Biomechanics of the Semicircular Canals

描述（由申请人提供）：本研究旨在促进对生理和病理条件下半规管生物力学的定量理解，以达到以下目标：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力学基础；3)对活跃的毛束运动在半规管感觉转导中的作用提供新的认识。首先，结果将详细说明在实验诱导的管状石症（管状石症）条件下对大脑的病理生物力学和神经输入。实验将集中在粒子从壶腹移动到管腔导管时可能发生的放大和小粒子从管腔中心移动到管壁时可能发生的衰减。其次，实验结果将确定微力学的贡献背后的神经表征角头部运动和不同的神经代码从半规管传递到大脑。第三，数据将确定活跃的毛细胞/束运动在角运动感觉的敏感性和选择性中的作用。传出前庭系统的作用，以及内淋巴的电极化对毛细胞和微机械反应的作用也将被确定。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类状况直接相关，并具有长期意义，增强对半规管微力学、毛细胞活动过程在大脑运动感觉的转导和传出控制中的基本理解。公共卫生相关性：前庭系统疾病使人衰弱且很常见，大约30%的65岁以上的人患有前庭系统疾病，仅在美国每年就有超过500万的患者就诊[22,23]。目前的应用与良性阵发性位置性眩晕的生物力学基础和病理传入神经反应以及影响毛囊力学、毛束力学和毛细胞力学-电转导（MET）的条件直接相关。研究结果有望导致对导管病如何改变大脑传入输入的更完整的定量描述，并改进导管病的诊断程序和治疗方法。从长远来看，关于适应的微机械底物和毛束运动的作用的知识将有助于我们对神经密码如何在健康中产生以及如何在疾病中改变的基本理解。

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.