title: Review of hair cell synapse defects in sensorineural hearing impairment.
abstract: OBJECTIVE
  To review new insights into the pathophysiology of sensorineural hearing impairment. Specifically, we address defects of the ribbon synapses between inner hair cells and spiral ganglion neurons that cause auditory synaptopathy.
  
  
  METHODS
  Here, we review original publications on the genetics, animal models, and molecular mechanisms of hair cell ribbon synapses and their dysfunction.
  
  
  CONCLUSIONS
  Hair cell ribbon synapses are highly specialized to enable indefatigable sound encoding with utmost temporal precision. Their dysfunctions, which we term auditory synaptopathies, impair audibility of sounds to varying degrees but commonly affect neural encoding of acoustic temporal cues essential for speech comprehension. Clinical features of auditory synaptopathies are similar to those accompanying auditory neuropathy, a group of genetic and acquired disorders of spiral ganglion neurons. Genetic auditory synaptopathies include alterations of glutamate loading of synaptic vesicles, synaptic Ca influx or synaptic vesicle turnover. Acquired synaptopathies include noise-induced hearing loss because of excitotoxic synaptic damage and subsequent gradual neural degeneration. Alterations of ribbon synapses likely also contribute to age-related hearing loss.
authors.affiliation: InnerEarLab, Department of Otolaryngology, University of Göttingen Medical School, Göttingen, Germany. tmoser@gwdg.de
authors.forename: Tobias
authors.initials: T
authors.lastname: Moser
authors.forename: Friederike
authors.initials: F
authors.lastname: Predoehl
authors.forename: Arnold
authors.initials: A
authors.lastname: Starr
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D003638:Deafness / Q000235:genetics / Q000503:physiopathology; D018698:Glutamic Acid / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000473:pathology / Q000502:physiology*; D034381:Hearing Loss / Q000503:physiopathology; D006317:Hearing Loss, Noise-Induced / Q000235:genetics / Q000503:physiopathology; D006319:Hearing Loss, Sensorineural / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D013569:Synapses / Q000473:pathology / Q000502:physiology*; D050496:Vesicular Glutamate Transport Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; C118457:OTOF protein, human; D050496:Vesicular Glutamate Transport Proteins; D018698:Glutamic Acid