Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
Neurosci Lett. 2019 Aug 10;707:134268. doi: 10.1016/j.neulet.2019.05.022. Epub 2019 May 16.
For decades, studies on noise-induced hearing loss have been focusing on the loss of sensory hair cells and/or auditory afferent fibers following severe noise exposure. Recently, a condition of hidden hearing loss was characterized, in which moderate noise exposure that causes only temporary threshold elevation could induce persistent reduction in auditory brainstem response (ABR) amplitudes and loss of ribbon synapses in inner hair cells (IHCs). However, it is not clear whether and how moderate noise exposure alters the functionality of surviving and/or recovering ribbon synapses in IHCs. To address this issue, we applied moderate noise exposure to mice and combined auditory systems physiology, whole-mount immunofluorescence staining and patch-clamp electrophysiology to characterize changes of ribbon synapse functions in IHCs. After the noise exposure, the ABR threshold was elevated and then recovered, while the ABR Wave I amplitude was reduced but did not recover. Coincidently, whole-mount cochlea staining revealed the loss and recovery of ribbon synapses in IHCs. We then performed whole-cell patch-clamp recording in IHCs and we found that the Ca current, the sustained exocytosis of synaptic vesicles, and the replenishment of synaptic vesicles were all significantly reduced one day after the noise exposure. Fourteen days after the noise exposure, however, only the sustained exocytosis failed to recover, and further examination revealed that this persistent reduction is due to a decrease in the Ca efficiency of triggering exocytosis. In conclusion, our results suggest temporary and persistent alterations of ribbon synapse functions in IHCs contribute to the hidden hearing loss.
几十年来,噪声性听力损失的研究一直集中在严重噪声暴露后感觉毛细胞和/或听觉传入纤维的损失上。最近,人们描述了一种隐蔽性听力损失的情况,即中度噪声暴露只会暂时引起阈值升高,但会导致听觉脑干反应(ABR)幅度的持续降低和内毛细胞(IHC)中连接突触的丢失。然而,目前尚不清楚中度噪声暴露是否以及如何改变 IHC 中存活和/或恢复的连接突触的功能。为了解决这个问题,我们对小鼠进行了中度噪声暴露,并结合听觉系统生理学、全耳蜗免疫荧光染色和膜片钳电生理学来描述 IHC 中连接突触功能的变化。噪声暴露后,ABR 阈值升高,然后恢复,而 ABR 波 I 幅度降低但未恢复。巧合的是,全耳蜗染色显示 IHC 中的连接突触丢失和恢复。然后,我们在 IHC 中进行全细胞膜片钳记录,发现钙电流、突触小泡的持续胞吐作用和突触小泡的补充都在噪声暴露后一天明显减少。然而,14 天后,只有持续的胞吐作用未能恢复,进一步的检查表明,这种持续的减少是由于触发胞吐作用的钙效率降低所致。总之,我们的结果表明,IHC 中连接突触功能的暂时和持续改变导致了隐蔽性听力损失。