Abstract
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. Here, we review original publications on the genetics, animal models, and molecular mechanisms of hair cell ribbon synapses and their dysfunction. 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.
Highlights
Journal Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 34(6)
The mouse model allows for analysis of Ca2+ influx and the ensuing exocytosis in inner hair cells, which were both reduced by 90% [46] (Fig. 2C, D)
Auditory synaptopathy-impaired synaptic sound encoding has only recently been appreciated as a disease mechanism of both genetic and acquired hearing impairments
Summary
We address defects of the ribbon synapses between inner hair cells and spiral ganglion neurons that cause auditory synaptopathy. 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. Based on human temporal bone histology Schuknecht and Igarashi [1] proposed a nosology for slowly progressing sensorineural hearing loss They distinguished conditions affecting stria vascularis (disrupting cochlear ion homeostasis and energetics), organ of Corti (disrupting hair cell function), and neurons (disrupting transmission of auditory information to the brain). While sharing some of the common scaffold proteins of the active zone, the hair cell ribbon synapse seems to otherwise employ different proteins than most other synapses (39Y44) (Fig. 1C), some of which have been shown to be affected in hereditary synaptopathic hearing impairment
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