Biophysical and morphological changes in inner hair cells and their efferent innervation in the ageing mouse cochlea.

Jing‐Yi Jeng,Michael R Bowl,Stuart L Johnson,Steve D M Brown,Matthew C Holley,Walter Marcotti,Adam J Carlton

doi:10.1113/jp280256

Jing‐Yi Jeng, Michael R Bowl + Show 5 more

Open Access

https://doi.org/10.1113/jp280256

Copy DOI

Abstract

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 (9-12kHz 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 Cdh23ahl (C57BL/6J; C57BL/6NTac), but not in Cdh23-repaired mice (C57BL/6NTacCdh23+ ), 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. 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 9-12kHz cochlear region up to at least 15months of age, but their surface area decreased progressively by 30-40% starting from ∼6months 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.

Highlights

Age-related hearing loss (ARHL), known as presbycusis, is a chronic disorder in which patients suffer from progressive loss of hearing sensitivity and the ability to understand speech with age
We discovered that the mechanoelectrical transducer (MET) current in aged Inner hair cells (IHCs) was differentially affected between C57BL/6NTac and C57BL/6NTacCdh23+ mice, suggesting that it may be involved in the progression of ARHL
We have recently shown that defects in mechanoelectrical transduction in adult IHCs leads to rewiring of the cochlear efferent system (Corns et al 2018), similar to that observed in the ageing cochlea (Lauer et al 2012; Zachary & Fuchs 2015)

Summary

Introduction

Age-related hearing loss (ARHL), known as presbycusis, is a chronic disorder in which patients suffer from progressive loss of hearing sensitivity and the ability to understand speech with age. It is one of the most common forms of hearing loss in adults over 60 years old (Bowl & Dawson, 2019). The depolarizing MET current, which is mainly carried by K+ and by Ca2+ ions, generates a receptor potential that modulates the release of glutamate from IHC ribbon synapses onto the spiral ganglion afferent terminals (Marcotti, 2012; Johnson et al 2019). Recent studies have shown that in ∼1-year-old cochleae of C57BL/6J mice the efferent system undergoes major rewiring, with the reappearance of direct axo-somatic efferent synapses onto aged IHCs (Lauer et al 2012; Zachary & Fuchs 2015) that are normally present only during the pre-hearing stages of development (Glowatzki & Fuchs 2000)

Methods

Results

Conclusion