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9 cholinergic receptors
1 Department of Otology & Laryngology, Harvard Medical School, Boston, Massachusetts, United States; Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
2 Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts, United States
* To whom correspondence should be addressed. E-mail: stephane_maison{at}meei.harvard.edu.
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
9/
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-sec 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 sec after efferent-stimulation onset, maintains a constant level through the stimulation epoch and then slowly decays back to baseline with a time constant of ~100 seconds. In mice with targeted deletion of the
9 ACh receptor subunit, efferent-evoked effects resemble those in wildtypes with strychnine blockade, further showing that this novel efferent effect is fundamentally different from all cholinergic effects previously reported.
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