Biophysics and Biomechanics of the Semicircular Canals

描述(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了解，并围绕三个具体目标进行组织：1)通过跟踪机械性和氨基糖苷类损伤后立体纤毛周围杯状和细胞外间隙中表达的时间进程，在体内检测硫酸糖胺多聚糖(GAG)。众所周知，内耳插管在发育、机械、再生、修复和保护方面发挥着重要作用。我们使用新的木糖苷共轭化合物的实验方法揭示了关于这一重要过程的全新信息。2)绘制感觉上皮毛束位移在生理刺激下的空间分布图。传入神经元的不同时间反应特性与壶腹脊的投射相关，但我们还不知道反应如何或是否依赖于毛束位移的空间地图。我们将测量微机械位移场，同时记录支配同样区域的传入反应。3)MET电流适应及其与半规管毛细胞主动扩增的关系。我们最近的结果表明，最敏感的半规管传入神经元依赖于毛细胞的放大来增加对低强度刺激的敏感性。我们将通过跟踪体内毛细胞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。这些结果有望通过加强对半规管微观力学、杯突发生和自我修复、毛细胞的放大以及大脑对运动感觉的传出控制的理解而产生长期影响。

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.