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Auditory-Nerve Responses in Mice with Noise-Induced Cochlear Synaptopathy.

Kirupa Suthakar,M. Liberman

Published 2021 in Journal of Neurophysiology

ABSTRACT

Cochlear synaptopathy is the noise-induced or age-related loss of ribbon synapses between inner hair cells (IHCs) and auditory nerve fibers (ANFs), first reported in CBA/CaJ mice. Recordings from single ANFs in anaesthesized, noise-exposed guinea pigs suggested that neurons with low spontaneous rates (SRs) and high thresholds are more vulnerable than low-threshold, high-SR fibers. However, there is extensive post-exposure regeneration of ANFs in guinea pigs, but not in mice. Here, we exposed CBA/CaJ mice to octave-band noise and recorded sound-evoked and spontaneous activity from single ANFs at least 2 weeks later. Confocal analysis of cochleae immunostained for pre- and post-synaptic markers confirmed the expected loss of 40 - 50% of ANF synapses in the basal half of the cochlea, however, our data were not consistent with a selective loss of low-SR fibers. Rather they suggested a loss of both SR groups in synaptopathic regions. Single-fiber thresholds and frequency tuning recovered to pre-exposure levels however, response to tone bursts showed increased peak and steady-state firing rates as well as decreased jitter in first-spike latencies. This apparent gain-of-function increased the robustness of tone-burst responses in the presence of continuous masking noise. This study suggests that the nature of noise-induced synaptic damage varies between different species and that, in mouse, the noise-induced hyperexcitability seen in central auditory circuits is also observed at the level of the auditory nerve.

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