Biophysical and morphological changes in inner hair cells and their efferent innervation in the ageing mouse cochlea
Jing‐Yi Jeng, Adam J. Carlton, Stuart L. Johnson, Steve D. M. Brown, Matthew C. Holley, Michael R. Bowl, Walter Marcotti
Abstract
Key points Age‐related hearing loss is a progressive hearing loss involving environmental and genetic factors, leading to a decrease in hearing sensitivity, threshold and speech discrimination. We compared age‐related changes in inner hair cells (IHCs) between four mouse strains with different levels of progressive hearing loss. The surface area of apical coil IHCs (9–12 kHz cochlear region) decreases by about 30–40% with age. The number of BK channels progressively decreases with age in the IHCs from most mouse strains, but the basolateral membrane current profile remains unchanged. The mechanoelectrical transducer current is smaller in mice harbouring the hypomorphic Cdh23 allele Cdh23 ahl (C57BL/6J; C57BL/6NTac), but not in Cdh23 ‐repaired mice (C57BL/6NTac Cdh23+ ), indicating that it could contribute to the different progression of hearing loss among mouse strains. The degree of efferent rewiring onto aged IHCs, most likely coming from the lateral olivocochlea fibres, was correlated with hearing loss in the different mouse strains. 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 Cdh23 ahl (C57BL/6J and C57BL/6NTac), from late‐onset hearing loss mice (C3H/HeJ), and from mice corrected for the Cdh23 ahl mutation (C57BL/6NTac Cdh23+ ) 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/6NTac Cdh23+ 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 Cdh23 ahl allele but not in C57BL/6NTac Cdh23+ mice, indicating that the MET apparatus directly contributes to the progression of age‐related hearing loss.