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.