Project Summary / Abstract Dementias from Alzheimer’s disease (AD) and age-related cognitive impairments are a major health and socio- economic concern in the US and worldwide. AD remains resistant to treatment based on earlier research efforts. Approximately 20% of the US population will be 65 or older by year 2030; roughly 8 million of these individuals are expected to suffer from AD. The neural circuit aspects of AD are an emerging new research area with tremendous potential for growth and progress. The UC Irvine Center for Neural Circuit Mapping (CNCM) research program has quickly established strong federal funding that supports our transformational projects with significant clinical translational potential. The ongoing acceleration of our understanding of the nervous system will drive the development of new therapeutic strategies to treat AD and other brain diseases over the next decades. Our new CNCM research program has unified multidisciplinary investigators from multiple academic units across UC Irvine including the Schools of Medicine, Biological Sciences, Pharmacy and Pharmaceutical Sciences, Engineering, and Information and Computer Science. Our T32 program is designed to train the next generation of researchers focused on neural circuit studies of brain disorders including AD and related dementias. The proposed training program will be administered by the CNCM and will be supported by CNCM investigators who have fostered a highly collaborative environment exemplifying interdisciplinary team-based research. Our exciting and diverse group of faculty members will mentor and support predoctoral and postdoctoral trainees in neural circuit studies using a range of interdisciplinary approaches combining analysis of mouse genetic models and post-mortem human brain tissues with state-of-the-art technologies that include viral genetic mapping, in vivo neural ensemble recording/imaging, single-cell genomics, engineering and computational modeling. Our faculty mentors and trainees will expand our mechanistic understanding of Alzheimer’s disease and other disorders and develop tools that enable early detection and diagnosis. Our training plan is well defined; trainees are required to take courses and seminars related to cutting-edge neuroscience and AD research with a neural circuit focus. We anticipate four trainees per year (2 pre- and 2 postdocs) whose training will continue until they complete their respective programs. Critically, we will teach our trainees to develop their own unique tools and methodologies to address scientific questions that others cannot. We include training in rigor and reproducibility, statistics and data analysis training, and professional development. The expected outcome of our T32 program is to establish a successful training pipeline to prepare trainees with career-long experimental and quantitative skills as future research leaders who will focus on neural circuit analysis of Alzheimer’s disease and related demen...