Vestibular Reflexes

前庭反射

• 批准号: 7356148
• 负责人: WILLIAM M KING
• 金额: $ 19.31万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-05 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7356148
• 关键词: Acceleration; Address; Affect; Age; Anatomy; Animals; Behavior; Bilateral; Biological Models; Body cavities; Cavia; Chemicals; Collaborations; Darkness; Data; Detection; Elderly; Equilibrium; Exhibits; Eye; Eye Movements; Force of Gravity; Frequencies; Future; Hair Cells; Head; Health; Individual; Injection of therapeutic agent; Laboratories; Lesion; Light; Measures; Mediating; Methodology; Modeling; Modification; Motion; Natural regeneration; Operative Surgical Procedures; Organ; Oryctolagus cuniculus; Patients; Peripheral; Pharmaceutical Preparations; Physiological; Physiology; Positioning Attribute; Primates; Recovery; Recovery of Function; Reflex action; Relative (related person); Research; Research Personnel; Rotation; Semicircular canal structure; Sensory; Sensory Hair; Signal Transduction; Sledding; Space Perception; Streptomycin; Structure; Surface; System; Techniques; Temporal bone structure; Therapeutic procedure; Three-dimensional analysis; Time; Translating; Translations; Vestibular Hair Cells; Vestibular loss; Visual; body cavity; body position; eye velocity; falls; gaze; hair cell regeneration; labyrinthectomy; mortality; novel; otoconia; partial recovery; receptor; research study; response; somatosensory; vector; vestibular reflex; vestibulo-ocular reflex

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.

描述（由申请人提供）：该提案将建立一个新的研究方向，并为我的实验室开发新技术，同时促进我的实验室与我的合作社Yehoash Raphael博士之间的新合作。我们计划为未来的两组计划研究开发前庭功能的豚鼠模型：首先，对毛细胞再生的研究和生理学的研究是前庭系统功能恢复的基础，其次，对与线性加速相关的中央前庭信号进行了研究，当对临界值的检测与Gravity相关时发生，或者是在对Gravity的方向变化时发生的。 有5个特定的目标，所有目标均在警报豚鼠中进行：（1）表现并表征了对重力的头部和眼睛方向反应； （2）表征了前庭 - 胶卷（VCR）和前桥（VOR）（VOR）的频率响应； （3）表征对水平面中低频和高频线性加速器的眼反应； （4）使用AIMS 1-3中开发的方法，定量评估前庭外围双毛化学病变后动态和静态前庭反射的恢复的时间和程度； （5）确定双侧手术迷宫切除术后前庭反射的恢复时间和程度。将使用3D双搜索线圈来测量空间中的眼睛和头部位置，并使用伺服控制的转盘提供前庭刺激，该转盘会产生围绕地球垂直或水平轴的角运动或在水平面中供应的线性雪橇。病变实验完成时，将剖析和分析时间骨骼，以评估感觉毛细胞的损失和自发再生的程度。前庭反射的恢复将与毛细胞损失或随着时间的流逝可能再生有关。 该项目具有增强与健康相关的研究的重要潜力，因为目前尚无治疗程序可以替代前庭损失，尽管它对受影响的个体造成了严重后果。尽管患者可能会大大康复，但康复的程度取决于年龄和整体健康状况，以及尚未完全了解其基础的生理机制。一组拟议的研究将表征与空间取向和凝视稳定性有关的基本前庭机制，并将解决这些机制如何受到前庭末端器官的化学和外科手术修饰的影响。 该项目具有增强与健康相关的研究的重要潜力，因为目前尚无治疗程序可以替代前庭损失，尽管它对受影响的个体造成了严重后果。即使是完全补偿的患者，也可能失去平衡，并在黑暗中或暴露于不均匀的表面。跌倒行为至少与前庭损失部分有关，也是老年人死亡的重要原因。