title: A novel effect of cochlear efferents: in vivo response enhancement does not require alpha9 cholinergic receptors.
abstract: 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 alpha9/alpha10 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 approximately 100 s. In mice with targeted deletion of the alpha9 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.
authors.affiliation: Department of Otology and Laryngology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA 02114-3096, USA. stephane_maison@meei.harvard.edu
authors.forename: Stéphane F
authors.initials: SF
authors.lastname: Maison
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Vetter
authors.forename: M Charles
authors.initials: MC
authors.lastname: Liberman
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000161:Acoustic Stimulation / Q000379:methods; D000818:Animals; D003051:Cochlea / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004307:Dose-Response Relationship, Radiation; D004525:Efferent Pathways / Q000187:drug effects / Q000502:physiology*; D005072:Evoked Potentials, Auditory / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D018684:Glycine Agents / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects / Q000502:physiology*; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*; D013331:Strychnine / Q000494:pharmacology; D013997:Time Factors
chemical_list: C402445:Chrna9 protein, mouse; D018684:Glycine Agents; D011978:Receptors, Nicotinic; D013331:Strychnine; D000109:Acetylcholine