title: Re-Emergent Inhibition of Cochlear Inner Hair Cells in a Mouse Model of Hearing Loss.
abstract: Hearing loss among the elderly correlates with diminished social, mental, and physical health. Age-related cochlear cell death does occur, but growing anatomical evidence suggests that synaptic rearrangements on sensory hair cells also contribute to auditory functional decline. Here we present voltage-clamp recordings from inner hair cells of the C57BL/6J mouse model of age-related hearing loss, which reveal that cholinergic synaptic inputs re-emerge during aging. These efferents are functionally inhibitory, using the same ionic mechanisms as do efferent contacts present transiently before the developmental onset of hearing. The strength of efferent inhibition of inner hair cells increases with hearing threshold elevation. These data indicate that the aged cochlea regains features of the developing cochlea and that efferent inhibition of the primary receptors of the auditory system re-emerges with hearing impairment.
  
  
  CONCLUSIONS
  Synaptic changes in the auditory periphery are increasingly recognized as important factors in hearing loss. To date, anatomical work has described the loss of afferent contacts from cochlear hair cells. However, relatively little is known about the efferent innervation of the cochlea during hearing loss. We performed intracellular recordings from mouse inner hair cells across the lifespan and show that efferent innervation of inner hair cells arises in parallel with the loss of afferent contacts and elevated hearing threshold during aging. These efferent neurons inhibit inner hair cells, raising the possibility that they play a role in the progression of age-related hearing loss.
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Centers for Sensory Biology and Hearing and Balance, Johns Hopkins School of Medicine, Baltimore, Maryland 21205.
authors.forename: Stephen Paul
authors.initials: SP
authors.lastname: Zachary
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Department of Otolaryngology, and Centers for Sensory Biology and Hearing and Balance, Johns Hopkins School of Medicine, Baltimore, Maryland 21205 pfuchs1@jhmi.edu.
authors.forename: Paul Albert
authors.identifier: http://orcid.org/0000-0003-4627-4114
authors.initials: PA
authors.lastname: Fuchs
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000367:Age Factors; D000429:Alcohol Oxidoreductases; D000818:Animals; D000831:Animals, Newborn; D001030:Apamin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D056970:Co-Repressor Proteins; D003051:Cochlea / Q000473:pathology*; D020916:Conotoxins / Q000494:pharmacology; D003472:Curare / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects / Q000502:physiology; D005260:Female; D018684:Glycine Agents / Q000494:pharmacology; D006199:Hair Cells, Auditory, Inner / Q000502:physiology*; D034381:Hearing Loss / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000502:physiology*; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D013331:Strychnine / Q000494:pharmacology
chemical_list: C491142:ACV1, Conus textile; D002121:Calcium Channel Blockers; D056970:Co-Repressor Proteins; D020916:Conotoxins; D004268:DNA-Binding Proteins; D018684:Glycine Agents; D003473:Neuromuscular Nondepolarizing Agents; D010750:Phosphoproteins; D001030:Apamin; D003472:Curare; D000429:Alcohol Oxidoreductases; C111341:Ctbp2 protein, mouse; D013331:Strychnine; D000109:Acetylcholine
keywords: age-related hearing loss; cholinergic inhibition; cochlea; inner hair cell; olivocochlear system; synaptic transmission