Hidden Hearing Loss: A View from the Brain

摘要 隐蔽性听力损失的概念挑战了临时性阈值漂移(TTS)反映恢复的观点 恢复正常听力。最近的研究表明，在噪声暴露后会产生TTS，因此在临床上 尽管听力图“正常”，但听神经纤维(ANF)突触仍有永久性损害 耳蜗内毛细胞。隐性听力损失是一个潜在的主要健康问题，因为人类的颞骨和 ABR研究表明，这在人类中很常见。人类临床上剩余的知觉缺陷 正常的听力图反映出时间编码问题，可能是由于失去了高阈值、低自发 对在TTS后优先受影响的ANF进行评级。高阈值ANF的主要中心靶点 位于耳蜗核(CN)的小细胞帽(SCC)内。高阈值ANF及其SCC靶点 显示大动态范围和卓越的超阈值调谐和时间编码，这对于 在嘈杂环境中的语音感知。鳞状细胞癌在人类CN中占有很大比例，并且是 因此有望在隐性听力损失的中枢机制中发挥重要作用。SCC也是独一无二的 内侧橄榄耳蜗区(MOC)神经元的假定受体和投射区。对此的总体假设是 建议SCC在超阈值声音编码中起主要作用，并且这种编码是高度 容易因隐性听力损失而退化。这一系列研究的目的是阐明耳蜗-- 在正常和噪声损伤的隐匿性听力损失动物中，使用最先进的SCC-MOC电路 光遗传学、多通道单单位生理学、轨迹追踪和复杂的免疫组织化学 方法：研究方法。

Abstract The concept of “hidden” hearing loss challenges the idea that temporary threshold shifts (TTS) reflect a return to normal hearing. Recent studies indicate that after noise-exposure that produces TTS, and thus clinically 'normal' audiograms, there is nonetheless permanent damage to auditory nerve fiber (ANF) synapses with cochlear inner hair cells. Hidden hearing loss is a potential major health issue, as human temporal bone and ABR studies suggest it is common in humans. The remaining perceptual deficits in humans with clinically normal audiograms reflect temporal coding problems likely due to loss of the high threshold, low spontaneous rate ANFs, which are preferentially affected after TTS. The primary central targets of high-threshold ANFs reside in the small cell cap (SCC) of the cochlear nucleus (CN). High-threshold ANFs and their SCC targets display large dynamic ranges and superior suprathreshold tuning and temporal coding, which are essential for speech perception in noisy environments. The SCC occupies a large proportion of the CN in humans and is therefore poised to play a major role in central mechanisms of hidden hearing loss. The SCC is unique also as a putative recipient and projection area of medial olivocochlear (MOC) neurons. The overall hypothesis of this proposal is that the SCC plays a major role in suprathreshold sound coding and that this coding is highly susceptible to degradation by hidden hearing loss. The goal of this series of studies is to elucidate the cochlea- SCC-MOC circuit in normal and noise-damaged animals with hidden hearing loss, using state-of-the-art optogenetics, multichannel single unit physiology, tract tracing and sophisticated immunohistochemical methods.