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）：该提案将为我的实验室建立一个新的研究方向并开发新技术，同时促进我的实验室和我的共同研究员 Yehoash Raphael 博士的实验室之间的新合作。我们计划为未来的两组计划研究开发前庭功能豚鼠模型：第一，对毛细胞再生和前庭系统功能恢复的生理学的研究；第二，对中枢前庭的研究与线性加速度检测相关的信号，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。 有 5 个具体目标，全部在警觉的豚鼠身上进行：（1）展示并表征头部和眼睛对重力的定向反应； (2) 表征前庭结肠 (VCR) 和前庭眼 (VOR) 反射绕多个轴的频率响应； (3) 表征眼睛对水平面低频和高频线性加速度的反应； (4) 使用目标 1-3 中开发的方法，定量评估双侧前庭周边化学损伤后动态和静态前庭反射恢复的时间过程和程度； (5) 确定双侧迷路手术切除后前庭反射恢复的时间过程和程度（如果有）。眼睛和头部在太空中的位置将使用 3D 双搜索线圈进行测量，前庭刺激将使用伺服控制转盘提供，该转盘产生绕地球垂直或水平轴的角运动或在水平面加速的线性雪橇。损伤实验完成后，将对颞骨进行解剖和分析，以评估感觉毛细胞的损失和自发再生的程度。前庭反射的恢复与毛细胞损失的程度或随着时间的推移可能的再生程度相关。 该项目具有加强健康相关研究的巨大潜力，因为尽管前庭丧失对受影响的个体造成严重后果，但目前尚无可用的治疗方法来替代前庭丧失。尽管患者可能会大幅康复，但恢复程度取决于年龄和整体健康状况，并且其背后的生理机制尚不完全清楚。这组拟议的研究将描述涉及空间定向和凝视稳定性的基本前庭机制，并将解决这些机制如何受到前庭末端器官的化学和手术修饰影响的问题。项目叙述： 该项目具有加强健康相关研究的巨大潜力，因为尽管前庭丧失对受影响的个体造成严重后果，但目前尚无可用的治疗方法来替代前庭丧失。即使完全代偿的患者也可能会失去平衡并跌倒在黑暗中或暴露在不平坦的表面上。跌倒行为（至少部分与前庭功能丧失有关）也是老年人死亡的一个重要原因。