Transduction Mechanism of Hair Cells

描述（由申请人提供）：毛细胞是内耳的受体，是负责将声音和加速度转换为电信号的机械传感器，然后可以将电信号转发到大脑进行解释。由于超过3000万美国人患有严重的听力问题，我们了解这些细胞如何正常工作，以及我们了解为什么它们如此脆弱，如何保护它们，以及它们是否可以在损伤后修复甚至再生都很重要。本研究旨在探索毛细胞功能的三个重要方面。最初的一系列实验应该能让我们了解耳蜗活动过程的基础，耳蜗活动过程通常会使我们的听觉反应敏感和协调，而耳蜗活动过程的失败会让我们“重听”。“先进的图像处理技术将用于确定来自声音的机械刺激如何通过耳蜗的复杂机械装置到达毛细胞。干涉测量实验将揭示这些信号如何通过每个毛细胞的机械感受器细胞器（毛束）传播，以启动电反应。第二组研究涉及毛细胞将信息传递到第八脑神经的神经纤维的机制，第八脑神经是从耳朵到大脑的管道。在这里，生理学技术将提供一种手段，以确定毛细胞和神经末梢之间的突触信号的机制。此外，生物化学和分子生物学的方法将被用来确定新的蛋白质参与突触信号的毛细胞，并建立其功能的作用。最后的实验旨在证明耳朵在发育过程中是如何组织起来的，因此对每个连续频率或纯音有反应的毛细胞是沿着耳蜗的长度顺序排列的。这项调查应提供深入了解的生化基础，具体说明个别毛细胞的身份，并可能建议有效的技术，促进其再生。

DESCRIPTION (provided by applicant): Hair cells, the receptors of the internal ear, are the mechanical sensors responsible for converting sounds and accelerations into electrical signals that can then be forwarded to the brain for interpretation. Because over 30 million Americans suffer from significant hearing problems, it is important both that we understand how these cells function normally and that we to learn why they are so vulnerable, how they may be protected, and whether they can be repaired or even regenerated after damage. The present studies are meant to explore three important aspects of hair-cell function. The initial set of experiments should provide an understanding of the basis of the cochlear active process that normally sensitizes and tunes our auditory responsiveness, and whose failure leaves us "hard of hearing." Advanced image-processing techniques will be used to determine how mechanical stimuli stemming from sounds make their way through the complex mechanical apparatus of the cochlea and to the hair cells. Interferometric experiments will disclose how these signals propagate through each hair cell's mechanical- receptor organelle, the hair bundle, to initiate an electrical response. A second group of investigations involves the mechanism by which hair cells transmit information to the nerve fibers of the eighth cranial nerve, the conduit from the ear to the brain. Here physiological techniques will provide a means of ascertaining the mechanism of synaptic signaling between hair cells and nerve terminals. In addition, biochemical and molecular-biological approaches will be used to identify novel proteins involved in synaptic signaling by hair cells and to establish their functional roles. The final experiments are intended to demonstrate how the ear becomes organized during development so that the hair cells responsive to each successive frequency, or pure tone, are sequentially arranged along the length of the cochlea. This investigation should provide insight into the biochemical basis for specifying the identity of individual hair cells and may suggest effective techniques for fostering their regeneration.