Conrad, L.J., Grandi, F.C. orcid.org/0000-0002-1303-6710, Carlton, A.J. et al. (6 more authors) (2024) The upregulation of K+ and HCN channels in developing spiral ganglion neurons is mediated by cochlear inner hair cells. The Journal of Physiology, 602 (20). pp. 5329-5351. ISSN 0022-3751
Abstract
Spiral ganglion neurons (SGNs) are primary sensory afferent neurons that relay acoustic information from the cochlear inner hair cells (IHCs) to the brainstem. The response properties of different SGNs diverge to represent a wide range of sound intensities in an action-potential code. This biophysical heterogeneity is established during pre-hearing stages of development, a time when IHCs fire spontaneous Ca2+ action potentials that drive glutamate release from their ribbon synapses onto the SGN terminals. The role of spontaneous IHC activity in the refinement of SGN characteristics is still largely unknown. Using pre-hearing otoferlin knockout mice (Otof−/−), in which Ca2+-dependent exocytosis in IHCs is abolished, we found that developing SGNs fail to upregulate low-voltage-activated K+-channels and hyperpolarisation-activated cyclic-nucleotide-gated channels. This delayed maturation resulted in hyperexcitable SGNs with immature firing characteristics. We have also shown that SGNs that synapse with the pillar side of the IHCs selectively express a resurgent K+ current, highlighting a novel biophysical marker for these neurons. RNA-sequencing showed that several K+ channels are downregulated in Otof−/− mice, further supporting the electrophysiological recordings. Our data demonstrate that spontaneous Ca2+-dependent activity in pre-hearing IHCs regulates some of the key biophysical and molecular features of the developing SGNs.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/ |
Keywords: | afferent fibres; cochlea; development; inner hair cells; potassium currents; spiral ganglion neurons |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 30 Sep 2024 13:42 |
Last Modified: | 25 Feb 2025 15:45 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1113/jp286134 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:217748 |