Effects of Conductive Hearing Loss on Neural Mechanisms of Binaural Hearing

描述（由申请人提供）：发育期间的单侧传导性听力损失（CHL）可导致听觉功能（包括声音定位）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段还不清楚。双耳听力发展的敏感期被假设为适应由于头部和耳廓生长而导致的声学线索位置的变化。虽然可塑性可以允许神经回路校准的线索，它也可以适应不适当的线索，从CHL。目标是了解具有正常听力的动物和从出生起就患有CHL的动物中位置线索和编码它们的电路的同步发展。这项建议的主要重点是研究编码的耳间水平差（ILD）提示声音的位置在成年动物正常的听力和那些有轻度至中度的单侧CHL目前从出生。在特定目标1中，细胞外记录（单单位和多单位）将用于研究下丘中央核（ICC）神经元的单耳和双耳反应特性，ICC是上行听觉通路中的中脑核，接收来自脑干核团的传入输入，最初编码声音位置的线索。这一目标测试的特定假设，ILD敏感的ICC神经元的声学编码能力的变化，以补偿改变ILD线索，结果作为单侧CHL。为了检验这一假设，将测量纯音和噪声刺激的ILD敏感性，并在正常听力提示条件和模拟CHL条件的“虚拟耳塞”条件下测量单耳和双耳刺激的虚拟空间感受野。具体目标2探讨了由于中耳积液（积液）导致的CHL如何影响位置、耳间时间和水平差异以及单耳频谱形状线索的整个声学线索集合。 公共卫生相关性：在婴儿期出现的常见问题，如中耳疾病（渗出性中耳炎或简单的耳部感染），由于相关的传导性听力损失，可能导致双耳听力缺陷，已被证明会导致未来的语言，学习和社交障碍。对哺乳动物双耳听觉通路的基础发育研究将确定双耳系统是否、在何处以及多长时间是“可塑的”，以及它可能从早期缺陷中恢复的时间过程。对正常和异常发展的透彻理解将有助于设计新的更好的方法来识别，预防和治疗早发性听力损失。

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.