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

前庭结肠反射：老化麦克风前庭功能的定量测定

• 批准号: 7535508
• 负责人: WILLIAM M KING
• 金额: $ 18.86万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7535508
• 关键词: Age; Aging; Aging-Related Process; Animal Model; Animals; Behavior; Behavioral; Biological Assay; C57BL/6 Mouse; Cells; Data; Disease; Elderly; Equilibrium; Esthesia; Evaluation; Force of Gravity; Goals; Hair Cells; Head; Individual; Intervention; Longevity; Measurable; Measurement; Measures; Methods; Morphology; Motion; Motor; Mus; Neck; Pathology; Performance; Peripheral; Pharmaceutical Preparations; Positioning Attribute; Posture; Principal Investigator; Protective Agents; Reflex action; Relative (related person); Research; Rodent; Rotation; Self Perception; Sensory; Sensory Hair; Synapses; System; Temporal bone structure; Testing; Type I Hair Cell; Vestibular Function Tests; Vestibular loss; Vestibular nucleus structure; Video Recording; age related; aged; base; cohort; drug efficacy; falls; functional loss; genetic manipulation; nerve supply; novel; otoconia; ototoxicity; programs; protective efficacy; response; retinal rods; vestibular reflex

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).

描述（由申请人提供）：在小鼠中，缺乏对前庭功能的易于施用和选择性测试是对前庭系统研究的重要障碍，特别是对于那些试图评估与衰老或药物治疗或遗传操作相关的定量功能损失的研究。该提案的总体目标是开发和验证易于在此类研究中使用的小鼠使用的功能前庭测试。有2个具体目标。第一个目的是优化在围绕地球垂直和地球水平轴的动态旋转的动物中的前庭 - 胶体反射（VCR）的测量。初步数据表明这种方法的可行性，但是仍必须确定前庭系统对响应的贡献的程度。由于小鼠在重力方面的头部定向，我们还将根据对静态倾斜期间头部位置的视频记录分析来开发一种简化的测量头方向的方法。这些测试基于以下假设：颈部反射取决于前庭感觉流入和作用以稳定空间中全身运动期间的头部位置和方向。感觉细胞损失或周围神经支配的变化应导致前庭颈部反射的可测量变化。 AIM 2将通过比较VCR的变化与外围形态或突触组织的变化来评估衰老小鼠队列中静态和动态VCR的变化。将测试年龄12,18、24和30个月的C57BL/6小鼠，以确定前庭颈部反射的功效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异性方法进行比较，例如“平衡束和旋转rod测试。老年小鼠的时间骨骼将经过形态学分析，以确定与Calyx Endings（I型毛细胞）的感官毛细胞或毛细胞的年龄相关的变化。