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）在放大内耳的机械能方面起着主要作用，但将信息传递给大脑的是与90-95%的听觉传入纤维接触的内毛细胞（IHC）。迄今为止，选择性IHC丧失对听觉感知的影响尚未得到很好的理解，尽管它们在编码简单和复杂的信号（如语音）方面都很重要。该项目的总体目标是描述和量化选择性IHC损失对听力敏感性、噪音听力和时间处理的影响。重要的是，在栗鼠中，卡铂，一种抗癌药物，选择性损伤IHC和i型听觉神经纤维。本提案的目的是使用栗鼠模型来识别作为IHC丧失的功能而发生的特定听觉缺陷。临床试验，对于耳蜗死亡区域，目前正在使用，以确定耳蜗的区域，IHC可能不再存在。然而，部分免疫组化损失程度与功能性听力缺陷之间的关系在很大程度上是未知的。临床研究表明，免疫组化病理可能在听神经病变（AN）或听觉不同步（AD）中发挥作用1。为了确定哪些功能缺陷与免疫组化损失有关，龙猫将被训练执行五项听觉任务，这些任务测量听觉感知的不同方面：（1a）安静环境下的纯音阈值，用于确定听力灵敏度；（1b）存在宽带噪声时的纯音阈值，用于评估信号在噪声中的表现；（1c）在带通噪声中测量的音调阈值，用于确定频率分辨率和频外听力能力；（2a）宽带噪声中的间隙检测，用于评估时间敏锐度和阈值与持续时间函数，以确定时间总和。卡铂治疗前后进行听力行为测试，听力表现的变化与IHC损失程度相关。此外，将获得卡铂治疗前后OHC的客观测量，畸变产物耳声发射（DPOAE）。我推测，IHC损伤后，诸如静音音调检测等基本功能几乎没有变化。然而，在背景噪声、间隙检测和时间求和下的性能将受到IHC损失程度的损害。我还假设，这些类型的损伤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.