Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts 02114, Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114-3096, and Harvard Program in Speech and Hearing Bioscience and Technology, Boston, Massachusetts 02114.
J Neurosci. 2014 Mar 26;34(13):4599-607. doi: 10.1523/JNEUROSCI.4923-13.2014.
The inner ear receives two types of efferent feedback from the brainstem: one pathway provides gain control on outer hair cells' contribution to cochlear amplification, and the other modulates the excitability of the cochlear nerve. Although efferent feedback can protect hair cells from acoustic injury and thereby minimize noise-induced permanent threshold shifts, most prior studies focused on high-intensity exposures (>100 dB SPL). Here, we show that efferents are essential for long-term maintenance of cochlear function in mice aged 1 year post-de-efferentation without purposeful acoustic overexposure. Cochlear de-efferentation was achieved by surgical lesion of efferent pathways in the brainstem and was assessed by quantitative analysis of immunostained efferent terminals in outer and inner hair cell areas. The resultant loss of efferent feedback accelerated the age-related amplitude reduction in cochlear neural responses, as seen in auditory brainstem responses, and increased the loss of synapses between hair cells and the terminals of cochlear nerve fibers, as seen in confocal analysis of the organ of Corti immunostained for presynaptic and postsynaptic markers. This type of neuropathy, also seen after moderate noise exposure, has been termed "hidden hearing loss", because it does not affect thresholds, but can be seen in the suprathreshold amplitudes of cochlear neural responses, and likely causes problems with hearing in a noisy environment, a classic symptom of age-related hearing loss in humans. Since efferent reflex strength varies among individuals and can be measured noninvasively, a weak reflex may be an important risk factor, and prognostic indicator, for age-related hearing impairment.
一种途径对毛细胞对外耳放大的贡献提供增益控制，另一种途径调节耳蜗神经的兴奋性。虽然传出反馈可以保护毛细胞免受声损伤，从而最大限度地减少噪声引起的永久性阈移，但大多数先前的研究都集中在高强度暴露（>100 dB SPL）上。在这里，我们表明，在外周和内毛细胞区域的免疫染色传出末端的定量分析中，在去传出后 1 年没有故意过度暴露于声刺激的情况下，传出对于维持小鼠耳蜗功能是必不可少的。传出神经通路的手术损伤实现了耳蜗去传出，并通过定量分析传出末端的免疫染色进行了评估。传出反馈的丧失加速了年龄相关的耳蜗神经反应幅度的降低，如听脑干反应所见，并增加了毛细胞和耳蜗神经纤维末梢之间突触的丧失，如共聚焦分析耳蜗毛细胞的突触前和突触后标志物的免疫染色所见。这种神经病变也见于中度噪声暴露后，被称为“隐性听力损失”，因为它不影响阈值，但可以在耳蜗神经反应的超阈值幅度中看到，并且可能导致嘈杂环境中的听力问题，这是人类与年龄相关的听力损失的典型症状。由于传出反射强度在个体之间有所不同，并且可以进行非侵入性测量，因此反射较弱可能是与年龄相关的听力障碍的一个重要风险因素和预后指标。
