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

描述(由申请人提供)：在小鼠中，前庭功能缺乏易于管理和选择性的测试是前庭系统研究的一个重大障碍，特别是对于那些试图定量评估与衰老或药物治疗或基因操作的疗效相关的功能损失的研究。这项建议的总体目标是开发和验证易于使用的前庭功能测试，供小鼠在此类研究中使用。有两个具体目标。第一个目标是优化动物在整体绕地球垂直和水平轴动态旋转时前庭结肠反射(VCR)的测量。初步数据表明这种方法是可行的，但前庭系统对反应的贡献程度仍需确定。由于小鼠根据重力来定位头部，我们还将开发一种基于对静态倾斜过程中头部位置的视频记录的分析来测量头部方位的简化方法。这些测试基于这样的假设，即颈部反射依赖于前庭感觉的流入，并在整个身体在空间中运动的过程中起到稳定头部位置和方向的作用。感觉细胞丢失或周围神经变化应导致前庭颈部反射的可测量变化。目的2将通过比较VCR的变化与外周形态或突触组织的变化来评估一组老年小鼠静态和动态VCR的变化。将对12、18、24和30个月龄的C57BL/6小鼠进行测试，以确定前庭颈部反射的有效性是否随着年龄的增长而下降。前庭测试数据将与评估前庭和运动功能的非特定方法进行比较，如平衡木和旋转杆测试。老年小鼠的颞骨将接受形态分析，以确定感觉毛细胞或带有花萼末端的毛细胞(I型毛细胞)的数量是否与年龄有关。

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).