Neural Basis of Hyperacusis

听觉过敏的神经基础

• 批准号: 9180694
• 负责人: RICHARD J SALVI
• 金额: $ 40.42万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9180694
• 关键词: Affect; American; Amygdaloid structure; Animals; Anti-Anxiety Agents; Anxiety; Auditory area; Auditory system; Behavior; Behavioral; Chronic; Clinical Trials; Cochlea; Data; Disease; Drug Controls; Electrophysiology (science); Frequencies; Goals; Hearing; Hyperactive behavior; Hyperacusis; Implanted Electrodes; Individual; Inferior Colliculus; Lateral; Light; Loudness; Measures; Medial geniculate body; Modeling; Noise; Noise-Induced Hearing Loss; Output; Patients; Permeability; Pharmaceutical Preparations; Pharmacology; Play; Potassium Channel; Property; Rattus; Risk; Risk Factors; Role; Structure; Surveys; Testing; Time; Tinnitus; auditory pathway; behavior measurement; behavior test; cofactor; design; efficacy testing; experimental study; hearing impairment; neuromechanism; novel; ototoxicity; public health relevance; relating to nervous system; sound

 DESCRIPTION (provided by applicant): Intense noise exposure and ototoxic drugs cause hearing loss and reduce the neural output of the cochlea. Paradoxically, cochlear damage often enhances neural activity in the central auditory pathway at suprathreshold intensities. This compensatory increase in the central auditory pathway is referred to as Enhanced Central Gain. Enhanced Central Gain is believed to be responsible for hyperacusis (loudness intolerance) and tinnitus, two debilitating conditions that afflict millions of Americans. The goal of this project s to experimentally test the Central Gain model to determine if it can account for hyperacusis and tinnitus induced by ototoxic drugs or intense noise exposure. To accomplish this, we will determine if the temporal and spectral properties of noise-induced or drug-induced hyperacusis match time course and spectral features of the electrophysiological metric of increased central gain in auditory cortex (AC), medial geniculate body (MGB), lateral amygdala and inferior colliculus (IC). We will also determine if the time course of noise-induced or drug- induced tinnitus is correlated with the time course and spectral features of hyperacusis and increased central gain in the AC, MGB, LA or IC. Since hyperexcitability disorders can be controlled by drugs that regulate potassium channel permeability, we will test the hypothesis that potassium channel modulators can suppress noise- or drug-induced hyperacusis and enhanced central gain. The proposed studies are designed to increase our understanding of the neural mechanisms of hyperacusis and tinnitus and test the efficacy of novel pharmacological agents to treat these two debilitating disorders.

 描述（由适用提供）：强烈的噪声暴露和耳毒性药物会导致听力损失并减少耳蜗的神经元输出。矛盾的是，人工耳蜗损害通常会增强跨牙座强度的中央听觉途径中的神经元活性。中央听觉途径的这种补偿性增加称为中央收益增强。据信，增强的中心收益是造成超气（响度intlerance）和耳鸣的原因，这是两种使人衰弱的条件，使数百万美国人受苦。该项目S的目标是通过实验测试中心增益模型，以确定它是否可以解释耳毒性药物引起的高气囊和耳鸣或强烈的噪声暴露。为此，我们将确定噪声诱导的或药物诱导的超值匹配时间课程以及电生理指标的光谱特征的临时和光谱特性是否是否与噪声诱导或药物诱导的耳鸣的时间过程是否与AC，MGB，MGB，MGB，MGB，MGB，MGB，MGB，MGB，MGB，MGB，MGB，MGB，MGB，MGB，MGB，MGB，MGB，MGB，MGB，MGB，MGB，MGB，MGB，MGB，MGB，MGB，MGB，MGB，IC。由于过度刺激性疾病可以通过调节钾通道渗透率的药物来控制，因此我们将测试以下假设：钾通道调节剂可以抑制噪声或药物诱导的超源症并增强中央增益。拟议的研究旨在提高我们对Hyper Acusis和耳鸣的神经机制的理解，并测试新型药理学剂治疗这两种令人衰弱的疾病的有效性。