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（由申请人提供）：强烈的噪音暴露和耳毒性药物会导致听力损失并减少耳蜗的神经输出，但矛盾的是，耳蜗损伤往往会增强中枢听觉通路的神经活动，这种神经活动会在阈值以上的强度下增强。被称为增强型中央增益 增强型中央增益被认为是导致听觉过敏（响度不耐受）和耳鸣的原因，该项目的目标是通过实验测试中央增益模型，以确定它是否可以解释耳毒性药物或强烈噪音暴露引起的听力过敏和耳鸣。噪声引起或药物引起的听觉过敏的时间和频谱特性与听觉皮层（AC）、内侧膝状体中央增益增加的电生理指标的时间过程和频谱特征相匹配我们还将确定噪声引起或药物引起的耳鸣的时间过程是否与听觉过敏的时间过程和频谱特征以及 AC、MGB 中央增益增加相关。由于过度兴奋性疾病可以通过调节钾通道通透性的药物来控制，因此我们将检验钾通道调节剂可以抑制噪音或药物引起的听觉过敏和增强中枢增益的假设。拟议的研究旨在增加我们对听觉过敏和耳鸣神经机制的理解，并测试新型药物治疗这两种衰弱性疾病的功效。