Transduction Mechanism of Hair Cells

描述（由申请人提供）：毛细胞，内耳的受体，是机械传感器，负责将声音和加速度转换为电信号，然后转发给大脑进行解释。因为超过3千万的美国人患有严重的听力问题，所以了解这些细胞如何正常运作，了解它们为什么如此脆弱，如何保护它们，以及它们是否可以修复，甚至在受损后再生，都是很重要的。本研究旨在探讨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，这个过程通常会使我们的听觉反应变得敏感和调节，如果失败了，我们就会“听力不好”。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复杂的机械装置并到达毛细胞。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受体细胞器（毛发束）传播，从而引发电反应。第二组研究涉及毛细胞将信息传递给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导管。在这里，生理学技术将提供一种确定毛细胞和神经末梢之间突触信号传导机制的手段。此外，生物化学和分子生物学的方法将用于鉴定新的蛋白质参与突触信号的毛细胞和建立其功能作用。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，这样毛细胞就会对每个连续的频率或纯音做出反应，并沿着耳蜗的长度顺序排列。这项研究将为确定单个毛细胞的身份提供深入的生化基础，并可能提出促进其再生的有效技术。

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.