This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Knowledge of cerebral cortical connectivity in primates is essential for understanding higher brain mechanisms of sensation, perception and cognition and their disorders but connection tracing studies are increasingly uncommon, older studies are accessible only through publications which represent an earlier investigator's interpretation of the data, and access to the original data for re-interpretation is commonly unavailable. Retrieval of archives of experimental material and conversion to an accessible digital form presents considerable logistical and other handicaps. We seek to develop a comprehensive and ongoing archive of material demonstrating cortical and subcortical connectivity in rhesus monkey brains, in which all the histological material from individual experiments is available in its digital form, with a suitable search engine providing open access to all investigators. In this way, original experimental data can be annotated and re-interpreted as newer parcellations of cortical and subcortical structures are made on the basis of accumulating functional and clinical data. The current proposal builds on expertise in constructing high resolution microscopic atlases of primate brain architecture and will create a searchable database of connections of the cerebral cortex in the adult rhesus monkey. A pipeline will be established in which targeted cortical areas in a series of monkeys will be injected with a tracer transported both retrogradely and anterogradely. Digital data about each individual brain will be collected by means of: structural mri;serial imaging of the sectioned blockface as each 40?m section is removed during sectioning of the brain;imaging at high resolution of alternate sections through the brain stained for the transported tracer or stained with the nissl stain;warping images of the sections back onto the blockface images of the brain and mris to provide a 3d volumetric dataset for each brain. The searchable database into which the individual datasets will be stored will incorporate a capacity to annotate the dataset from each experimental brain in relation to a standard high resolution digital atlas of the rhesus monkey brain, a capacity for making queries about connections by name or by visual inspection of injected regions or of likely sources of afferents and targets of efferents, a capacity for interoperability with databases of other relevant neuroscience information. The database will also permit incorporation of datasets of connectivity drawn from material in publications and/or existing slide. The result will be a living archive to which data essential for the understanding of the pathophysiology of neurological and neuropsychiatric disorders can continue to be added and queried.
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