An innovative instrument cluster for the integrative behavioral analysis of mouse mutants with perturbed neuronal connectivity

项目概要/摘要： 此SIFAR资助申请旨在获得一个集成仪表组， 允许对一系列小鼠进行灵敏、可靠和无偏见的神经行为表型分析 来自五个主要用户的突变体模拟神经退行性疾病。这些条件 由神经胶质细胞中的基因突变引起，导致髓鞘形成和轴突异常 退化Noldus信息技术公司的协同仪表组 包括Noldus CatWalk XT、Noldus Erasmus Ladder和Noldus EthoVision XT开放视野分析系统，具有自定义配置，可同时观察up 八只动物CatWalk XT是一种高度敏感的基于视频的自动步态分析 利用爪印强度量化步态模式沿着的时空特征的工具 和小鼠的步行速度。ErasmusLadder是一个自动化系统， 评估小鼠的平衡、协调和运动能力。动物运动轨迹跟踪系统 开放式视频跟踪系统可以自动监测和统计分析 活动，许多走动参数和刻板行为在自由活动的小鼠， 批量采集模式。这五名研究人员目前使用传统的神经行为学方法， 方法（例如，基于墨水足迹、旋转杆、爬杆分析）， 易受人为因素影响，易于发生高度变化，具有固有的主观性， 动物配套的组合仪表将尽量减少这些缺点， 通过数据采集的自动化和计算机化并行增加吞吐量。 该设备还将与另一个仪表组协同工作， 调查人员对感觉障碍进行具体分析。所有工具一起将 使研究者能够全面研究他们的感觉运动改变， 神经退行性小鼠疾病模型。这将有助于确定更多的 可靠的神经行为生物标志物，这将有助于测量疾病 治疗组的进展和比较。支持这一点的基本赠款项目 该提案将大大受益于三方组合仪表的额外能力 以及增强的严谨性、再现性和透明度。

Project Summary/Abstract: This S10 SIFAR grant application seeks funds to acquire an integrated instrument cluster to allow the sensitive, reliable, and unbiased neurobehavioral phenotyping of a range of mouse mutants from five major users modeling neurodegenerative conditions. These conditions arise from gene mutations in glial cells resulting in aberrant myelination and axon degeneration. The synergistic instrument cluster from Noldus Information Technology comprises the Noldus CatWalk XT, the Noldus ErasmusLadder, and the Noldus EthoVision XT open-field analysis system with custom configuration for simultaneous observation of up to eight animals. The CatWalk XT is a highly sensitive video-based automated gait analysis tool quantifying spatiotemporal characteristics of gait patterns along with paw print intensities and ambulatory velocities of mice. The ErasmusLadder is an automated system for the assessment of balance, coordination and locomotor capacity in mice. The EthoVision XT open-field video-tracking system allows automated monitoring and statistical analysis of activity, numerous ambulatory parameters, and stereotypic behavior in freely moving mice in batch-acquisition mode. The five investigators currently use conventional neurobehavioral methods (e.g., ink-based footprint, rotarod, pole-climb analysis) that are particularly laborious, susceptible to artefacts, prone to high variability, inherently subjective, and distressing to animals. The complementary instrument cluster will minimize these shortcomings, while in parallel increasing throughput via the automation and computerization of data acquisition. The equipment will also synergize with another instrument cluster accessible to the investigators for the specific analysis of sensory impairment. All instruments together will allow the investigators to comprehensively study sensorimotor alterations in their neurodegenerative mouse disease models. This will allow for the identification of more reliable neurobehavioral biomarkers, which will facilitate the measurement of disease progression and comparision of treatment groups. The base grant projects that support this proposal will greatly benefit from the additional capabilities of the tripartite instrument cluster as well as from enhanced rigor, reproducibility, and transparency.