Repeated Moderate Sound Exposure Causes Accumulated Trauma to Cochlear Ribbon Synapses in Mice

Repeated induction of a temporary threshold shift (TTS) may result in a permanent threshold shift (PTS) and is thought to be associated with early onset of age-related hearing loss (ARHL). The possibility that a PTS might be induced by administration of repeated TTS-inducing noise exposures (NEs) over a short period during early adulthood has not been formally investigated. We aimed to investigate possible cumulative acoustic overstimulation effects that permanently shift the auditory threshold. Young adult C57BL/6J mice were exposed twice to moderate white noise in an experimental design that minimized the effects of aging. The first exposure resulted in a reversible noise-induced hearing loss (NIHL) measured as recoverable alterations in auditory brainstem response (ABR) thresholds, waveform amplitudes, and numbers of ribbon synapses. The second NE with the same parameters caused persistent threshold shifts, wave I amplitude reductions, wave IV/I ratio enhancements, and synaptic losses, even though recovery time sufficient for a TTS had been provided. The pattern of PTS resembled NIHL since the observed impairments tonotopically followed the power spectrum of the noise insult, rather than ARHL, which distributes at higher frequencies. No significant changes were observed in the control group as the mice aged. To conclude, our results demonstrate a cumulative effect of repetitive TTS-inducing NE on hearing function and synaptic plasticity that does not cause premature ARHL, thereby providing insight into the pathophysiological mechanisms underlying NIHL and ARHL.