Vestibulo-Collic Reflex: A Quantitative Assay of Vestibular Function in Aging Mic

描述（由申请人提供）：在小鼠中，缺乏用于前庭功能的容易施用和选择性测试是前庭系统研究的显著障碍，特别是对于那些寻求定量评估与衰老或药物治疗或遗传操作的功效相关的功能损失的研究。本提案的总体目标是开发和验证易于使用的小鼠功能性前庭试验，以用于此类研究。有两个具体目标。第一个目的是优化测量前庭-结肠反射（VCR）的动物进行整体动态旋转地球垂直和地球水平轴。初步的数据表明这种方法的可行性，但前庭系统的反应的贡献程度仍然必须确定。由于小鼠的头部方向与重力有关，我们还将开发一种基于静态倾斜期间头部位置的视频记录分析的测量头部方向的简化方法。这些测试是基于这样的假设，即颈部反射依赖于前庭感觉流入，并在整个身体在空间运动期间起到稳定头部位置和方向的作用。感觉细胞的损失或周围神经支配的变化应导致前庭颈反射的可测量的变化。目的2将通过比较VCR的变化与外周形态学或突触组织的变化，评估老龄小鼠队列中静态和动态VCR的变化。将测试12、18、24和30个月龄的C57 BL/6小鼠以确定前庭颈反射的功效是否随年龄而下降。将前庭测试数据与评估前庭和运动功能的非特异性方法（如“平衡木和旋转杆测试”）进行比较。将对老年小鼠的颞骨进行形态学分析，以确定感觉毛细胞或具有萼末端的毛细胞（I型毛细胞）的数量是否存在年龄相关变化。

DESCRIPTION (provided by applicant): In mice the lack of an easily administered and selective test for vestibular function is a significant impediment for studies of the vestibular system, especially for those studies that seek to assess quantitatively functional losses associated with aging or the efficacy of drug treatments or genetic manipulations. The overall goal of this proposal is to develop and validate easily used functional vestibular tests for mice to use in such studies. There are 2 specific aims. The first aim is to optimize measurements of the vestibulo-collic reflex (VCR) in animals subjected to en bloc dynamic rotation about earth vertical and earth horizontal axes. Preliminary data suggests the feasibility of this approach, but the extent of the vestibular system's contribution to the response must still be determined. Since mice orient their heads with respect to gravity, we will also develop a, simplified method of measuring head orientation based on an analysis of video recordings of head position during static tilts. These tests are based on the hypothesis that the neck reflexes are dependent on vestibular sensory inflow and act to stabilize head position and orientation during whole body motion in space. Sensory cell losses or peripheral innervation changes should result in measurable changes in vestibular neck reflexes. Aim 2 will assess changes in the static and dynamic VCR in a cohort of aging mice by comparing changes in VCR with changes in peripheral morphology or synaptic organization. C57BL/6 mice aged 12,18, 24 and 30 months will be tested to determine if the efficacy of vestibular neck reflexes declines with age. The vestibular test data will be compared to non-specific methods of assessing vestibular and motor function such as "balance beam and rota-rod tests. The temporal bones of the aged mice will be subjected to morphological analyses to determine if there are age related changes in the numbers of sensory hair cells or hair cells with calyx endings (Type I hair cells).