Age differences in perceptual consequences of noise exposure

噪声暴露感知后果的年龄差异

• 批准号: 10392912
• 负责人: MICHEAL L DENT
• 金额: $ 33.54万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-10 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10392912
• 关键词: Acoustic Nerve; Acoustic Trauma; Address; Adult; Affect; Afferent Neurons; Age; Anatomy; Animal Model; Animals; Auditory; Auditory Brainstem Responses; Auditory Perception; Auditory system; Behavioral; Biological; Biological Assay; Biological Factors; Brain; Brain Stem; Cochlea; Cochlear nucleus; Complex; Computer software; Confocal Microscopy; Cues; Data; Dependence; Detection; Development; Discrimination; Elderly; Electrophysiology (science); Environment; Excitatory Synapse; Exhibits; Exposure to; Financial compensation; Frequencies; Functional disorder; Goals; Hair Cells; Health; Hearing; Hearing Tests; Human; Hyperactivity; Image; Immunohistochemistry; Impairment; Inhibitory Synapse; Investigation; Knowledge; Label; Lead; Link; Masks; Measures; Modeling; Mus; Neurosciences; Noise; Noise-Induced Hearing Loss; Outcome; Pathology; Patients; Pattern; Perception; Performance; Peripheral; Physiological; Predisposition; Preventive; Procedures; Process; Psychoacoustics; Recovery; Research; Role; Signal Transduction; Speech Perception; Speech Sound; Stimulus; Synapses; Techniques; Testing; Therapeutic; Time; Training; age difference; age related; base; behavior measurement; behavioral impairment; brain tissue; cohort; experimental study; functional loss; functional outcomes; hearing impairment; mature animal; middle age; mouse model; nerve damage; noise exposure; notch protein; pre-clinical assessment; response; sound; speech in noise; tool; vocalization; young adult

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.

项目概要： 突触病，即毛细胞与其传入神经元之间功能性突触的丧失，被认为是 在听觉缺陷的发展中具有核心重要性，如言语感知和 噪音环境中的声音辨别力。人们认为，在人的一生中， 突触病的一个重要促成因素。在人类中调查这个问题是困难的 部分原因是很难确认人类听觉突触的丧失， 了解生物学变量（如年龄）对噪声诱发的突触病的影响。 重要的是，突触病可以在动物模型如小鼠中进行实验研究， 已经成为听觉神经科学的主要研究工具。的总体目标 提出的实验是在小鼠模型中确定噪声暴露的年龄依赖性效应 噪音引起的突触病。拟议的研究将采用一组定义明确的 在一个良好控制的突触病小鼠模型中进行心理声学测试。小鼠模型提供了 我们有机会筛选动物暴露作为年轻或老年人的突触病变诱导 噪声对行为和电生理测量的影响，以检测功能障碍， 进行解剖分析以确认听觉神经突触丢失和中枢神经系统损伤的模式。 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 暴露对年轻和年老小鼠的光谱、时间和强度线索的感知; 2） 测量噪声暴露对频谱时间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， 听觉脑干我们将在年轻和年老的老鼠身上测试与突触病变相关的知觉缺陷 被训练在安静和嘈杂的环境中探测或辨别声音的。我们的初步数据表明，旧的- 暴露的小鼠不能像暴露于辐射的小鼠一样恢复，我们假设这是因为 这是因为老年人大脑中的中枢补偿功能减弱。听觉神经突触的数量 在所有小鼠中定量，使得行为和生理反应模式可以关联 伴有外周突触缺失和中枢重组概述的实验 这里将揭示一套行为措施，可用于临床医生揭示 突触病，并将确定是否可以优化ABR，以检测 突触病