Cochlear Synaptopathy: Prevalence, Diagnosis and Functional Consequences

整体项目总结 对噪音和年龄相关听力损失的动物研究的新见解表明， 内耳中最脆弱的元素是毛细胞和感觉之间的突触连接 神经元。这种初级神经变性，也被称为耳蜗性突触，不会升高 阈值。因此，它可以在毛细胞群体完好和听力图正常的耳朵中广泛传播， 在那里它被称为“隐匿性”听力损失。这可能会造成理解演讲的困难 在嘈杂的环境中，并可能是耳鸣和听力亢进的诱因。 耳蜗性突触病变也可能在获得性感音神经性聋中广泛存在 毛细胞损伤的原因和程度。因此，它可能是众所周知的 具有相同“显性”听力测听模式的人的听觉表现差异 损失。 我们的研究中心旨在将这些范式转换的想法从动物模型转移到人类身上 研究对象。基于对显性听力和隐性听力研究的多条研究线索的综合 我们设计了一套生理、电生理和心理物理听力测试 以及我们认为在耳蜗病的诊断和理解中最强大的耳蜗功能 人类受试者的突触。在项目1中，我们将这个测试电池应用于暴露在噪音或 并通过直接测量耳蜗底来测试它们的诊断能力 显性或隐性听力损失病例的组织病理学。在项目2中，我们使用免疫染色直接 评估临床或临床表现为耳蜗性突触的受试者在人的颞骨中耳蜗性突触的发生率 隐匿性听力损失的原因有很多。在项目3中，我们研究了大学中的隐性听力损失 学生通过将测试电池应用于听力图正常但报告范围广泛的受试者 和测量的声音暴露。在项目4中，我们通过以下方式评估患有明显听力损失的老年人 将测试应用于具有仔细匹配的下坡听力图的受试者池中，并通过 表征基于训练的噪声中语音性能的改进，反映在不同的 外周、脑干、中脑和皮质水平。 我们对年轻人的初步研究显示，在一组患有 反复接触高水平音乐，表明这种现象对公众的重要性 健康。以神经营养素为基础的治疗耳蜗性突触病变的成功 动物模型表明，治疗方法可能即将出现。因此，需要更好地理解 对耳蜗性突触病的流行、诊断和功能后果的认识是明确的。

Overall Project Summary New insights from animal studies of noise-induced and age-related hearing loss suggest that the most vulnerable elements in the inner ear are the synaptic connections between hair cells and sensory neurons. This primary neural degeneration, also called cochlear synaptopathy, does not elevate thresholds. Thus, it can be widespread in ears with intact hair cell populations and normal audiograms, where it has been called “hidden” hearing loss. It likely contributes to difficulties understanding speech in a noisy environment and may be an instigating factor in the generation of tinnitus and hyperacusis. Cochlear synaptopathy may also be widespread in acquired sensorineural hearing loss of other etiologies and degrees of hair cell damage. Thus, it may be a major contributor to the well-known differences in auditory performance among people with identical audiometric patterns of “overt” hearing loss. Our Research Center aims to take these paradigm-shifting ideas from animal models to human subjects. Based on the synthesis of many research threads from the study of overt and hidden hearing loss, we have devised a set of physiological, electrophysiological and psychophysical tests of hearing and cochlear function that we believe are most powerful in the diagnosis and understanding of cochlear synaptopathy in human subjects. In Project 1, we apply this test battery to gerbils exposed to noise or ototoxic drugs and test their diagnostic power by directly measuring the underlying cochlear histopathology in cases of overt or hidden hearing loss. In Project 2, we use immunostaining to directly assess the prevalence of cochlear synaptopathy in human temporal bones from subjects with overt or hidden hearing loss with a range of etiologies. In Project 3, we study hidden hearing loss in college students by applying the test battery to subjects with normal audiograms but a broad range of reported and measured sound exposures. In Project 4, we assess older adults with overt hearing loss by applying the tests to a subject pool with carefully matched down-sloping audiograms and by characterizing training-based improvements in speech-in-noise performance as reflected at different peripheral, brainstem, midbrain and cortical levels. Our preliminary studies of young adults show clear signs of hidden hearing loss in a group with repeated exposure to high-level music, suggesting the importance of this phenomenon to the public health. The success of neurotrophin-based approaches to the treatment of cochlear synaptopathy in animal models suggests that therapies may be on the horizon. Thus, the need for better understanding of the prevalence, diagnosis and functional consequences of cochlear synaptopathy is clear.