Review of hair cell synapse defects in sensorineural hearing impairment

Otol Neurotol. 2013 Aug;34(6):995-1004. doi: 10.1097/MAO.0b013e3182814d4a.


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.

Data sources and study selection: Here, we review original publications on the genetics, animal models, and molecular mechanisms of hair cell ribbon synapses and their dysfunction.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / physiology
  • Animals
  • Deafness / genetics
  • Deafness / physiopathology
  • Glutamic Acid / metabolism
  • Hair Cells, Auditory / pathology
  • Hair Cells, Auditory / physiology*
  • Hearing Loss / physiopathology
  • Hearing Loss, Noise-Induced / genetics
  • Hearing Loss, Noise-Induced / physiopathology
  • Hearing Loss, Sensorineural / genetics
  • Hearing Loss, Sensorineural / physiopathology*
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology
  • Mice
  • Synapses / pathology
  • Synapses / physiology*
  • Vesicular Glutamate Transport Proteins / genetics
  • Vesicular Glutamate Transport Proteins / metabolism


  • Membrane Proteins
  • OTOF protein, human
  • Vesicular Glutamate Transport Proteins
  • Glutamic Acid