From infra- to ultrasound: Diversity in acoustic processing by the vertebrate ear

描述（由申请人提供）：我们实验室的总体目标是更丰富地了解脊椎动物听觉系统中频率选择性或调谐的结构和生理基础。通过了解动物在其自然栖息地的声学行为，我们提出的研究的主要目标有三个：（1）应用现代技术，为脊椎动物耳中空气传播的声音和基片传播的振动的定位的生理和生物物理机制提供新的见解，（2）了解和理解调节和塑造听觉外周低频选择性的电和机械细胞过程的机制，（3）探索两栖动物耳对超声波具有显著敏感性的生理基础。为了实现这些目标，将进行一系列的四项详细调查，以便（a）直接测量“低频”动物（金鼹鼠）中耳听小骨的运动，以便表征中耳听小骨对空气传播和地震刺激的方向响应-从而将我们的观察扩展到地下地震专家，（B）系统地比较相同毛细胞制剂中的受体药理学和离子电流动力学，以直接测试外源性试剂对低频毛细胞的调谐特性的影响，（c）检查脊椎动物毛细胞中介导响应于细胞外刺激的缓慢运动性的钙-钙调蛋白依赖性收缩机制，以及（d）表征高频专家的外周听觉系统的调谐，并确定辅助该调谐的机制。结果的数据将是丰富的空气传播的声音和基板振动的处理，以及传出介导的反馈在频率调谐的作用的影响。因此，这项工作预计将提供一个框架，了解空气和骨传导的声音传输和调整的动物，包括人类。目前主要的兴趣是传出系统在频率选择性和防止噪声过度刺激的起源中的假定作用。最终，我们的研究可能会导致新的治疗方法来治疗听觉过敏和噪音引起的耳鸣，这两种已知的综合征都涉及传出系统功能障碍。

DESCRIPTION (provided by applicant): The overall goal of our laboratory is a richer understanding of the structural and physiological bases of the frequency selectivity or tuning in the vertebrate auditory system. Driven by a knowledge of the animal's acoustic behavior in its natural habitat, our primary objectives for the proposed research are threefold: (1) to apply modern techniques to provide new insights into the physiological and biophysical mechanisms underlying the localization of airborne sound and substrate-borne vibration in the vertebrate ear, (2) to gain an understanding and appreciation of the mechanisms underlying the electrical and mechanical cellular processes that modulate and sculpt low-frequency selectivity in the auditory periphery, and (3) to explore the physiological bases underlying the newly-discovered remarkable ultrasonic sensitivity in the amphibian ear. To accomplish these objectives, a series of four detailed investigations will be performed in order to (a) directly measure the motion of the middle ear ossicles in a "low-frequency" animal, the golden mole, in order to characterize the directional responses of the middle ear ossicles to airborne and seismic stimuli- and thus extend our observations to a subterranean seismic specialist, (b) systematically compare both receptor pharmacology and ionic current kinetics in the same hair cell preparation to directly test the effects of exogenous agents on tuning properties of low-frequency hair cells, (c) examine the calcium-calmodulin- dependent contractile mechanism mediating slow motility in response to extracellular stimuli in vertebrate hair cells, and (d) characterize the tuning of the peripheral auditory system of a high-frequency specialist and to determine the mechanisms subserving this tuning. The data that result will be rich in implications regarding the processing of airborne sound and substrate vibration as well as the role of efferent-mediated feedback in frequency tuning. Thus, this work is expected to provide a framework for understanding both airborne and bone-conducted sound transmission and tuning in animals, including humans. Of major current interest is the putative role of the efferent system in the genesis of frequency selectivity and protection against noise overstimulation. Ultimately, our research may lead to new therapeutic approaches to treatment of hyperacusis and noise-induced tinnitus, two known syndromes in which efferent system malfunction has been implicated.