charles Liberman¹

¹Department of Otology and Laryngology, Harvard Medical School and Eaton–Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114, ²Neuroscience Research Center, Merck Sharp and Dohme Research Laboratories, Harlow, Essex CM20 2QR, United Kingdom, and ³Departments of Anesthesiology and Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260

Correspondence should be addressed to Dr. Stéphane F. Maison, Eaton–Peabody Laboratory, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114-3096. Email: stephane_maison{at}meei.harvard.edu

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 GABA_A receptor subunit (1, 2, 5, 6, 2, 3, or ). Four of the lines (1, 2, 6, and ) 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 (5, 2, and 3) showed threshold elevations indicative of outer hair cell dysfunction. 5 and 2 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 5 (>6 weeks) than 2 (<6 weeks), both lines shows normal efferent development (up to 3 weeks). Two lines (2 and 3) showed signs of neuropathy, either decreased density of afferent innervation (3) or decreased neural responses without concomitant attenuation of hair cell responses (2). One of the lines (2) 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.

Key words: efferent; hair cell; olivocochlear; auditory; feedback; knock-out mice

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Received Sept. 13, 2005; revised Aug. 25, 2006; accepted Aug. 29, 2006.

Correspondence should be addressed to Dr. Stéphane F. Maison, Eaton–Peabody Laboratory, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114-3096. Email: stephane_maison{at}meei.harvard.edu

This article has been cited by other articles:

				S. F. Maison, D. E. Vetter, and M. C. Liberman A Novel Effect of Cochlear Efferents: In Vivo Response Enhancement Does Not Require {alpha}9 Cholinergic Receptors J Neurophysiol, May 1, 2007; 97(5): 3269 - 3278. [Abstract] [Full Text] [PDF]

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