Biomechanics of the Semicircular Canals

描述（申请人提供）：本研究旨在提高对生理和病理条件下半规管生物力学的定量理解，目标是：1）改善良性阵发性位置性眩晕（BPPV）的评估和治疗，2）量化角运动感觉的微机械基底，以及3）提供对活性毛发的作用的新理解，半规管感觉传导中的束运动。首先，结果将详细说明在实验诱导的肾管结石（肾管结石）条件下对大脑的病理生物力学和神经输入。实验将集中在放大，可能会发生的颗粒从壶腹移动到运河管道和衰减，可能会发生的小颗粒从管道的中心移动到运河壁。第二，实验结果将确定微机械的贡献下的神经表示的角度头部运动和不同的神经代码从半规管传输到大脑。第三，这些数据将确定活跃的毛细胞/毛束能动性在角运动感觉的敏感性和选择性中的作用。还将确定传出前庭系统的作用和内淋巴的电极化对毛细胞和微机械响应的作用。通过经典和非经典BPPV的评估和治疗，预期结果与健康和人类状况直接相关，以及长期意义，增强对半规管微观力学，毛细胞活动过程的基本理解，转导和大脑对运动感觉的传出控制。公共卫生相关性：前庭系统的疾病是使人衰弱的且常见的，折磨大约30%的65岁以上的人口，仅在美国每年就有超过500万患者就诊于医生[22，23]。本申请直接涉及与良性阵发性位置性眩晕相关的生物力学基质和病理传入神经反应以及影响杯状力学、毛束力学和毛细胞机械-电转导（MET）的病症。结果预计将导致一个更完整的定量描述如何canalithiases改变传入输入到大脑，并改善诊断程序和治疗方法canalithiases。从长远来看，关于适应的微机械基质和毛束运动的作用的知识将有助于我们从根本上理解神经代码如何在健康中产生以及如何在疾病中改变。

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), 2) quantifying the micromechanical substrates of angular motion sensation and 3) providing a new understanding of the role of active hair- bundle motility in sensory transduction by the semicircular canals. First, results will detail pathological biomechanical and neural inputs to the brain under conditions of experimentally induced canalithiasis (canalolithiasis). Experiments will focus on amplification that may occur as particles move from the ampulla to the canal duct and the attenuation that may occur as small particles move from the center of the duct to the canal wall. Second, experimental results will determine micromechanical contributions underlying the neural representation of angular head movements and the diverse neural code transmitted from the semicircular canals to the brain. Third, the data will determine the role of active hair cell/bundle motility in the sensitivity and selectivity of angular motion sensation. The action of the efferent vestibular system and, separately, electrical polarization of the endolymph on hair-cell and micromechanical responses will also be determined. 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 micromechanics, hair-cell active processes in transduction and efferent control of motion sensation by the brain. PUBLIC HEALTH RELEVANCE: Disorders of the vestibular system are debilitating and common, afflicting approximately 30% of the population over the age of 65 and accounting for over 5 million patient visits to the physician each year in the U.S. alone [22, 23]. The present application is directly relevant to the biomechanical substrates and pathological afferent neural responses associated with benign paroxysmal positional vertigo and conditions affecting cupular mechanics, hair-bundle mechanics and hair-cell mechano- electrical transduction (MET). Results are expected to lead to a more complete quantitative description of how canalithiasis alters afferent inputs to the brain, and to improved diagnostic procedures and therapeutic approaches for canalithiasis. In the longer term, knowledge to be gained regarding micromechanical substrates of adaptation and the role of hair bundle motility will contribute to our fundamental understanding of how the neural code is generated in health and how it is altered in disease.