Age differences in perceptual consequences of noise exposure

噪声暴露感知后果的年龄差异

• 批准号: 9914000
• 负责人: MICHEAL L DENT
• 金额: $ 33.59万
• 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 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9914000
• 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; Hyperactive behavior; 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; notch protein; pre-clinical; 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 对于听觉缺陷的发展至关重要，例如言语感知和 嘈杂环境中的声音辨别。一生中接触噪声被认为是 突触病的重要影响因素。在人类中研究这个问题很困难 部分原因是难以确认活人听觉突触的丧失以及有限的 了解生物变量（例如年龄）对噪声引起的突触病的影响。 重要的是，突触病可以在小鼠等动物模型中进行实验研究， 已成为听觉神经科学领域的领先研究工具。总体目标 拟议的实验旨在确定小鼠模型中噪声暴露对年龄的影响 噪声引起的突触病。拟议的研究将应用一系列明确的 在控制良好的突触病小鼠模型中进行心理声学测试。鼠标模型提供 我们有机会筛选年轻或年老时暴露于诱发突触病的动物 除了行为和电生理测量之外，还可以通过噪声来检测功能障碍 进行解剖学测定以确认听神经突触丢失和中枢神经突触丢失的模式 重组。我们将通过三个目标来实现我们的目标： 1) 测量噪声的影响 暴露对年轻和年老小鼠的光谱、时间和强度线索感知的影响； 2） 测量噪声暴露对光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。我们将测试年轻和年老小鼠的突触病相关知觉缺陷 受过训练来检测或区分安静和噪音中的声音。我们的初步数据表明，旧 暴露的小鼠无法像年轻暴露的小鼠一样恢复，我们假设这是 由于老年人大脑的中枢代偿减少。听觉神经突触数量为 对所有小鼠进行量化，以便将行为和生理反应模式关联起来 具有外周突触丢失和中枢重组的模式。实验概述 这里将揭示一套行为测量方法，临床医生可以用它们来揭示 人类患者的突触病，并将确定是否可以优化 ABR 来检测 突触病。