Effect of selective inner hair cell loss on functional hearing

选择性内毛细胞损失对功能性听力的影响

• 批准号: 8442337
• 负责人: Edward Lobarinas
• 金额: $ 14.16万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-05 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8442337
• 关键词: Acoustic Nerve; Acoustics; Affect; Anatomy; Antineoplastic Agents; Area; Audiometry; Auditory; Auditory Perception; Auditory system; Brain; Carboplatin; Cell physiology; Cells; Chinchilla (genus); Clinical; Cochlea; Cochlear Hearing Loss; Code; Complex; Detection; Discrimination; Fiber; Frequencies; Functional Hearing Loss; Goals; Hearing; Impairment; Inner Hair Cells; Labyrinth; Lead; Location; Masks; Measures; Mechanics; Mediating; Methods; Modeling; Nerve Fibers; Neurons; Neuropathy; Noise; Outer Hair Cells; Output; Pathology; Patients; Pattern; Performance; Physiology; Play; Process; Psychoacoustics; Pure-Tone Audiometry; Rehabilitation therapy; Resolution; Role; Sensory; Signal Transduction; Speech; Speech Perception; Stimulus; Synapses; Testing; Time; Training; behavior test; cell injury; cell type; hearing impairment; indexing; otoacoustic emission; ototoxicity; relating to nervous system; research study; sound; spiral ganglion

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.

描述（由申请人提供）：虽然外毛细胞 (OHC) 在放大内耳机械能方面发挥着主要作用，但内毛细胞 (IHC) 接触 90-95% 的听觉传入纤维，将信息传递给大脑。迄今为止，选择性 IHC 损失对听觉感知的影响尚未得到很好的理解，尽管它们对编码简单和复杂信号（例如语音）很重要。该项目的总体目标是表征和量化选择性 IHC 损失对听力敏感性、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 IHC 和 I 型听觉神经纤维。该提案的目的是使用龙猫模型来识别因 IHC 损失而发生的特定听觉缺陷。目前正在使用针对耳蜗死亡区域的临床测试来确定 IHC 可能不再存在的耳蜗区域。然而，部分 IHC 丧失的程度与功能性听力缺陷之间的关系在很大程度上尚不清楚。临床上，有人认为 IHC 病理学可能在听觉神经病 (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 IHC 损失相关，将训练龙猫执行五项听觉任务，测量听觉感知的不同方面：(1a) 安静时的纯音阈值，以确定听力敏感度，(1b) 纯音阈值 在存在宽带噪声的情况下，评估噪声性能中的信号；(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；以及阈值与持续时间函数的关系，以确定时间总和。在卡铂治疗前后将评估听力行为测试，听力表现的变化将与 IHC 损失程度相关。此外，还将在卡铂治疗前后获得 OHC、畸变产物耳声发射 (DPOAE) 的客观测量结果。我假设 IHC 损坏后基本功能（例如安静时检测音调）不会有什么变化。然而，背景噪声、间隙检测和时间求和下的性能将因 IHC 损失的程度而受到损害。我还假设这些类型的损伤可能会严重影响处理复杂声音（例如语音）的能力。