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Loss of GABAB receptors in cochlear neurons: threshold elevation suggests modulation of outer hair cell function by type II afferent fibers

Maison, Stéphane F. and Casanova, Emilio and Holstein, Gay R. and Bettler, Bernhard and Liberman, M. Charles. (2009) Loss of GABAB receptors in cochlear neurons: threshold elevation suggests modulation of outer hair cell function by type II afferent fibers. Journal of the Association for Research in Otolaryngology, Vol. 10, no. 1. pp. 50-63.

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Official URL: http://edoc.unibas.ch/dok/A5262212

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Abstract

Despite pharmacological and immunohistochemical evidence for GABA as a neurotransmitter in the olivocochlear efferent bundle, a clear functional role of GABA in the inner ear has not emerged. To explore the role of metabotropic GABA(B) receptors, we characterized the cochlear phenotype of mice with targeted deletion of the GABA(B1) subunit and determined its tissue localization using a mouse line expressing a GFP-tagged GABA(B1) subunit under the endogenous promoter. Immunostaining revealed GABA(B1) expression in both type I and type II ganglion cells and in their synaptic terminals under inner and outer hair cells, respectively. No GABA(B1) expression was observed in hair cells. Mean cochlear thresholds, measured via both auditory brainstem responses and distortion product otoacoustic emissions (DPOAEs), were elevated by approximately 10 dB in GABA(B1)-deficient mice, consistent with outer hair cell dysfunction. Olivocochlear efferent function, assessed via DPOAE suppression during efferent electrical stimulation, was unaffected by GABA(B1) deletion. GABA(B1)-deficient mice showed increased resistance to permanent acoustic injury, with mean threshold shifts approximately 25 dB smaller than wild-types after exposure to 8-16-kHz noise at 100 dB for 2 h. In contrast, there was no vulnerability difference to temporary acoustic injury following exposure to the same noise at 94 dB for 15 min. Our results suggest that GABAergic signaling in type II afferent neurons may be required for normal outer hair cell amplifier function at low sound levels and may also modulate outer hair cell responses to high-level sound.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Physiology > Molecular Neurobiology Synaptic Plasticity (Bettler)
UniBasel Contributors:Bettler, Bernhard
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Springer
ISSN:1525-3961
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:04 Jan 2013 08:37
Deposited On:22 Mar 2012 13:37

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