Biophysics and Biomechanics of the Semicircular Canals

半规管的生物物理学和生物力学

• 批准号: 8995198
• 负责人: RICHARD D RABBITT
• 金额: $ 41.02万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-15 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8995198
• 关键词: Acoustics; Afferent Neurons; Aminoglycosides; Biomechanics; Biophysics; Brain; Brain Stem; Cochlea; Confocal Microscopy; Crista ampullaris; Data; Deposition; Development; Disease; Ear; Elderly; Electric Stimulation; Endolymph; Epithelium; Esthesia; Exhibits; Extracellular Space; Extracellular Structure; Fluorescence; Funding; Glycobiology; Glycosaminoglycans; Goals; Hair; Hair Cells; Health; Image; Investigation; Label; Labyrinth; Location; Maps; Measures; Mechanics; Motion; Movement; Natural regeneration; Neurons; Organ; Pattern; Perilymph; Physiological; Play; Population; Process; Progress Reports; Property; Recovery; Recovery of Function; Relaxation; Role; Semicircular canal structure; Sensory; Severities; Spatial Distribution; Stereocilium; Stimulus; Surface; System; Techniques; Time; Trauma; Up-Regulation; Work; afferent nerve; aminoglycoside-induced ototoxicity; electric impedance; in vivo; insight; motion sensitivity; otoconia; patch clamp; polysulfated glycosaminoglycan; repaired; response; therapeutic development; time use; voltage clamp; xylosides

DESCRIPTION (provided by applicant): The present work seeks to advance quantitative understanding of semicircular canal biophysics and biomechanics and is organized around three specific aims: 1) Examine sulfated glycosaminoglycans (GAGs) in vivo by tracking the time-course of expression in the cupula and extracellular space around stereocilia following mechanical and aminoglycoside insults. Inner ear GAGs are known to play essential roles in development, mechanics, regeneration, repair, and protection. Our experimental approach using new xyloside conjugates is revealing entirely new information about this important process. 2) Map the spatial distribution of hair bundle displacements across the sensory epithelium in response to physiological stimuli in vivo. The diverse temporal response properties of afferent neurons correlate with projections in the crista ampullaris, but we do not yet know how or if responses depend upon spatial maps of hair bundle displacements. We will measure micromechanical displacement fields while recording afferent responses innervating the same region of the crista. 3) Detail mechano-electrical transduction (MET) current adaptation and its relationship to active amplification by semicircular canal hair cells. Our recent results suggest that the most sensitive semicircular canal afferent neurons rely on hair cell amplification to increase sensitivity to low strength stimuli. We will investigate the role of MET adaptation and electrical mechanisms in this important process by tracking bundle displacements and recording from hair cells in vivo. Results are expected to have long-term impact by enhancing understanding of semicircular canal micromechanics, cupulogenesis and self-repair, amplification by hair cells, and efferent control of motion sensation by the brain.

描述（由申请人提供）：本工作旨在促进对半规管生物物理学和生物力学的定量理解，并围绕三个具体目标进行组织：1）通过跟踪机械和氨基糖苷类损伤后静纤毛周围的顶帽和细胞外空间中表达的时间过程，在体内检查硫酸化糖胺聚糖（GAG）。已知内耳GAG在发育、力学、再生、修复和保护中起重要作用。我们使用新的木糖苷共轭物的实验方法揭示了关于这一重要过程的全新信息。2)绘制体内感觉上皮对生理刺激的响应中毛束位移的空间分布图。传入神经元的不同时间响应特性与壶腹嵴中的投射相关，但我们还不知道响应如何或是否取决于发束位移的空间图。我们将测量微机械位移场，同时记录支配嵴同一区域的传入反应。3)详细的机械-电转导（MET）电流适应及其与半规管毛细胞主动放大的关系。我们最近的研究结果表明，最敏感的半规管传入神经元依赖于毛细胞扩增，以增加敏感性，低强度的刺激。我们将研究MET适应和电机制在这一重要过程中的作用，通过跟踪束位移和记录从毛细胞在体内。结果预计将有长期的影响，通过提高半规管微观力学，cupulogenesis和自我修复，毛细胞的放大，和运动感觉的传出控制大脑的理解。