We are requesting funds to establish an advanced live cell imaging system at the Harvard NeuroDiscovery Center (HNDC) Optical Imaging Core (OIC). The HNDC is a community of researchers from across the broader Harvard community, including Harvard Medical School (HMS) and its eighteen affiliated teaching hospitals throughout the greater Boston area. Members of the HNDC are interested in both basic and applied neuroscience research that provides insight into the causes, prevention and treatment of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, ALS and Multiple Sclerosis. The HNDC Optical Imaging Core collaborates with and serves over 100 research groups from across our community;the majority of which are funded by PHS programs. Despite providing a range of advanced optical imaging and image analysis services, the Center's Optical Imaging Core has a very limited live cell imaging capability (consisting of slit- based Olympus DSU unit, Arc-lamp light sources and a small stage incubator). Many of our users seek access to a high performance live cell imaging system. After extensive research and discussion with our users, we have designed a unique live cell imaging setup that builds on our existing Olympus Disk Spinning Unit (DSU) - IX81 microscope system. The upgrade includes a high performance Andor Revolution XD confocal system with the Yokogawa CSU- X1 scanner unit, multiple laser excitation lines, and essential live cell imaging accessories. By building upon our existing platform (and avoiding the need to purchase a new microscope body), this proposed design addresses the major issues raised by our users in a cost-effective way. Furthermore, by combining the Olympus DSU with the Yokogawa CSU-X1 scanner unit, we will provide a live cell imaging capability beyond that of any commercially available off-the- shelf confocal system. Establishing such a versatile, high-performance live cell imaging system will have an enormous impact on the research of our very broad PHS-funded user group.