Jeng, J-Y;
Carlton, A;
Johnson, SL;
Brown, SDM;
Holley, MC;
Bowl, MR;
Marcotti, W;
(2020)
Biophysical and morphological changes in inner hair cells and their efferent innervation in the ageing mouse cochlea.
The Journal of Physiology
, 599
(1)
pp. 269-287.
10.1113/JP280256.
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Abstract
Inner hair cells (IHCs) are the primary sensory receptors of the mammalian cochlea, transducing acoustic information into electrical signals that are relayed to the afferent neurons. Functional changes in IHCs are a potential cause of age‐related hearing loss. Here, we have investigated the functional characteristics of IHCs from early‐onset hearing loss mice harbouring the allele Cdh23ahl (C57BL/6J and C57BL/6NTac), from late‐onset hearing loss mice (C3H/HeJ), and from mice corrected for the Cdh23ahl mutation (C57BL/6NTacCdh23+) with an intermediate hearing phenotype. There was no significant loss of IHCs in the 9–12 kHz cochlear region up to at least 15 months of age, but their surface area decreased progressively by 30–40% starting from ∼6 months of age. Although the size of the BK current decreased with age, IHCs retained a normal KCNQ4 current and resting membrane potential. These basolateral membrane changes were most severe for C57BL/6J and C57BL/6NTac, less so for C57BL/6NTacCdh23+ and minimal or absent in C3H/HeJ mice. We also found that lateral olivocochlear (LOC) efferent fibres re‐form functional axon‐somatic connections with aged IHCs, but this was seen only sporadically in C3H/HeJ mice. The efferent post‐synaptic SK2 channels appear prior to the establishment of the efferent contacts, suggesting that IHCs may play a direct role in re‐establishing the LOC‐IHC synapses. Finally, we showed that the size of the mechanoelectrical transducer (MET) current from IHCs decreased significantly with age in mice harbouring the Cdh23ahl allele but not in C57BL/6NTacCdh23+mice, indicating that the MET apparatus directly contributes to the progression of age‐related hearing loss.
| Type: | Article |
|---|---|
| Title: | Biophysical and morphological changes in inner hair cells and their efferent innervation in the ageing mouse cochlea |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1113/JP280256 |
| Publisher version: | https://doi.org/10.1113/JP280256 |
| Language: | English |
| Additional information: | This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Auditory brainstem responses; C3H/HeJ mice; C57BL/6 mice; cadherin 23; cochlea; hair cells; hearing loss; mechanoelectrical transduction; olivocochlear efferent fibres; potassium currents |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > The Ear Institute |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10115148 |
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