Vestibular Reflexes

描述（由申请人提供）：本提案将为我的实验室建立一个新的研究方向和开发新的技术，同时促进我的实验室与我的共同研究者Yehoash Raphael博士之间的新的合作。我们计划开发一个前庭功能的豚鼠模型，用于未来的两组计划研究：第一，研究毛细胞再生和前庭系统功能恢复的生理学基础；第二，研究与检测线性加速度相关的前庭中枢信号，当头部相对于重力的方向改变或头部在空间中惯性平移时，会发生线性加速度。

DESCRIPTION (provided by applicant): This proposal will establish a new research direction and develop novel techniques for my laboratory while promoting a new collaboration between my lab and that of my co- investigator, Dr. Yehoash Raphael. We plan to develop a guinea pig model of vestibular function for two sets of planned studies in the future: first, a study of hair cell regeneration and the physiology that underlies recovery of function in the vestibular system, and second, a study of central vestibular signals related to detection of linear acceleration, which occurs when head orientation with respect to gravity is changed or when the head is translated inertially in space. There are 5 specific aims, all performed in alert guinea pigs: (1) demonstrate and characterize head and eye orientation responses to gravity; (2) characterize the frequency responses of the vestibulo-collic (VCR) and vestibulo-ocular (VOR) reflexes about multiple axes; (3) characterize ocular responses to low and high frequency linear accceleration in the horizontal plane; (4) using methodology developed in Aims 1-3, quantitatively assess the time course and extent of recovery of dynamic and static vestibular reflexes after bilateeral chemical lesions of the vestibular periphery; and (5) determine the time course and extent of recovery, if any, of vestibular reflexes after bilateral surgical labyrinthectomies. Eye and head position in space will be measured using 3D dual search coils and vestibular stimulation will be provided using a servo- controlled turntable that generates angular motion about earth vertical or horizontal axes or a linear sled that accelerates in the horizontal plane. At the completion of lesion experiments, temporal bones will be dissected and analyzed to assess the extent of loss and spontaneous regeneration of sensory hair cells. Recovery of vestibular reflexes will be correlated with the extent of hair cell loss or possible regeneration over time. This project has significant potential to enhance health related research since no therapeutic procedure is currently available to replace vestibular loss despite its serious consequences for affected individuals. Although patients may recover substantially, the extent of recovery depends on age and overall health, and the physiological mechanisms that underlie it are not fully understood. The set of proposed studies will characterize the fundamental vestibular mechanisms involved in spatial orientation and gaze stability and will address the question of how these mechanisms are affected by both chemical and surgical modification of the vestibular end organs.Project Narrative: This project has significant potential to enhance health related research since no therapeutic procedure is currently available to replace vestibular loss despite its serious consequences for affected individuals. Even fully compensated patients may lose their balance and fall in darkness or if exposed to uneven surfaces. Falling behavior, at least partially related to vestibular loss, is also a significant cause of mortality in the elderly.