Temporary noise-induced hearing loss was long thought to be associated with only temporary damage to the inner ear with no residual loss of function. However, the studies of the last two decades revealed a permanent noise-induced loss of up to 50% of the ribbon synapses of inner hair cells (IHC), followed by the loss of spiral ganglion neurons (SGN) within a time window of several months to over a year (Kujawa and Liberman 2009). Such synaptic damage occurred even in the presence of complete recovery of hearing thresholds. Synapse loss and the associated delayed SGN loss was suggested to be due to excessive glutamate release in response to noise, which causes excitotoxic damage to IHC synapses (Ruel et al. 2007; Kujawa and Liberman 2009, Hu et al. 2020). In our study, a new mouse model of noise-induced synaptopathy was developed using three- to four-week-old mice exposed to noise under isoflurane gas anesthesia. The animals were exposed to two different moderate noise intensities (92 dB and 96 dB for two hours). We used both system physiological measurements by ABR and DPOAE, cell physiological measurements by patch clamp and immunohistochemistry to characterize the effects of noise exposure. We demonstrate a 20-25% reduction in the number of ribbon synapses in the high-frequency regions (≥24 kHz) of the noise-exposed ears at the noise intensities studied (92 dB SPL and 96 dB SPL). Two weeks after noise exposure, patch-clamp recordings from basal IHCs however showed no significant changes in ribbon synapse functionality, despite a moderate but significant decrease in synapse density at high-frequency tonotopic positions. In the future, this model will be used to investigate promising substances for synapse regeneration and the mechanisms of noise-induced synaptopathy.

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