ArticleProceedings of the National Academy of Sciences of the United States of America2015
Unmyelinated type II afferent neurons report cochlear damage.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 153 citations in OpenAlex.
- Article
- Upregulation of ATP-purinergic P2×2 receptors in the cochlea over-amplifies hearing sensitivity leading to hyperacusis and attenuation by antagonists.bioRxiv : the preprint server for biology · 2026Article
- Spontaneous Calcium Signalling in the Developing Mammalian Cochlea.Journal of the Association for Research in Otolaryngology : JARO · 2026Review
- Efferent Inhibition of Hair Cells: Past, Present and Future.Journal of the Association for Research in Otolaryngology : JARO · 2026Review
- Subtype-Specific Vulnerability of Spiral Ganglion Neurons in Sensorineural Hearing Loss Across the Lifespan.Brain sciences · 2026Review
- Cochlear histopathology in macaques after noise-induced temporary threshold shifts.Hearing research · 2026Article
- Scrt1-iCreER: An Inducible Mouse Model for Genetic Access to Type I Spiral Ganglion and Cochlear Nucleus Neurons.Molecular neurobiology · 2026Article
- Migraine-induced cochlear injury triggers ZBP1-mediated PANoptosis via CGRP signaling.The journal of headache and pain · 2026Article
- Expression of the P2X1 receptor remains in the type II spiral ganglion neurons in the mature rat cochlea.Purinergic signalling · 2026Article
- Medial Olivocochlear Efferent Modulation of Cochlear Micromechanics Requires P2X4 Receptor in Outer Hair Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Recent preclinical and clinical advances in gene therapy for hereditary hearing loss.Molecules and cells · 2025Review
- Endocochlear potential contributes to hair cell death in TMPRSS3 hearing loss.The Journal of clinical investigation · 2025Article
- EPHRIN-A1 and -A2 act as positive growth factors for developing spiral ganglion radial bundles.Developmental biology · 2025Article
- ATP-gated P2x7 receptors express at type II auditory nerves and required for efferent hearing control and noise protection.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Virally mediated enhancement of efferent inhibition reduces acoustic trauma in wild-type murine cochleas.Molecular therapy. Methods & clinical development · 2025Article
- Subcellular localization of the P2X4 receptor in sensory hair cells of Wistar rat cochlea.Histochemistry and cell biology · 2025Article
- Phenotypic changes of auditory nerve fibers after excitotoxicity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Developmental differentiation of mouse inner ear neuron subpopulations resolved with a peripherin-promoter reporter within the Grm8 locus.Scientific reports · 2025Article
- GABAergic synapses between auditory efferent neurons and type II spiral ganglion afferent neurons in the mouse cochlea.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Clinical phenotype and management of sound-induced pain: Insights from adults with pain hyperacusis.The journal of pain · 2025Article
34 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
In the mammalian cochlea, acoustic information is carried to the brain by the predominant (95%) large-diameter, myelinated type I afferents, each of which is postsynaptic to a single inner hair cell. The remaining thin, unmyelinated type II afferents extend hundreds of microns along the cochlear duct to contact many outer hair cells. Despite this extensive arbor, type II afferents are weakly activated by outer hair cell transmitter release and are insensitive to sound. Intriguingly, type II afferents remain intact in damaged regions of the cochlea. Here, we show that type II afferents are activated when outer hair cells are damaged. This response depends on both ionotropic (P2X) and metabotropic (P2Y) purinergic receptors, binding ATP released from nearby supporting cells in response to hair cell damage. Selective activation of P2Y receptors increased type II afferent excitability by the closure of KCNQ-type potassium channels, a potential mechanism for the painful hypersensitivity (that we term "noxacusis" to distinguish from hyperacusis without pain) that can accompany hearing loss. Exposure to the KCNQ channel activator retigabine suppressed the type II fiber's response to hair cell damage. Type II afferents may be the cochlea's nociceptors, prompting avoidance of further damage to the irreparable inner ear.
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