NEURON DEATH IN CENTRAL NERVOUS SYSTEM DEVELOPMENT

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The nature of the intrinsic organization of the neocortex is a central question in developmental neurobiology. The mature neocortex is a mosaic of functionally and anatomically specialized areas that share a fundamental laminar and columnar structure. The central question is whether the neocortex is an unspecified, unified structure on which local identity is imposed by an external agency like the thalamus or whether it contains intrinsic local identity that attracts and organizes particular input structure and specifies certain output. The development of the tangential and laminar specificity of thalamic projections to the cortex will be investigated in two experimental conditions. In the first experiment, a region of dorsal neocortex, principally visual cortex, will be removed in utero prior to the arrival of the first thalamic axons in the cortex, and the development, survival, mature projection pattern and volume of arbor of thalamic axons will be investigated. In the second manipulation, a developmental deletion of the layer IV and varying amounts of the supragranular layers will be made using a mitotic inhibitor, MAM (methylazoxymethanol acetate), with a parallel analysis. The intent of both of these manipulations is to delete the target population prior to any interaction of axon and target populations, and thus reveal any intrinsic specificity in the choice of cortical and laminar terminal area by incoming thalamocortical axons, and the mechanisms of population matching between the thalamus and cortex. The clinical significance of this work is direct: in addition to supplying basic information about the nature of cortical reorganization after brain damage, we will be directly describing what happens to the cortex after early local deletions, such as might happen with a vascular accident, or after a cytotoxic insult.