Auditory neuropathy — neural and synaptic mechanisms

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

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Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS CONDUCTIVE HEARING LOSS DURING DEVELOPMENT DOES NOT APPRECIABLY ALTER THE SHARPNESS OF COCHLEAR TUNING Article

Open access 17 February 2021 DEAFNESS: FROM GENETIC ARCHITECTURE TO GENE THERAPY Article 12 May 2023 AN INTEGRATIVE APPROACH FOR PEDIATRIC AUDITORY NEUROPATHY SPECTRUM DISORDERS: REVISITING

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references 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. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Institute for Auditory Neuroscience and InnerEarLab, University Medical Center

Göttingen, Göttingen, 37099, Germany Tobias Moser * Center for Hearing Research, University of California, Irvine, 92697, California, USA Arnold Starr Authors * Tobias Moser View author

publications You can also search for this author inPubMed Google Scholar * Arnold Starr View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS

Both authors researched the literature, assembled the Figures, and wrote, edited and revised the manuscript. CORRESPONDING AUTHOR Correspondence to Tobias Moser. ETHICS DECLARATIONS

COMPETING INTERESTS The authors declare no competing financial interests. RELATED LINKS FURTHER INFORMATION MITOchondrial DYNamics variation pages is a portal specializing in genes involved

in disorders of mitochondrial dynamics, and describes the known human OPA1 mutations POWERPOINT SLIDES POWERPOINT SLIDE FOR FIG. 1 POWERPOINT SLIDE FOR FIG. 2 POWERPOINT SLIDE FOR FIG. 3

POWERPOINT SLIDE FOR FIG. 4 POWERPOINT SLIDE FOR FIG. 5 POWERPOINT SLIDE FOR FIG. 6 POWERPOINT SLIDE FOR TABLE 1 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. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Published: 19 February 2016 * Issue Date: March 2016 * DOI:

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