Biophysics and Biomechanics of the Semicircular Canals

半规管的生物物理学和生物力学

• 批准号: 8889328
• 负责人: RICHARD D RABBITT
• 金额: $ 3.6万
• 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/8889328
• 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; Relative (related person); 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）：目前的工作旨在提高对半圆形管生物物理学和生物力学的定量理解，并围绕三个具体目的进行组织：1）通过跟踪cubula和细胞外空间的表达时间顺序，然后在体生中检查硫酸化的糖胺聚糖（GAGS）在体内，然后遵循cub虫的表达时间。众所周知，内耳堵塞在发展，力学，再生，修复和保护中起着重要作用。我们使用新型木糖苷缀合物的实验方法正在揭示有关此重要过程的全新信息。 2）响应体内生理刺激，绘制头发束位移的空间分布。传入神经元的各种时间响应特性与crista ampullaris的投影相关，但我们尚不知道响应如何或是否取决于束束位移的空间图。我们将在记录CRISTA同一区域的传入响应时测量微机械位移场。 3）详细的机械电气转导（MET）电流适应及其与半圆形管细胞活跃扩增的关系。我们最近的结果表明，最敏感的半圆形管传入神经元依赖毛细胞扩增来增加对低强度刺激的敏感性。我们将通过跟踪束位移并记录体内毛细胞的记录，研究MET适应和电机制在这一重要过程中的作用。预计结果将通过增强对半圆形管微力学，杯状和自我修复，毛细胞扩增以及对大脑运动感觉的传递控制，从而产生长期影响。