Effects of Conductive Hearing Loss on Neural Mechanisms of Binaural Hearing

描述（由申请人提供）：发育过程中的单侧传导性听力损失（CHL）可导致包括声音定位在内的听觉功能的长期缺陷。造成这些缺陷的解剖和生理机制以及这些缺陷发生的时间尚不清楚。双耳听力发展的一个敏感时期被假设为适应由于头部和耳廓生长而引起的声音线索的位置变化。虽然可塑性可能允许神经回路根据提示进行校准，但它也可能适应由CHL引起的不适当提示。目的是了解在听力正常的动物和从出生就患有CHL的动物中，定位线索和编码它们的回路的同步发展。本研究的主要重点是研究听力正常的成年动物和出生时患有轻度至中度单侧CHL的成年动物的耳间水平差（ILD）提示声音定位的编码。在具体目标1中，细胞外记录（包括单单元和多单元）将用于研究下丘中央核（ICC）神经元的单耳和双耳反应特性，下丘中央核是上升听觉通路中的中脑核，接收来自脑干核的传入输入，脑干核最初编码声音位置的线索。本研究的目的是验证一个特定的假设，即ILD敏感的ICC神经元的声音编码能力会发生变化，以补偿单侧CHL导致的ILD信号改变。为了验证这一假设，将测量纯音和噪声刺激下的ILD灵敏度，并在正常听力提示条件和模拟CHL的“虚拟耳塞”条件下测量单耳和双耳刺激下的虚拟空间感受野。具体目标2探讨了中耳液体积聚（积液）引起的CHL如何影响声学线索的整体集合，包括位置、耳间时间和水平差异以及单耳频谱形状线索。

DESCRIPTION (provided by applicant): Unilateral conductive hearing loss (CHL) during development can produce long-term deficits in auditory functions including sound localization. The anatomical and physiological mechanisms responsible for and the time period over which these deficits occur are not well understood. A sensitive period for the development of binaural hearing is hypothesized to accommodate changes in the acoustical cues to location due to head and pinnae growth. While plasticity may allow calibration of neural circuits to the cues, it may also adapt to inappropriate cues resulting from CHL. The goals are to understand the concurrent development of the cues to location and the circuits that encode them in animals with normal hearing and those reared from birth with CHL. The primary focus of this proposal is to study the encoding of the interaural level difference (ILD) cue to sound location in adult animals with normal hearing and those that have had a mild to moderate unilateral CHL present from birth. In Specific Aim 1, extracellular recordings (both single- and multi-unit) will be used to study the monaural and binaural response properties of neurons in the central nucleus of the inferior colliculus (ICC), a midbrain nucleus in the ascending auditory pathway that receives afferent inputs from the brainstem nuclei that initially encode the cues to sound location. This aim tests the specific hypothesis that the acoustic coding capabilities of ILD-sensitive ICC neurons change in order to compensate for the altered ILD cues that result as a consequence of the unilateral CHL. To test this hypothesis, ILD sensitivity will be measured for pure-tone and noise stimuli and virtual space receptive fields will be measured for monaural and binaural stimulation under both normal hearing cue conditions and a "virtual earplug" condition that simulates those due to CHL. Specific Aim 2 explores how CHL due to fluid buildup in the middle ear (effusion) affects the entire ensemble of acoustic cues to location, the interaural time and level differences and the monaural spectral shape cues. PUBLIC HEALTH RELEVANCE: Common problems that arise during infancy such as middle ear disease (otitis media with effusion, or simply ear infections) can lead to deficits in binaural hearing, due to the associated conductive hearing losses, that have been shown to lead to future language, learning, and social disabilities. Basic developmental studies of the mammalian binaural auditory pathway will determine if, where, and how long the binaural system is "plastic" and the time course over which it may recover from early deficits. A thorough understanding of normal and abnormal development will facilitate the design of new and better ways to identify, prevent, and possibly to treat early-onset hearing loss.