The proposed work is both a continuation and an extension of the studies that we have been engaged in for some years. The longterm objectives of this work are to provide as complete an analysis of the organization and development of the hippocampal formation as possible, and, by taking advantage of the unusual simplicity of these cortical areas, to provide a model for understanding the development of cortical areas in general. In the coming grant period we plan to focus our attention on several specific problems associated with the development of the dentate gyrus, the structural organization of which is sufficiently well known (in large part from our own earlier studies) to enable us to address a number of fundamental questions concerning cortical development. These include: (1) Analyzing in detail three-dimensional morphology of individual dentate granule cells to establish on a quantitative basis the degree of variability in such cells; (2) Examining, again quantitatively, the development of these neurons both in vivo and in vitro; (3) To determine, using a variety of immunocytochemical procedures, the unusual pattern of migration of the dentate granule cells; (4) To reexamine the origin of the glial cells in the dentate gyrus; (5) To examine the role played by the so-called nerve cell adhesion molecule (nCAM) in the assembly of the dentate gyrus and in the initial formation of its connections; and (6) To use the dentate gyrus to screen for the expression of a variety of cellular oncogenes during normal development, and to determine if some of these genes are reactivated during the reactive synaptogenesis that occurs in the dentate when it is deprived of certain of its afferent inputs.
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