4.6 Article

Pathophysiological changes in inner hair cell ribbon synapses in the ageing mammalian cochlea

期刊

JOURNAL OF PHYSIOLOGY-LONDON
卷 598, 期 19, 页码 4339-4355

出版社

WILEY
DOI: 10.1113/JP280018

关键词

age-related hearing loss; auditory brainstem responses; calcium channels; cochlea; exocytosis; inner hair cells; mouse; ribbon synapses

资金

  1. Wellcome Trust [102892/Z/13/Z]
  2. Medical Research Council [MC/UP/1503/2, MR/S002510/1]
  3. MRC [MC_UP_1503/2] Funding Source: UKRI

向作者/读者索取更多资源

Key points Age-related hearing loss (ARHL) is associated with the loss of inner hair cell (IHC) ribbon synapses, lower hearing sensitivity and decreased ability to understand speech, especially in a noisy environment. Little is known about the age-related physiological and morphological changes that occur at ribbon synapses. We show that the differing degrees of ARHL in four selected mouse stains is correlated with the loss of ribbon synapses, being most severe for the strains C57BL/6NTac and C57BL/6J, less so for C57BL/6NTac(Cdh23+)-Repaired and lowest for C3H/HeJ. Despite the loss of ribbon synapses with age, the volume of the remaining ribbons increased and the size and kinetics of Ca2+-dependent exocytosis in IHCs was unaffected, indicating the presence of a previously unknown degree of functional compensation at ribbon synapses. Although the age-related morphological changes at IHC ribbon synapses contribute to the different progression of ARHL, without the observed functional compensation hearing loss could be greater. Mammalian cochlear inner hair cells (IHCs) are specialized sensory receptors able to provide dynamic coding of sound signals. This ability is largely conferred by their ribbon synapses, which tether a large number of vesicles at the IHC's presynaptic active zones, allowing high rates of sustained synaptic transmission onto the afferent fibres. How the physiological and morphological properties of ribbon synapses change with age remains largely unknown. Here, we have investigated the biophysical and morphological properties of IHC ribbon synapses in the ageing cochlea (9-12 kHz region) of four mouse strains commonly used in hearing research: early-onset progressive hearing loss (C57BL/6J and C57BL/6NTac) and 'good hearing' strains (C57BL/6NTac(Cdh23+)and C3H/HeJ). We found that with age, both modiolar and pillar sides of the IHC exhibited a loss of ribbons, but there was an increased volume of those that remained. These morphological changes, which only occurred after 6 months of age, were correlated with the level of hearing loss in the different mouse strains, being most severe for C57BL/6NTac and C57BL/6J, less so for C57BL/6NTac(Cdh23+)and absent for C3H/HeJ strains. Despite the age-related reduction in ribbon number in three of the four strains, the size and kinetics of Ca2+-dependent exocytosis, as well as the replenishment of synaptic vesicles, in IHCs was not affected. The degree of vesicle release at the fewer, but larger, individual remaining ribbon synapses colocalized with the post-synaptic afferent terminals is likely to increase, indicating the presence of a previously unknown degree of functional compensation in the ageing mouse cochlea.

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