Is noise-induced cochlear neuropathy key to the generation of hyperacusis or tinnitus?

J Neurophysiol. 2014 Feb;111(3):552-64. doi: 10.1152/jn.00184.2013. Epub 2013 Nov 6.


Perceptual abnormalities such as hyperacusis and tinnitus often occur after acoustic overexposure. Although such exposure can also result in permanent threshold elevation, some individuals with noise-induced hyperacusis or tinnitus show clinically normal thresholds. Recent work in animals has shown that a "neuropathic" noise exposure can cause immediate, permanent degeneration of the cochlear nerve despite complete threshold recovery and lack of hair cell damage (Kujawa SG, Liberman MC. J Neurosci 29: 14077-14085, 2009; Lin HW, Furman AC, Kujawa SG, Liberman MC. J Assoc Res Otolaryngol 12: 605-616, 2011). Here we ask whether this noise-induced primary neuronal degeneration results in abnormal auditory behavior, based on the acoustic startle response (ASR) and prepulse inhibition (PPI) of startle. Responses were measured in mice exposed either to a "neuropathic" noise or to a lower-intensity, "nonneuropathic" noise and in unexposed control mice. Mice with cochlear neuropathy displayed hyperresponsivity to sound, evidenced by enhanced ASR and PPI, while exposed mice without neuronal loss showed control-like responses. Gap PPI tests, often used to assess tinnitus, revealed limited gap detection deficits in mice with cochlear neuropathy only for certain gap-startle latencies, inconsistent with the presence of tinnitus "filling in the gap." Despite significantly reduced wave 1 of the auditory brainstem response, representing cochlear nerve activity, later peaks were unchanged or enhanced, suggesting compensatory neural hyperactivity in the auditory brainstem. Considering the rapid postexposure onset of both cochlear neuropathy and exaggerated startle-based behavior, the results suggest a role for cochlear primary neuronal degeneration, per se, in the central neural excitability that could underlie the generation of hyperacusis.

Keywords: acoustic startle response; acoustic trauma; auditory brainstem response; noise-induced hearing loss; prepulse inhibition.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death
  • Cochlear Nerve / pathology
  • Cochlear Nerve / physiopathology*
  • Hyperacusis / etiology
  • Hyperacusis / physiopathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / pathology
  • Neurons / physiology
  • Noise / adverse effects*
  • Sensory Gating*
  • Tinnitus / etiology
  • Tinnitus / physiopathology*
  • Vestibulocochlear Nerve Diseases / etiology
  • Vestibulocochlear Nerve Diseases / physiopathology*