This project is a morphologic analysis of the early development of cerebral cortex in the rat: in particular, the development of those elements which comprise neuronal circuitry in the neocortex. The central goal is to analyze the establishment of monoaminergic (MA) projections to neocortex in order to understand their role in cortex development, their contribution to the function of immature cortex and their ultimate place and significance in the circuitry of adult cortex. Using a false transmitter as an electron microscopic marker, our preliminary studies indicate that MA projections are amongst the first to develop and dominate cortical circuitry in the perinatal period. We shall attempt to demonstrate by a light microscopic histofluorescence method those axon terminals which take up catecholamines. We have shown that the ability of the axon plasma membrane to take up neurotransmitter precedes in development the capability to synthesize transmitter; the laminar distribution of axons with endogenous transmitter will be compared with the distribution of axons that can take up but not synthesize transmitter. Midbrain lesions will be used to demonstrate that the axons which take catecholamines arise from MA neurons in the brain stem. Antibodies to catecholamine synthetic enzymes (e.g., DBH, TH) will be used to demonstrate the MA terminal innervation pattern in adult and immature neocortex, using immunohistochemical methods (both immunofluorescence and PAP). Finally, the posssible trophic influence of MA projections upon cortex development will be studied using the barrel field of the mouse as a model system. We shall determine if MA input is essential for normal barrel development and if lesions of the MA neurons influence the normal formation of barrels and of their thalamic input.