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  • Review Article
  • Published:

Auditory neuropathy — neural and synaptic mechanisms

Nature Reviews Neurology volume 12, pages 135–149 (2016)Cite this article

Subjects

Key Points

  • Auditory neuropathy impairs speech comprehension severely, beyond the extent that would be expected on the basis of increased threshold of audibility

  • Auditory neuropathy encompasses a range of disease mechanisms that typically disrupt the synaptic encoding and/or neural transmission of auditory information in the cochlea and auditory nerve

  • Auditory synaptopathy, impaired sound encoding at the synapses between inner hair cells and spiral ganglion neurons, results from genetic defects or insults such as exposure to loud noise

  • Advanced physiological and psychophysical testing combined with molecular genetic analysis facilitate diagnostics of auditory synaptopathy and neuropathy

  • Although traditional hearing aids often do not provide substantial benefit for patients with auditory synaptopathy or neuropathy, cochlear implants can provide effective hearing rehabilitation depending on the site(s) of disorder

Abstract

Sensorineural hearing impairment is the most common form of hearing loss, and encompasses pathologies of the cochlea and the auditory nerve. Hearing impairment caused by abnormal neural encoding of sound stimuli despite preservation of sensory transduction and amplification by outer hair cells is known as 'auditory neuropathy'. This term was originally coined for a specific type of hearing impairment affecting speech comprehension beyond changes in audibility: patients with this condition report that they “can hear but cannot understand”. This type of hearing impairment can be caused by damage to the sensory inner hair cells (IHCs), IHC ribbon synapses or spiral ganglion neurons. Human genetic and physiological studies, as well as research on animal models, have recently shown that disrupted IHC ribbon synapse function — resulting from genetic alterations that affect presynaptic glutamate loading of synaptic vesicles, Ca2+ influx, or synaptic vesicle exocytosis — leads to hearing impairment termed 'auditory synaptopathy'. Moreover, animal studies have demonstrated that sound overexposure causes excitotoxic loss of IHC ribbon synapses. This mechanism probably contributes to hearing disorders caused by noise exposure or age-related hearing loss. This Review provides an update on recently elucidated sensory, synaptic and neural mechanisms of hearing impairment, their corresponding clinical findings, and discusses current rehabilitation strategies as well as future therapies.

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Figure 1: Clinical neurophysiology for definitive diagnosis of auditory neuropathy.
Figure 2: Disorders affecting inner hair cells (IHCs), their afferent synapses or spiral ganglion neurons (SGNs) degrade the neural representation of sound.
Figure 3: The afferent ribbon synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs).
Figure 4: Otoferlin has an essential role at the inner hair cell (IHC) ribbon synapse.
Figure 5: Hair cells use the vesicular glutamate transporter 3 to load synaptic vesicles with glutamate.
Figure 6: Irreversible loss of inner hair cell (IHC) ribbon synapses during exposure to loud noise in mice.

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Acknowledgements

The authors would like to thank Drs Nicola Strenzke and Regis Nouvian for feedback on the manuscript, Dr Carolin Wichmann for the electron micrograph in Figure 3 and Dr Nouvian for providing artwork for Figures 3 and 4.

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Authors and Affiliations

  1. Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, 37099, Germany

    Tobias Moser

  2. Center for Hearing Research, University of California, Irvine, 92697, California, USA

    Arnold Starr

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  1. Tobias Moser
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  2. Arnold Starr
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Both authors researched the literature, assembled the Figures, and wrote, edited and revised the manuscript.

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Correspondence to Tobias Moser.

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Glossary

Auditory neuropathy

A hearing impairment found in individuals with hereditary motor and sensory neuropathy; impairs speech comprehension beyond what would be expected on the basis of pure tone audiograms.

Ribbon synapses

Highly specialized synapses between the inner hair cells and spiral ganglion neurons, with an electron-dense structure — the synaptic ribbon — at the presynaptic active zone that mediates neurotransmitter release.

Cochlear microphone potentials

Outer hair cells generate local cochlear potentials that follow the sound stimulus so precisely that they are called 'microphone potentials'.

Otoacoustic emission

Sound generated from within the inner ear that can be measured with a sensitive microphone in the external ear canal to assess outer hair cell function.

Auditory brainstem responses

Evoked potentials in response to repetitive acoustic stimulation that are recorded from scalp EEG electrodes and typically have five peaks, referred to as waves I–V.

Spiral ganglion compound action potential

The first auditory brainstem response peak, wave I, reflects the spiral ganglion compound action potential; this potential can be recorded with better resolution using electrocochleography.

Auditory synaptopathy

Hearing impairment caused by dysfunction or loss of ribbon synapses in the inner hair cells; has been termed auditory synaptopathy and can show clinical findings similar to those described above for auditory neuropathy.

Organ of Corti

The organ of Corti is the end organ of the sense of hearing that harbours the sensory inner and outer hair cells, as well as afferent and efferent nerve fibres and various types of supporting cells.

Compound action potential

Reflects the synchronized firing of spiral ganglion neurons; assessed by intrameatal or transtympanic electrocochleography.

Glutamate excitotoxicity

Excessive presynaptic glutamate release leading to massive depolarization and subsequent synapse loss.

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Moser, T., Starr, A. Auditory neuropathy — neural and synaptic mechanisms. Nat Rev Neurol 12, 135–149 (2016). https://doi.org/10.1038/nrneurol.2016.10

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