Cochlear Ribbon Synapses in Aged Gerbils

Abstract

In mammalian hearing, type-I afferent auditory nerve fibers comprise the basis of the afferent auditory pathway. They are connected to inner hair cells of the cochlea via specialized ribbon synapses. Auditory nerve fibers of different physiological types differ subtly in their synaptic location and morphology. Low-spontaneous-rate auditory nerve fibers typically connect on the modiolar side of the inner hair cell, while high-spontaneous-rate fibers are typically found on the pillar side. In aging and noise-damaged ears, this fine-tuned balance between auditory nerve fiber populations can be disrupted and the functional consequences are currently unclear. Here, using immunofluorescent labeling of presynaptic ribbons and postsynaptic glutamate receptor patches, we investigated changes in synaptic morphology at three different tonotopic locations along the cochlea of aging gerbils compared to those of young adults. Quiet-aged gerbils showed about 20% loss of afferent ribbon synapses. While the loss was random at apical, low-frequency cochlear locations, at the basal, high-frequency location it almost exclusively affected the modiolar-located synapses. The subtle differences in volumes of pre- and postsynaptic elements located on the inner hair cell’s modiolar versus pillar side were unaffected by age. This is consistent with known physiology and suggests a predominant, age-related loss in the low-spontaneous-rate auditory nerve population in the cochlear base, but not the apex.

Age-related changes in olivocochlear efferent innervation in gerbils

“…We did not investigate the age-related loss of afferents for the sample reported here. However, the loss of afferent synaptic connections was recently quantified for the same tonotopic locations in other samples from our gerbil colony ( Steenken et al, 2021 ; Bovee et al, 2024 ). The implications of this for the novel results reported here will therefore be addressed in the discussion.…”

“…Gerbils are typically classified as “old” when they reach 36 months of age, which corresponds to 50% of their maximal lifespan potential, comparable to a human aged 61 years (reviewed by Castaño-González et al, 2024 ). Age-related morphological changes in the gerbil cochlea include loss of afferent synapses on inner hair cells (IHC; Gleich et al, 2016 ; Steenken et al, 2021 ; Bovee et al, 2024 ), loss of spiral ganglion neurons ( Keithley et al, 1989 ; Suryadevara et al, 2001 ), hair-cell loss ( Tarnowski et al, 1991 ; Adams and Schulte, 1997 ), and a lowered endocochlear potential ( Schulte and Schmiedt, 1992 ; Schmiedt et al, 2002 ). Age-related changes to the efferent innervation of the gerbil cochlea have only been explored in a developmental context ( Rontal and Echteler, 2003 ; Kaiser et al, 2011 ).…”

The Stria Vascularis: Renewed Attention on a Key Player in Age-Related Hearing Loss

“…In contrast, quiet-aged gerbils, with minimal noise exposure throughout their lifespan, consistently show only minimal inner and outer hair cell loss [25,26], in accordance with predominantly metabolic presbycusis. Synaptopathy, or the loss of auditory nerve fibers on the inner hair cells, does occur in quiet-aged gerbils [27][28][29], However, not to such an extent that it necessarily affects hearing thresholds [30][31][32]. Despite reduced acoustic exposure in quiet-aged gerbils, significant HL can still occur, providing an excellent chance to investigate the effects of strial dysfunction [33].…”