Biomechanics of the Semicircular Canals

描述（由申请人提供）：本研究旨在促进生理和病理条件下半规管生物力学的定量认识，目的是1)改善良性阵发性体位性眩晕（BPPV）的评估和治疗；2)进一步了解角运动感觉过程中的微力学和毛细胞机电因素。具体来说，这项工作旨在：量化管状结石的三维底物及其与BPPV的关系，确定毛细胞激活和传入响应动力学的微观力学对空间多样性的贡献，并确定毛细胞机电反馈在壶腹嵴中的作用。第一个目标将详细介绍在挑衅性诊断测试和管道重新定位过程中实验诱导的管道结石条件下的生物力学和神经反应。第二个目标将确定微机械和毛细胞转导电流对从半规管传递到大脑的各种神经密码的贡献。用激光干涉仪测量正弦和阶跃刺激时丘体运动的区域差异。毛细胞转导电流的空间分布将被映射到感觉上皮上，并与微力学数据进行比较，以确定每个细胞的相对贡献。研究毛细胞/毛束电运动的作用的实验将包括在内。第三个目标将研究传出前庭系统的激活以及内淋巴的电极化对毛细胞和微机械反应的影响。详细的数学模型将广泛用于解释结果和指导实验研究。将生成计算机模型和动画，显示对临床诊断测试和导管重新定位程序的反应。通过对经典和非经典BPPV的评估和治疗，研究结果有望与健康和人体状况直接相关，并对增强对半规管微观力学、毛细胞转导和机电反馈的基本认识具有长期意义。

DESCRIPTION (provided by applicant): The present work seeks to advance quantitative understanding of semicircular canal biomechanics under both physiological and pathological conditions with the goals of 1) improving the assessment and treatment of benign paroxysmal positional vertigo (BPPV) and 2) furthering the basic understanding of micromechanical and hair cell electro-mechanical factors in the process of angular motion sensation. Specifically, the work aims to: quantify the three-dimensional substrates of canalolithiasis and its relationship to BPPV, determine micromechanical contributions to spatial diversity in hair-cell activation and afferent response dynamics and, establish the role of hair-cell electro-mechanical feedback in the crista ampullaris. The first aim will detail biomechanical and neural responses under conditions of experimentally induced canalolithiasis during provocative diagnostic tests and during canalith repositioning procedures. The second aim will determine micromechanical and hair cell transduction current contributions to the diverse neural code transmitted from the semicircular canals to the brain. Regional differences in cupula motion will be measured during sinusoidal and step stimuli using a laser interferometer. The spatial distribution of haircell transduction currents will be mapped across the sensory epithelium and compared to micromechanical data to determine the relative contributions of each. Experiments to investigate the role of hair cell/bundle electro-motility will be included. The third aim will investigate the influence of activation of the efferent vestibular system and, separately, electrical polarization of the endolymph on hair-cell and micromechanical responses. Detailed mathematical models will be used extensively to interpret results and direct the experimental studies. Computer models and animations showing responses to clinical diagnostic tests and canalith repositioning procedures will be generated. Results are expected to have immediate relevance to health and the human condition through the assessment and treatment of classical and non-classical BPPV as well as long-term significance enhancing basic understanding of semicircular canal micro-mechanics, haircell transduction and electro-mechanical feedback.