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. ? ? ?
