The studies proposed in this application are directed at the analysis of certain aspects of the morphological development of the dentate gyrus of the hippocampal formation in the rat. The long term goal of this research in an understanding of the mechanisms by which the principal neuronal cell type (the dentate granule cell) of this simple, mammalian cortical structure, develops a mature dendritic configuration and, in turn, receives an appropriate complement of inputs from a variety of afferent systems. We have chosen the dentate gyrus as a model system for the analysis of cortical development because of its relatively simple cytoarchitectonic organization and the rather strict laminar arrangement of its major extrinsic afferents. But we would hope that the principles of organization operating in this simple cortical structure would have widespread applicability to more complex, neocrotical regions. The particular projects we propose are: 1) to carry out a quantitative analysis of the development of the dendritic tree of the dentate granule cell, (2) to study the development of the major afferents of the dentate gyrus, and (3) to survey the development and structure of glial cells in the dentate gyrus. The development of granule cell dendrites will be studied in preparations stained by several variants of the Golgi method and also by direct intracellular injection of horseradish peroxidase into granule cells in the hippocampal slice preparation. In both cases, analysis will be aided by a computer-linked microscopic reconstruction system. The development of the afferents of the dentate gyrus will be studied with the retrograde tracer, wheat germ agglutinin-conjugated horseradish peroxidase, and with 3H-amino acid autoradiography for anterograde studies. The survey of glial development will be carried out both in Golgi preparations and with the immunohistochemical localization of astrocytes with antibodies directed against glial fibrillary acidic protein. The hippocampal formation has long been implicated in processes dealing with memory consolidation and, in pathological cases, with epilepsy. This region appears to be particularly sensitive to birth traumas such as anoxia and is often damaged as a result of neonatal febrile convulsion. By gaining an understanding of the normal development of neuronal form and connections in the hippocampal formation we may get some insight not only into the mechanisms underlying its normal function, but also the means by which genetic and environmental perturbations cause developmental defects.
Showing the most recent 10 out of 14 publications
