Neural Basis of Hyperacusis

 描述（由申请人提供）：强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输出。奇怪的是，耳蜗损伤往往会在阈上强度下增强中枢听觉通路的神经活动。这种中枢听觉通路的代偿性增加被称为增强的中枢增益。增强的中央增益被认为是负责听觉过敏（响度不耐受）和耳鸣，两个衰弱的条件，折磨数百万美国人。本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噪声暴露引起的听觉过敏和耳鸣。为了实现这一点，我们将确定噪声或药物引起的听觉过敏的时间和频谱特性是否匹配听觉皮层（AC），内侧膝状体（MGB），外侧杏仁核和下丘（IC）中的中枢增益增加的电生理度量的时间过程和频谱特征。我们还将确定噪声诱导或药物诱导的耳鸣的时程是否与听觉过敏的时程和频谱特征以及AC、MGB、LA或IC中的中枢增益增加相关。由于过度兴奋性障碍可以通过调节钾通道通透性的药物来控制，我们将测试钾通道调节剂可以抑制噪声或药物诱导的听觉过敏和增强的中枢增益的假设。拟议的研究旨在增加我们对听觉过敏和耳鸣的神经机制的理解，并测试新的药理学药物治疗这两种衰弱性疾病的疗效。

 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.