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: 8252136
• 负责人: Edward Lobarinas
• 金额: $ 1.23万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 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 2012-08-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8252136
• 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; public health relevance; 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. PUBLIC HEALTH RELEVANCE: The consequences of selective IHC loss on hearing remain poorly understood despite their critical role as these cells synapse with over 90% of afferent auditory nerve fibers that transmit acoustic information to the brain. The overall goal of this project is to determine how auditory sensitivity, hearing in noise and temporal processing is altered when IHC and their afferent connections are damaged in chinchillas treated with the anticancer drug, carboplatin.

描述（由申请人提供）：尽管外毛细胞（OHC）在扩增内耳的机械能量中起着重要作用，但它是内毛细胞（IHC），它与90-95％的听觉传入纤维接触，将信息传入到大脑中。迄今为止，尽管编码简单和复杂的信号（例如语音），但选择性IHC损失对听觉感知的影响尚不清楚。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，噪声听力和时间处理的影响。重要的是，在Chinchilla，Carboplatin，一种抗癌药物，选择性损害IHC和I型听觉神经纤维。该建议的目的是使用龙猫模型来识别随着IHC损失的函数而出现的特定听觉缺陷。目前，用于确定IHC大概不再存在的耳蜗区域的临床测试目前正在用来确定耳蜗的区域。但是，部分IHC丢失的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。在临床上，有人建议IHC病理可以在听觉神经病（AN）或听觉的异常障碍（AD）1中发挥作用1。在存在宽带噪声的情况下，以评估在带通噪声中测量的噪声等噪声和（1C）音调阈值，以确定频率分辨率和关闭频率听力能力，（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功能，以确定时间汇总。在卡铂治疗前后，将评估听力的行为测试，听力表现的变化将与IHC损失程度相关。此外，在卡铂处理之前和之后，将获得OHC的客观度量，失真产物耳声排放（DPOAE）。我假设基本功能，例如在安静中检测音调会在IHC损坏后几乎没有变化。但是，背景噪声，间隙检测和时间求和在IHC损失程度方面将受到损害。我还假设，这些类型的障碍可能会严重影响处理复杂声音（例如语音）的能力。 公共卫生相关性：选择性IHC损失对听力的后果仍然很糟糕，尽管这些细胞与超过90％的传入听觉神经纤维突触，但它们将声学信息传递给大脑。该项目的总体目标是确定当IHC及其传入连接在用抗癌药物Carboplatin处理的龙猫中损坏时，听觉敏感性，听力和时间处理如何改变。