ArticlePLoS biology2009
A point mutation in the hair cell nicotinic cholinergic receptor prolongs cochlear inhibition and enhances noise protection.
Article in PLoS biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 136 citations in OpenAlex.
- Efferent Inhibition of Hair Cells: Past, Present and Future.Journal of the Association for Research in Otolaryngology : JARO · 2026Review
- Impaired Development of the Medial Olivocochlear System in a KCNQ4-Deficient Mouse Model.Molecular neurobiology · 2026Article
- Drug Discovery Targeting Nicotinic Acetylcholine Receptors for Hearing Loss.International journal of molecular sciences · 2026Review
- 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
- Strengthening Medial Olivocochlear Feedback Reduces the Developmental Impact of Early Noise Exposure.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Strengthening Medial Olivocochlear Feedback Reduces the Developmental Impact of Early Noise Exposure.bioRxiv : the preprint server for biology · 2025Article
- Virally mediated enhancement of efferent inhibition reduces acoustic trauma in wild-type murine cochleas.Molecular therapy. Methods & clinical development · 2025Article
- Impact of a Cancer-Associated Mutation on Poly(ADP-ribose) Polymerase1 Inhibition.The journal of physical chemistry. B · 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
- Lateral olivocochlear neurons modulate cochlear responses to noise exposure.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Key role of the TM2-TM3 loop in calcium potentiation of the α9α10 nicotinic acetylcholine receptor.Cellular and molecular life sciences : CMLS · 2024Article
- Auditory brainstem responses are resistant to pharmacological modulation in Sprague Dawley wild-type and Neurexin1α knockout rats.BMC neuroscience · 2024Article
- Cholinergic modulation in the vertebrate auditory pathway.Frontiers in cellular neuroscience · 2024Review
- Age-related alterations in efferent medial olivocochlear-outer hair cell and primary auditory ribbon synapses in CBA/J mice.Frontiers in cellular neuroscience · 2024Article
- Genetic tools for studying cochlear inhibition.Frontiers in cellular neuroscience · 2024Review
- Molecular earplugs to protect the inner ear.Molecular therapy. Methods & clinical development · 2023Article
- Engineering olivocochlear inhibition to reduce acoustic trauma.Molecular therapy. Methods & clinical development · 2023Article
- Maintained Spatial Learning and Memory Functions in Middle-Aged α9 Nicotinic Receptor Subunit Knock-Out Mice.Brain sciences · 2023Article
- Experience-dependent flexibility in a molecularly diverse central-to-peripheral auditory feedback system.eLife · 2023Article
- Synaptic plasticity of inhibitory synapses onto medial olivocochlear efferent neurons.The Journal of physiology · 2022Article
25 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
The transduction of sound in the auditory periphery, the cochlea, is inhibited by efferent cholinergic neurons projecting from the brainstem and synapsing directly on mechanosensory hair cells. One fundamental question in auditory neuroscience is what role(s) this feedback plays in our ability to hear. In the present study, we have engineered a genetically modified mouse model in which the magnitude and duration of efferent cholinergic effects are increased, and we assess the consequences of this manipulation on cochlear function. We generated the Chrna9L9'T line of knockin mice with a threonine for leucine change (L9'T) at position 9' of the second transmembrane domain of the alpha9 nicotinic cholinergic subunit, rendering alpha9-containing receptors that were hypersensitive to acetylcholine and had slower desensitization kinetics. The Chrna9L9'T allele produced a 3-fold prolongation of efferent synaptic currents in vitro. In vivo, Chrna9L9'T mice had baseline elevation of cochlear thresholds and efferent-mediated inhibition of cochlear responses was dramatically enhanced and lengthened: both effects were reversed by strychnine blockade of the alpha9alpha10 hair cell nicotinic receptor. Importantly, relative to their wild-type littermates, Chrna9(L9'T/L9'T) mice showed less permanent hearing loss following exposure to intense noise. Thus, a point mutation designed to alter alpha9alpha10 receptor gating has provided an animal model in which not only is efferent inhibition more powerful, but also one in which sound-induced hearing loss can be restrained, indicating the ability of efferent feedback to ameliorate sound trauma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.