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（由申请人提供）：毛细胞是内耳的感受器，是负责将声音和加速度转换成电信号的机械传感器，然后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，因此了解这些细胞如何正常运作以及了解它们为何如此脆弱、如何保护它们以及它们是否可以修复甚至再生非常重要。损害。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提供对耳蜗主动过程基础的理解，该过程通常使我们的听觉反应敏感并调整，而其失败会导致我们“听力困难”。先进的图像处理技术将用于确定声音产生的机械刺激如何通过耳蜗复杂的机械装置到达毛细胞。干涉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（发束）传播，以启动电响应。第二组研究涉及毛细胞将信息传递到第八脑神经（从耳朵到大脑的管道）的神经纤维的机制。在这里，生理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方法。此外，生物化学和分子生物学方法将用于鉴定参与毛细胞突触信号传导的新型蛋白质并确定其功能作用。最终的实验旨在展示耳朵在发育过程中如何组织起来，以便对每个连续频率或纯音做出反应的毛细胞沿着耳蜗的长度顺序排列。这项研究应该提供对确定单个毛细胞身份的生化基础的深入了解，并可能提出促进其再生的有效技术。