Project: Research project

Project Details


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.
Effective start/end date9/10/838/31/86


  • National Institutes of Health


  • Medicine(all)
  • Neuroscience(all)


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