Scientific Core (Core Leaders, Clark and Ebner) will provide neuropathological, neuroanatomical and invivo optical imaging expertise required for each project and for the overall Program. Dr. Clark is uniquelyqualified for this role, given his many years of experience investigating neurodegenerative disorders usingboth human autopsy specimens and murine models of human disease. Specifically, the core will investigatethe overall brain architecture, specific areas of degeneration, and specific cellular changes in autopsyspecimens from DM subjects studied or contacted through Project 3, from the CCUG- and Mbnlloverexpressionmurine models of Project 1, and from the Mtm/lAE3/AE3 and Mbnll-'- mice of Project 2, usingroutine 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 humanand murine neuroanatomy, will help in correlating the imaging and pathological findings, and in focusinginvestigations in all three Projects. Dr. Tim Ebner, an innovative neuroscienctist and cerebellar physiologisthas developed a state of the art, system for optically measuring cerebellar circuits, in vivo. The preliminarydata presented in this application are significant not only for their potential to inform us on the pathology ofDM but also because Dr. Ebner's imaging methods for the first time allow studies of LTP in vivo. The specificspecific focus of the core will be: Focus 1 The Core will provide neuropathological characterization ofpatients who have died with myotonic dystrophy types 1 and 2 (DM1 and DM2); Focus 2 ~ The Core willprovide neuropathological characterization of central nervous system pathological changes in transgenicanimals used to model different aspects of myotonic dystrophies; Focus 3 The Core will procure andpreserve tissue for biochemical studies from CNS and other organs of DM1 and DM2 subjects undergoingautopsy examinations; Focus 4 The Core will provide the central facilities and expertise for functional invivo optical imaging of the cerebellar cortex for the murine models of myotonic dystrophy.
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