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The Journal of Neuroscience, December 15, 2002, 22(24):10838-10846

Efferent Protection from Acoustic Injury Is Mediated via alpha 9 Nicotinic Acetylcholine Receptors on Outer Hair Cells

Stéphane F. Maison1, Anne E. Luebke2, M. Charles Liberman1, and Jian Zuo3

1 Department of Otology and Laryngology, Harvard Medical School and Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114, 2 Department of Otolaryngology and Neuroscience Program, University of Miami School of Medicine, Miami, Florida 33136, and 3 Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105

Exposure to intense sound can damage the mechanosensors of the inner ear and their afferent innervation. These neurosensory elements are innervated by a sound-activated feedback pathway, the olivocochlear efferent system. One major component of this system is cholinergic, and known cholinergic effects are mediated by the alpha 9/alpha 10 nicotinic acetylcholine receptor (nAChR) complex. Here, we show that overexpression of alpha 9 nAChR in the outer hair cells of bacterial artificial chromosome transgenic mice significantly reduces acoustic injury from exposures causing either temporary or permanent damage, without changing pre-exposure cochlear sensitivity to low- or moderate-level sound. These data demonstrate that efferent protection is mediated via the alpha 9 nAChR in the outer hair cells and provide direct evidence for a protective role, in vivo, of a member of the nAChR family.

Key words: olivocochlear; nicotinic; cholinergic; noise-induced hearing loss; transgenic mouse; cochlea


Copyright © 2002 Society for Neuroscience  0270-6474/02/222410838-09$05.00/0


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