Effect of selective inner hair cell loss on functional hearing

描述（由申请人提供）：虽然外毛细胞（OHC）在放大内耳中的机械能方面发挥主要作用，但内毛细胞（IHC）接触90-95%的听觉传入纤维，将信息传递到大脑。迄今为止，选择性IHC损失对听觉感知的影响还没有得到很好的理解，尽管它们对简单和复杂信号（如语音）的编码都很重要。该项目的总体目标是表征和量化选择性IHC损失对听力灵敏度，噪声中的听力和时间处理的影响。重要的是，在龙猫中，抗癌药物卡铂会选择性损害免疫组化和I型听觉神经纤维。本提案的目的是使用灰鼠模型来识别特定的听觉缺陷，发生作为一个功能的IHC损失。耳蜗死区的临床测试目前用于确定耳蜗中可能不再存在IHC的区域。然而，部分IHC损失和功能性听力障碍的程度之间的关系在很大程度上是未知的。临床上，已经表明IHC病理学可能在听觉神经病（AN）或听觉不同步（AD）1中发挥作用。为了确定哪些功能缺陷与IHC损失相关，龙猫将被训练执行五项听觉任务，以测量听觉感知的不同方面：（1a）安静时的纯音阈值，以确定听力灵敏度，（1b）在宽带噪声存在下的纯音阈值，以评估噪声中的信号，以及（1c）在带通噪声中测量音调阈值以确定频率分辨率和离频听力能力，（2a）宽带噪声中的间隙检测以评估时间敏锐度和阈值与持续时间函数以确定时间总和。将在卡铂治疗前后评估听力的行为测试，听力表现的变化将与IHC损失的程度相关。此外，还将在卡铂治疗前后获得OHC（畸变产物耳声发射（DPOAE））的客观指标。我假设，基本功能，如检测音调在安静将显示小的变化后，免疫组化损害。然而，在背景噪声、间隙检测和时间求和下的性能将与IHC损失的程度相关地受损。我还假设，这些类型的障碍可能会严重影响处理复杂声音（如语音）的能力。

DESCRIPTION (provided by applicant): Although outer hair cells (OHC) play a major role in amplifying mechanical energy in the inner ear, it is the inner hair cells (IHC), which contact 90-95% of the auditory afferent fibers that relay information to the brain. To date, the effects of selective IHC loss on auditory perception are not well understood despite their importance coding both simple and complex signals such as speech. The overall goal of this project is to characterize and quantify the effects of selective IHC loss on hearing sensitivity, hearing in noise, and temporal processing. Importantly, in the chinchilla, carboplatin, an anticancer drug, selective damages IHC and type-I auditory nerve fibers. The purpose of this proposal is to use the chinchilla model to identify specific auditory deficits that occur as a function of IHC loss. Clinical tests, for cochlear dead regions, are currently in use to determine areas of the cochlea where IHC presumably no longer exist. However, the relationship between the extent of partial IHC loss and functional hearing deficits is largely unknown. Clinically, it has been suggested that IHC pathology could play a role in Auditory Neuropathy (AN) or Auditory Dyssynchrony (AD) 1. To determine what functional deficits are associated with IHC loss, chinchillas will be trained to perform five auditory tasks that measure different aspects of auditory perception: (1a) Pure-tone thresholds in quiet to determine hearing sensitivity, (1b) pure-tone thresholds in the presence of broadband noise to assess signal in noise peformance and (1c) tone thresholds measured in bandpass noise to determine frequency resolution and off frequency hearing ability, (2a) gap detection in broadband noise to assess temporal acuity and threshold versus duration functions to determine temporal summation. Behavioral test of hearing will be assessed before and after carboplatin treatment and changes in hearing performance will be correlated with the degree of IHC loss. In addition, objective measures of OHC, distortion product otoacoustic emissions (DPOAE), will be obtained before and after carboplatin treatment. I hypothesize that basic function such as detection of tones in quiet will show little change after IHC damage. However, performance under background noise, gap detection, and temporal summation will be impaired in relation to the extent of IHC loss. I also hypothesize that these types of impairments could severely impact the ability to process complex sounds such as speech.