NEUROCHEMICAL CORRELATES OF CEREBELLAR DEVELOPMENT

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Neurotransmitter receptors for acetylcholine, gamma-aminobutyric acid, noradrenaline, serotonin and histamine in the cerebellar cortex of the mouse will be visualized by light-microscopic autoradiography of receptor-bound ligands. The localization of the receptors to regions and/or layers of the cerebellar cortex during postnatal development will be studied with special emphasis on the developmental stage at which receptors first appear. We will attempt to correlate the appearance of receptors with other known ontogenetic events, such as cell migration and synapse formation. MIce with genetic mutations affecting the structure, organization and development of the crebellar cortex will be used in studies aimed at elucidating the cellular localization of neurotransmitter receptors and/or any abnormalities in their normal pattern of development. to determine to what extent receptor appearance and localization is governed by the orderly structure and connections of the cerebellar cortex, cells from the rat cerebellum will be grown in dispersed cell culture and receptors visualized by autoradiography of receptor-bound ligands at various developmental stages. The stage of cerebellar development in culture at which receptors become "functional" will be studied by the autoradiographic localization of changes in 2-deoxy-D-glucose utilization following administration of receptor agonists. Monoclonal antibodies, directed against cell surfaces of rat cerebellar neurons will be raised in mice to obtain reagents necessary for the identification of neuronal cell types in culture. These neurochemical studies could lead to a better understanding of malfunctions affecting the nervous system.