The Children?s National Medical Center (CNMC), in collaboration with the George Washington University School of Medicine and Health Sciences (GWU), and Georgetown University Medical Center (GU), proposes to develop a Mental Retardation Research Center (MRRC). This center will focus on cellular aspects of brain development and dysfunction and molecular basis of genetic diseases causing mental retardation and developmental disabilities. A total of 38 faculty members will be affiliated with the MRRC as Center Associates or Center Staff. These faculty members represent 15 departments from the collaborating institutions. There will be five cores and a new program development project. The proposed Director of the MRRC, Mark L. Batshaw, M.D., was previously the founding Director of the Children?s Hospital of Philadelphia MRRC (1990-1998). He will also direct the Administrative Core that will serve as the editorial office of the MRRC supported journal Mental Retardation and Developmental Disabilities Research Reviews, as well as functioning as the hub of the Center, providing strategic planning, financial oversight and administrative services to cores and users. A Cellular Neuroscience Core will focus on classic neuropathology (light and EM), immunohistochemistry, and innovative techniques such as confocal microscopy and in situ hybridization technology. A Molecular Genetics Core will provide access to and training in advanced molecular biologic technologies including expression microarrays, quantitative PCR, and automated DNA sequencing. A Neuroimaging Core will provide access to structural and functional brain imaging and image processing and analysis for both animal and human studies. Finally, a Study Design and Statistical Analysis Core will assist investigators in study development, use of statistical methodology, and data storage management and analysis. Also proposed is a New Program Development Project whose principal investigator JoAnne Natale, M.D., Ph.D., seeks to determine if there are fundamental differences in the molecular pathways that produce apoptotic neuronal death as a function of brain maturity. She plans to use all of the research core services within the MRRC. The investigators expect to enhance research productivity in mental retardation and developmental disabilities with the support of this MRRCs.