title: Contralateral-noise effects on cochlear responses in anesthetized mice are dominated by feedback from an unknown pathway.
abstract: Suppression of ipsilateral distortion product otoacoustic emissions (DPOAEs) by contralateral noise is used in humans and animals to assay the strength of sound-evoked negative feedback from the medial olivocochlear (MOC) efferent pathway. However, depending on species and anesthesia, contributions of other feedback systems to the middle or inner ear can cloud the interpretation. Here, contributions of MOC and middle-ear muscle reflexes, as well as autonomic feedback, to contra-noise suppression in anesthetized mice are dissected by selectively eliminating each pathway by surgical transection, pharmacological blockade, or targeted gene deletion. When ipsilateral DPOAEs were evoked by low-level primaries, contra-noise suppression was typically ~1 dB with contra-noise levels around 95 dB SPL, and it always disappeared upon contralateral cochlear destruction. Lack of middle-ear muscle contribution was suggested by persistence of contra-noise suppression after paralysis with curare, tensor tympani cauterization, or section of the facial nerve. Contribution of cochlear sympathetics was ruled out by studying mutant mice lacking adrenergic signaling (dopamine β-hydroxylase knockouts). Surprisingly, contra-noise effects on low-level DPOAEs were also not diminished by eliminating the MOC system pharmacologically (strychnine), surgically, or by deletion of relevant cholinergic receptors (α9/α10). In contrast, when ipsilateral DPOAEs were evoked by high-level primaries, the contra-noise suppression, although comparable in magnitude, was largely eliminated by MOC blockade or section. Possible alternate pathways are discussed for the source of contra-noise-evoked effects at low ipsilateral levels.
authors.affiliation: Department of Otology and Laryngology, Harvard Medical School and Eaton-Peabody Laboratory, 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: Hajime
authors.initials: H
authors.lastname: Usubuchi
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Vetter
authors.forename: A Bélen
authors.initials: AB
authors.lastname: Elgoyhen
authors.forename: Steven A
authors.initials: SA
authors.lastname: Thomas
authors.forename: M Charles
authors.initials: MC
authors.lastname: Liberman
mesh_terms: D000344:Afferent Pathways / Q000502:physiology; D000768:Anesthesia, General; D000818:Animals; D001676:Biofeedback, Psychology / Q000502:physiology*; D003051:Cochlea / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000502:physiology*; D009847:Olivary Nucleus / Q000502:physiology*; D017084:Otoacoustic Emissions, Spontaneous / Q000502:physiology*; D059629:Signal-To-Noise Ratio