Abstract
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/6NTacCdh23+ -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 (9-12kHz 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/6NTacCdh23+ 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 6months 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/6NTacCdh23+ 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.
Highlights
Age-related hearing loss (ARHL) is the most common form of sensory deficit in the human population (Bowl & Dawson, 2019), causing a progressive, bilateral sensorineural loss associated with decreased hearing sensitivity, decreased ability to understand speech and impaired sound localization (Gates & Mills, 2005; Gordon-Salant, 2005)
We investigated whether the different auditory brainstem responses (ABRs) thresholds and wave I among the different mouse strains were due to defects in exocytosis at inner hair cells (IHCs) ribbon synapses with age
We have investigated age-related changes in the biophysical and morphological properties of IHC ribbon synapses in the 9–12 kHz cochlear region of four commonly used mouse strains with different progression of hearing loss (C57BL/6J, C57BL/6NTac, C57BL/6NTacCdh23+ and C3H/HeJ)
Summary
Age-related hearing loss (ARHL) is the most common form of sensory deficit in the human population (Bowl & Dawson, 2019), causing a progressive, bilateral sensorineural loss associated with decreased hearing sensitivity, decreased ability to understand speech and impaired sound localization (Gates & Mills, 2005; Gordon-Salant, 2005). Each postsynaptic type I SGN forms only one synapse with an adult IHC (Pujol et al 1998), with up to ß20 afferent neurons contacting a single IHC in mice (Meyer et al 2009). These SGNs are segregated around the basolateral membrane of IHCs. In the cat, while high-spontaneous-rate (low-threshold) spiral ganglion fibres preferentially contact the pillar side of IHCs (towards the outer hair cells) with small synaptic ribbons, low-spontaneous-rate (high-threshold) fibres primarily contact the modiolar side (towards the cochlear nerve) with larger synaptic ribbons (Liberman, 1978; Liberman et al 1990). Very little is known about how ribbon synapses in mouse IHCs, and their associated afferent connections, change with cochlear ageing, and which of those changes directly influences the temporal acquisition of ARHL
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