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.

项目摘要： 被认为 在发展诸如语音感知和 在嘈杂的环境中的声音歧视。一生中的噪音暴露被认为是 突触病的重要因素。对人类的调查很困难 部分原因是难以确认活着的人类和有限的听觉突触丧失 了解生物学变量（例如年龄对噪声引起的突触病）的影响。 重要的是，突触病可以在动物模型（例如小鼠）中进行实验研究，该模型（如小鼠） 已成为听觉神经科学领域的领先研究工具。总体目标 建议的实验是识别小鼠模型中噪声暴露的年龄依赖性影响 噪声引起的突触病。拟议的研究将应用一电动定义的电池 突触性良好的小鼠模型中的心理声学测试。鼠标模型提供 我们有机会筛查以年轻人或老年人暴露于突触性促性诱导的动物的机会 行为和电生理措施上的噪声，以检测功能障碍 进行解剖测定以确认听觉神经突触损失和中央的模式 重组。我们将通过三个目标来追求目标：1）测量噪声的影响 年轻小鼠和老鼠的光谱，时间和强度线索的感知暴露； 2） 测量噪声暴露对光谱复杂刺激感知的影响； 3） 衡量中央增益补偿和突触重组的潜在变化 听觉脑干。我们将测试年轻小鼠和老鼠的突触性相关感知缺陷 经过训练，可以在安静和噪音中检测或区分声音。我们的初步数据表明旧 暴露的小鼠无法恢复和年轻的小鼠，我们假设这是 由于较老的大脑中心补偿减少。听觉神经突触编号将是 在所有小鼠中都量化，以便可以将行为和生理反应模式相关 带有周围突触损失和中央重组的模式。实验概述了 这里将揭示一套行为措施，可以用临床医生来揭示 人类患者的突触病，将确定是否可以优化ABR以检测 突触病。