Scientific Core (Core Leaders, Clark and Ebner) will provide neuropathological, neuroanatomical and in vivo optical imaging expertise required for each project and for the overall Program. Dr. Clark is uniquely qualified for this role, given his many years of experience investigating neurodegenerative disorders using both human autopsy specimens and murine models of human disease. Specifically, the core will investigate the overall brain architecture, specific areas of degeneration, and specific cellular changes in autopsy specimens from DM subjects studied or contacted through Project 3, from the CCUG- and Mbnlloverexpression murine models of Project 1, and from the Mtm/lAE3/AE3 and Mbnll-'- mice of Project 2, using routine histological, immunohistological, and RNA or DNA fluorescent in-situ histological methods. Dr. Clark's extensive experience with both human and murine neurodegeneration, and his knowledge of human and murine neuroanatomy, will help in correlating the imaging and pathological findings, and in focusing investigations in all three Projects. Dr. Tim Ebner, an innovative neuroscienctist and cerebellar physiologist has developed a state of the art, system for optically measuring cerebellar circuits, in vivo. The preliminary data presented in this application are significant not only for their potential to inform us on the pathology of DM but also because Dr. Ebner's imaging methods for the first time allow studies of LTP in vivo. The specific specific focus of the core will be: Focus 1 ? The Core will provide neuropathological characterization of patients who have died with myotonic dystrophy types 1 and 2 (DM1 and DM2);Focus 2 ~ The Core will provide neuropathological characterization of central nervous system pathological changes in transgenic animals used to model different aspects of myotonic dystrophies;Focus 3 ? The Core will procure and preserve tissue for biochemical studies from CNS and other organs of DM1 and DM2 subjects undergoing autopsy examinations;Focus 4 ? The Core will provide the central facilities and expertise for functional in vivo optical imaging of the cerebellar cortex for the murine models of myotonic dystrophy.
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