This project is based on our previous finding that during the prenatal period the majority of neurotransmitter receptors in primates concentrate largely in the developing cortical plate. In sharp contrast, adrenergic receptors concentrate int he transient embryonic laminae, including the marginal, subplate, intermediate and ventricular germinal zones. Furthermore, each of the adrenergic receptor groups (alpha1, alpha2 and beta) has a distinct distribution within these embryonic zones. These observations suggest that noradrenaline is in a unique position to play an important role in the regulation of multiple aspects of cortical formation and that distinct adrenergic receptor subtypes may be involved in regulation of different developmental events. Thus, we are proposing to determine the precise nature (genetically distinct subtypes) of alpha1, alpha2 and beta adrenergic receptors present int he embryonic cerebral cortex of rhesus monkey and identify the cellular elements expressing specific adrenergic receptor subtypes. We will also investigate whether adrenergic receptors of the embryonic cerebral wall have access to their conventional neurotransmitter and, therefore, are in a position to be activated by it. For this purpose, we will evaluate the relationship between the distribution of adrenergic receptors and adrenergic innervation and measure the levels of noradrenaline and its metabolites in the transient embryonic zones of the developing cerebral cortex. Finally, in collaboration with projects I and III, we will initiate studies in in vitro cortical preparations in order to assess the roles of noradrenaline and its receptors in proliferation, migration and differentiation of cortical cells. These studies should significantly enhance our understanding of the role played by the adrenergic system in the formation of the cerebral cortex. They will also pave the way for future detailed functional studies in vivo, as well s for investigations into the interactions between fetal adrenergic and other neurotransmitter systems.
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