Biophysics and Biomechanics of the Semicircular Canals

描述（由申请人提供）：目前的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)通过跟踪力学和氨基糖苷损伤后锥体和立纤毛周围细胞外空间表达的时间过程来检测体内硫酸氨基糖胺聚糖（GAGs）。众所周知，内耳gag在发育、力学、再生、修复和保护中起着重要作用。我们使用新的木糖缀合物的实验方法揭示了关于这一重要过程的全新信息。2)绘制毛束位移在生理刺激下的空间分布。传入神经元的不同时间反应特性与壶腹嵴的投射相关，但我们还不知道反应如何或是否依赖于毛束位移的空间图。我们将测量微机械位移场，同时记录神经支配christa同一区域的传入反应。3)详细的机电转导（MET）电流适应及其与半规管毛细胞主动扩增的关系。我们最近的研究结果表明，最敏感的半圆管传入神经元依靠毛细胞扩增来增加对低强度刺激的敏感性。我们将通过跟踪毛细胞在体内的束位移和记录来研究MET适应和电机制在这一重要过程中的作用。该研究结果有望通过加强对半圆管微观力学、毛细胞发生和自我修复、毛细胞扩增以及大脑对运动感觉的传出控制的理解产生长期影响。

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.