Sleep immediately after noise overexposure worsens tinnitus in mice

Subjective tinnitus is the most common auditory phantom perception in the absence of an acoustic stimulus yet there is no cure nor widely effective treatment to date. Previously, we suggested that sleep may contribute to tinnitus development after a triggering event, such as noise overexposure (NOE). Here, we investigated the effect of natural sleep on tinnitus development following NOE in mice. One group of mice was kept awake for 6 hours immediately after NOE, whereas a control group could sleep ad libitum. Tinnitus and hearing loss were assessed before and after NOE by determining gap prepulse inhibition of the acoustic startle reflex (GPIAS) and by recording auditory brainstem responses (ABRs). Only mice that were allowed to sleep in the first six hours after NOE developed a significant change in the GPIAS ratio one week after NOE, indicative of tinnitus. Habituation to the startle stimulus was largely similar between both groups, except that at eight weeks after NOE, when GPIAS ratio had returned to baseline levels in both groups, the sleep deprived group showed less habituation to the startle stimulus. Notably, animals in neither group showed significantly elevated ABR thresholds after NOE, yet the control group showed signs of elevated evoked activity in the auditory brainstem one week after NOE. These findings demonstrate that sleep early after noise overexposure may amplify subsequent tinnitus development. Our results suggest that sleep represents a temporal window that may be harnessed for potential modulation or mitigation of noise-induced hearing loss and tinnitus-related impairments.