Age differences in perceptual consequences of noise exposure

项目总结： 突触病，即毛细胞和它们的传入神经元之间失去功能性突触，被认为 在听觉缺陷的发展中起核心作用，如言语知觉和 嘈杂环境中的声音辨别。生命中的噪音暴露被认为是 这是突触形成的一个重要因素。在人类身上研究这个问题是困难的。 部分原因是很难证实活人和有限的 了解年龄等生物变量对噪声诱导的突触的影响。 重要的是，突触可以在动物模型中进行实验研究，比如小鼠 已经成为听神经科学的领先研究工具。《公约》的总体目标 建议的实验是在小鼠模型中确定噪声暴露的年龄相关效应 噪音引起的突触反应。拟议的研究将应用一系列定义明确的 在控制良好的突触小鼠模型中进行心理声学测试。小鼠模型提供了 美国有机会筛查幼年或年长时接触到突触诱导的动物 行为和电生理措施上的噪声，以检测功能障碍 进行解剖学分析以确认听神经突触丢失和中枢神经的模式 重组。我们将通过三个目标来实现我们的目标：1)测量噪音的影响 暴露于小鼠和老年小鼠对光谱、时间和强度线索的感知；2) 测量噪声暴露对光谱复杂刺激感知的影响；3) 测量中枢增益补偿和突触重组的潜在变化 听觉脑干。我们将测试年轻和老年小鼠与突触相关的知觉缺陷 被训练在安静和嘈杂的环境中探测或辨别声音。我们的初步数据显示旧的- 暴露的小鼠不能像年轻暴露的小鼠那样恢复，我们假设这是 这是由于老年人大脑的中枢补偿减少。听神经突触数量将会是 在所有小鼠中进行量化，以便将行为和生理反应模式相关联 外周突触丢失和中枢重组的模式。概述了这些实验 这里将揭示一套行为测量，临床医生可以使用这些测量方法来揭示 并将确定是否可以优化ABR来检测 突触疗法。

PROJECT SUMMARY: Synaptopathy, loss of functional synapse between hair cells and their afferent neurons, is thought to be of central importance in the development of auditory deficits such as speech perception and sound discrimination in noisy environments. Noise exposure during the lifetime is thought to be an important contributing factor to synaptopathy. Investigation of this problem is difficult in humans in part due to the difficulty confirming loss of auditory synapses in living humans and the limited knowledge of the effects of biological variables such as age on noise-induced synaptopathy. Importantly, synaptopathy can experimentally investigated in animal models such as mice, which have emerged as a leading research tool in auditory neuroscience. The overall objective of the proposed experiments is to identify age-dependent effects of noise exposure in a mouse model of noise-induced synaptopathy. The proposed studies will apply a battery of well-defined psychoacoustic tests in a well-controlled mouse model of synaptopathy. The mouse model affords us the opportunity to screen animals exposed as young or older adults to synaptopathy-inducing noise on behavioral and electrophysiological measures to detect dysfunction in addition to performing anatomical assays to confirm the pattern of auditory nerve synapse loss and central reorganization. We will pursue our objective through three aims: 1) Measure the effects of noise exposure on the perception of spectral, temporal, and intensity cues in young and old mice; 2) Measure the effects of noise exposure on the perception of spectrotemporally complex stimuli; 3) Measure central gain compensation and the underlying changes in synaptic reorganization in the auditory brainstem. We will test for synaptopathy-related perceptual deficits in young and old mice trained to detect or discriminate sounds in quiet and noise. Our preliminary data indicate that old- exposed mice cannot recover as well as younger-exposed mice, and we hypothesize that this is due to reduced central compensation in the older brain. Auditory nerve synapse numbers will be quantified in all mice so that behavioral and physiological response patterns can be correlated with patterns of peripheral synapse loss and central reorganization. The experiments outlined here will reveal a suite of behavioral measures that can be used by clinicians to reveal synaptopathy in human patients and will identify whether or not ABRs can be optimized to detect synaptopathy.