Dendritic Degeneration and Altered Synaptic Innervation of a Central Auditory Neuron During Age-related Hearing Loss

Abstract

Cellular morphology and synaptic configuration are key determinants of neuronal function and are often modified under pathological conditions. In the first nucleus of the central auditory system, the cochlear nucleus (CN), principal bushy neurons specialize in processing temporal information of sound critical for hearing. These neurons alter their physiological properties during aging that contribute to age-related hearing loss (ARHL). The structural basis of such changes remains unclear, especially age-related modifications in their dendritic morphology and the innervating auditory nerve (AN) synapses. Using young (2-5 months) and aged (28-33 months) CBA/CaJ mice of either sex, we filled individual bushy neurons with fluorescent dye in acute brain slices to characterize their dendritic morphology, followed by immunostaining against vesicular glutamate transporter 1 (VGluT1) and calretinin (CR) to identify innervating AN synapses. We found that dendritic morphology of aged bushy neurons had significantly reduced complexity, suggesting age-dependent dendritic degeneration, especially in neurons with predominantly non-CR-expressing synapses on the soma. These dendrites were innervated by AN bouton synapses, which were predominantly non-CR-expressing in young mice but had increased proportion of CR-expressing synapses in old mice. While somatic AN synapses degenerated substantially with age, as quantified by VGluT1-labeled puncta volume, no significant difference was observed in the total volume of dendritic synapses between young and old mice. Consequently, synaptic density on dendrites was significantly higher in old mice. The findings suggest that dendritic degeneration and altered synaptic innervation in bushy neurons during aging may underlie their changed physiological activity and contribute to the development of ARHL.

Keywords: age-related hearing loss; auditory nerve synapse; bushy neurons; calretinin; cochlear nucleus; dendritic degeneration.