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J Neurophysiol 97: 3269-3278, 2007. First published March 7, 2007; doi:10.1152/jn.00067.2007
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A Novel Effect of Cochlear Efferents: In Vivo Response Enhancement Does Not Require {alpha}9 Cholinergic Receptors

Stéphane F. Maison1, Douglas E. Vetter2 and M. Charles Liberman1,3

1Department of Otology and Laryngology, Harvard Medical School and Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston; 2Tufts University School of Medicine, Department of Neuroscience, Boston; and 3Division of Health Science and Technology, Harvard University/Massachusetts Institute of Technology, Cambridge, Massachusetts

Submitted 19 January 2007; accepted in final form 2 March 2007

Outer hair cells in the mammalian cochlea receive a cholinergic efferent innervation that constitutes the effector arm of a sound-evoked negative feedback loop. The well-studied suppressive effects of acetylcholine (ACh) release from efferent terminals are mediated by {alpha}9/{alpha}10 ACh receptors and are potently blocked by strychnine. Here, we report a novel, efferent-mediated enhancement of cochlear sound-evoked neural responses and otoacoustic emissions in mice. In controls, a slow enhancement of response amplitude to supranormal levels appears after recovery from the classic suppressive effects seen during a 70-s epoch of efferent shocks. The magnitude of post-shock enhancement can be as great as 10 dB and tends to be greater for high-frequency acoustic stimuli. Systemic strychnine at 10 mg/kg eliminates efferent-induced suppression, revealing a purely enhancing effect of efferent shocks, which peaks within 5 s after efferent-stimulation onset, maintains a constant level through the stimulation epoch, and slowly decays back to baseline with a time constant of ~100 s. In mice with targeted deletion of the {alpha}9 ACh receptor subunit, efferent-evoked effects resemble those in wild types with strychnine blockade, further showing that this novel efferent effect is fundamentally different from all cholinergic effects previously reported.

Address for reprint requests and other correspondence: S. F. Maison, Massachusetts Eye and Ear Infirmary, 243 Charles St., Boston, MA 02114-3096 (E-mail: stephane_maison{at}meei.harvard.edu)




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D. E. Vetter, E. Katz, S. F. Maison, J. Taranda, S. Turcan, J. Ballestero, M. C. Liberman, A. B. Elgoyhen, and J. Boulter
The {alpha}10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system
PNAS, December 18, 2007; 104(51): 20594 - 20599.
[Abstract] [Full Text] [PDF]


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