Vestibular Reflexes

描述(由申请人提供)：这项建议将为我的实验室建立一个新的研究方向并开发新的技术，同时促进我的实验室和我的合作者Yehoash Raphael博士之间的新合作。我们计划在未来为两组计划中的研究开发豚鼠前庭功能模型：第一，毛细胞再生和前庭系统功能恢复的生理学研究；第二，与检测到线加速相关的前庭中央信号的研究，这发生在头部相对于重力的方向改变或头部在空间惯性平移时。 在清醒的豚鼠身上有5个特定的目标：(1)展示和表征头部和眼睛对重力的定向反应；(2)表征前庭-大脑皮层(VCR)和前庭-眼(VOR)反射围绕多个轴的频率反应；(3)表征眼睛对水平面中低频和高频线性加速的反应；(4)使用AIMS 1-3中发展的方法学，定量评估双侧前庭周围化学损伤后动态和静态前庭反射恢复的时间过程和程度；以及(5)确定双侧手术迷路切除后前庭反射恢复的时间和程度(如果有)。将使用3D双搜索线圈测量眼睛和头部在空间中的位置，并使用伺服控制的转台产生围绕地球垂直或水平轴的角运动或在水平面上加速的线性雪橇来提供前庭刺激。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丧失和自发再生的程度。前庭反射的恢复将与毛细胞丢失的程度或随着时间的推移可能再生相关。 这个项目在加强与健康相关的研究方面有很大的潜力，因为目前还没有治疗程序来取代前庭缺失，尽管它对受影响的个人造成了严重的后果。虽然患者可能会基本恢复，但恢复的程度取决于年龄和整体健康状况，其背后的生理机制尚不完全清楚。这组拟议的研究将描述与空间定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组织的化学和手术修改的影响的问题。项目叙述： 这个项目在加强与健康相关的研究方面有很大的潜力，因为目前还没有治疗程序来取代前庭缺失，尽管它对受影响的个人造成了严重的后果。即使是完全补偿的患者也可能会失去平衡，在黑暗中摔倒，或者暴露在不平坦的表面上。跌倒行为，至少部分与前庭丧失有关，也是老年人死亡的一个重要原因。

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.