Transduction Mechanism of Hair Cells

毛细胞的转导机制

• 批准号: 7844120
• 负责人: ALBERT JAMES HUDSPETH
• 金额: $ 0.5万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2009-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7844120
• 关键词: Acceleration; Acoustic Nerve; Acoustic Stimulation; Algorithms; American; Amphibia; Auditory; Basilar Papilla; Biochemical; Biological; Brain; Cell physiology; Characteristics; Chickens; Cochlea; Complex; Development; Ear; Epithelium; Exocytosis; Failure; Fostering; Frequencies; Hair; Hair Cells; Hearing; Hearing problem; Human; Immunofluorescence Immunologic; In Situ Hybridization; In Vitro; Individual; Intervention; Investigation; Labyrinth; Learning; Left; Length; Maps; Measurement; Measures; Mechanics; Membrane; Membrane Potentials; Molecular; Molecular Analysis; Movement; Natural regeneration; Nature; Nerve; Nerve Fibers; OTOF gene; Optics; Organ; Organ of Corti; Organelles; Physiological; Preparation; Process; Property; Proteins; Rana; Research Personnel; Retina; Role; Screening procedure; Sensory; Series; Signal Transduction; Site-Directed Mutagenesis; Specific qualifier value; Stereocilium; Stimulus; Surface; Synapses; Synaptic Transmission; Techniques; Testing; Video Microscopy; Yeasts; Zebrafish; afferent nerve; base; cDNA Library; cell motility; deafness; image processing; insight; mathematical model; novel; postsynaptic; pressure; presynaptic; programs; receptor; repaired; research study; response; ribbon synapse; sensor; sound; stem; tongue papilla; yeast two hybrid system

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.

描述(申请人提供)：毛细胞是内耳的接收器，是负责将声音和加速度转换为电信号的机械传感器，然后可以转发到大脑进行解释。由于3000多万美国人患有严重的听力问题，重要的是我们要了解这些细胞是如何正常运作的，我们还必须了解它们为什么如此脆弱，如何保护它们，以及它们在受损后是否可以修复甚至再生。目前的研究旨在探索毛细胞功能的三个重要方面。最初的一组实验应该能让我们了解耳蜗活动过程的基础，这一过程通常会敏化和调节我们的听觉反应，而它的失败会让我们“听力不佳”。先进的图像处理技术将被用来确定声音产生的机械刺激是如何通过复杂的机械耳蜗器到达毛细胞的。干涉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--发束--传播，以启动电反应。第二组研究涉及毛细胞向第八脑神经的神经纤维传递信息的机制，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机制。此外，还将使用生化和分子生物学方法来识别毛细胞参与突触信号传递的新蛋白质，并确定它们的功能作用。最后的实验旨在展示耳朵在发育过程中是如何组织起来的，以便对每个连续频率或纯音做出反应的毛细胞沿着耳蜗长的顺序排列。这项研究应该为确定单个毛细胞的身份提供深入的生化基础，并可能为促进它们的再生提供有效的技术。