title: Efferent feedback minimizes cochlear neuropathy from moderate noise exposure.
abstract: Although protective effects of the cochlea's efferent feedback pathways have been well documented, prior work has focused on hair cell damage and cochlear threshold elevation and, correspondingly, on the high sound pressure levels (>100 dB SPL) necessary to produce them. Here we explore the noise-induced loss of cochlear neurons that occurs with lower-intensity exposures and in the absence of permanent threshold shifts. Using confocal microscopy to count synapses between hair cells and cochlear nerve fibers, and using measurement of auditory brainstem responses and otoacoustic emissions to assess cochlear presynaptic and postsynaptic function, we compare the damage from a weeklong exposure to moderate-level noise (84 dB SPL) in mice with varying degrees of cochlear de-efferentation induced by surgical lesion to the olivocochlear pathway. Such exposure causes minimal acute threshold shifts and no chronic shifts in mice with normal efferent feedback. In de-efferented animals, there was up to 40% loss of cochlear nerve synapses and a corresponding decline in the amplitude of the auditory brainstem response. Quantitative analysis of the de-efferentation in inner versus outer hair cell areas suggested that outer hair cell efferents are the most important in minimizing this neuropathy, presumably by virtue of their sound-evoked feedback reduction of cochlear amplification. The moderate nature of this acoustic overexposure suggests that cochlear neurons are at risk even in everyday acoustic environments, so the need for cochlear protection is plausible as a driving force in the design of this feedback pathway.
authors.affiliation: Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts 02114, 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: M Charles
authors.initials: MC
authors.lastname: Liberman
mesh_terms: D000161:Acoustic Stimulation; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D001933:Brain Stem / Q000293:injuries; D003051:Cochlea / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D025461:Feedback, Physiological / Q000502:physiology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009476:Neurons, Efferent / Q000502:physiology*; D009622:Noise; D017084:Otoacoustic Emissions, Spontaneous / Q000502:physiology; D018091:Receptors, AMPA / Q000378:metabolism; D013997:Time Factors; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism; D000160:Vestibulocochlear Nerve Diseases / Q000503:physiopathology*
chemical_list: D004268:DNA-Binding Proteins; D018091:Receptors, AMPA; D050494:Vesicular Acetylcholine Transport Proteins; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein; C104722:glutamate receptor ionotropic, AMPA 2
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