Automated Touchscreen-Piezo Monitoring of Mouse Cognition, Activity and Sleep

描述(申请人提供)：数百万人患有慢性神经变性，导致阿尔茨海默病和其他痴呆症。数以百万计的人因睡眠不足、压力、昼夜节律紊乱和精神障碍而遭受急性认知障碍。许多药物副作用损害认知，例如安定导致健忘症。为了开发更好的治疗方法，减少药物副作用，研究人员需要新的测试方法和仪器。目前，啮齿动物最常用的三种行为认知任务，即Morris水迷宫、放射臂和Barnes迷宫，主要评估空间记忆。由于不同的行为分析总是需要不同的专门技术和仪器，研究人员很少同时对认知和睡眠等影响认知的基本神经行为进行评估。使用触摸屏的视觉辨别方法经常在临床上使用，最近在Rothblat博士的实验室(co-PI)已被用于小鼠认知评估。然而，目前还没有用于认知分析的标准化和自动化触摸屏设备。在这里，我们建议将触摸屏方法与集成的传感器技术相结合，以创建一种仪表化的家庭，称为SmartCageTM。使用SmartCage的研究人员可以进行行为认知测试，并同时监测老鼠在家中的睡眠和醒来活动。我们的具体目标是：1.设计和设计一系列基于集成电路和微控制器的无线模块化设备(模块)，用于在小鼠家中进行认知和基本神经行为评估。这些模块包括用于认知任务的触摸屏，用于位置和运动检测的红外(IR)矩阵，以及用于睡眠/唤醒监测的压电式传感器。2.开发统一的图形用户界面和直观的程序，以实现触摸屏程序、数据采集和认知与其他神经行为的综合分析的自动化。3.评估SmartCage的能力和局限性，方法是对原型进行可行性测试，并使用突变小鼠模型(rl-/)和NMDA拮抗剂MK801对原始触摸屏设备进行基准测试，以了解其对认知和运动的影响。这款多功能且宜居的SmartCage将提供视觉辨别认知测试，并使认知与其他行为方面(如睡眠和清醒活动)的集成测试成为可能，从而揭示认知和其他神经行为的相互依赖。我们的新方法是灵活的，可扩展的，并为第二阶段研究中开发的高通量认知测试系统提供了基础。7.NARRITIVE项目数百万人患有阿尔茨海默病和其他痴呆症，但没有预防药物和有效的治疗方法。为了开发更好的疗法，我们需要更好的测试技术。在这里，我们建议开发一种自动触摸屏-压电工具包，用于有效地测试药物对动物学习和记忆的影响，这将补充和增强现有的认知测试。

DESCRIPTION (provided by applicant): Millions of people suffer chronic neurodegeneration, leading to Alzheimer's disease and other dementias. Millions more suffer acute cognitive impairment from sleep deprivation, stress, circadian disturbances, and psychiatric disorders. Many medication side effects impair cognition, for example diazepam causing amnesia. To develop better therapies and decrease medication side effects, researchers need new testing methods and instruments. Currently, three of the most commonly used behavioral cognitive tasks, the Morris water maze, the radial-arm and the Barnes mazes in rodents primarily assess spatial memory. Since different behavioral assays always require different specialized techniques and apparatuses, researchers rarely conduct simultaneous assessments of cognition and basic neurobehaviors such as sleep, known to influence cognition. Visual discrimination using a touchscreen method, frequently used in clinics, has been adapted recently for mouse cognition assessment in Dr. Rothblat's laboratory (the co-PI). However, no standardized and automated touchscreen apparatuses for cognitive assays are commercially available. Here we propose to incorporate the touchscreen method with integrated sensor technologies to create an instrumented homecage, termed the SmartCageTM. Researchers using the SmartCage can conduct behavioral cognitive testing, and simultaneously monitor sleep and wake activity in mice at their homecages. Our Specific Aims are to: 1. Design and engineer a series of integrated circuit and microcontroller based wireless modular devices (modules) for cognitive and basic neurobehavioral assessments in a mouse homecage. These modules include the touchscreen for cognitive tasks, infrared (IR) matrices for positional and locomotor detections, and piezoelectric sensors for sleep/wake monitoring. 2. Develop a uniform graphic user interface and intuitive programs to enable automation of the touchscreen procedure, data acquisition, and integrative analysis of cognition with other neurobehaviors. 3. Evaluate the capabilities and limitations of the SmartCage by performing feasibility tests on the prototype, and benchmark tests against the original touchscreen apparatus using a mutant mouse model (rl-/+) and the NMDA antagonist MK801 known for its effects on cognition and locomotion. This versatile and habitable SmartCage will provide visual-discrimination cognitive testing and enable integration testing of cognition with other aspects of behavior, such as sleep and wake activity, thus shedding light on the interdependence of cognition and other neurobehaviors. Our novel approach is flexible, scalable, and provides a foundation for a high-throughput cognitive assay system to be developed in a Phase II study. 7. PROJECT NARRITIVE Millions of people suffer Alzheimer's disease and other dementias, yet there are no preventive medicines and effective treatments. To develop better therapies, we need better testing technology. Here we propose to develop an automated touchscreen-piezo toolkit for testing drug effects on animal learning and memory effectively, which will complement to and enhance the current cognitive assays.