STRIATAL GLUTAMATE RECEPTORS DURING DEVELOPMENT

本应用程序提出了一系列的实验来研究

This application proposes a series of experiments to investigate the development of striatal glutamate receptor subtypes in the rat and cat brain. The striatum is known to participate in the planning and execution of movement, and more recently has been found to play a role in cognition, learning, and behavior. Structurally, the striatum is comprised of at least two compartments, the patches and the matrix, which share afferent and efferent connections. The existence of two parallel but distinct circuits provides a capacity for integration and modulation of information both to and from the striatum. To date, the patch and matrix compartments have been defined primarily by immunohistochemical and autoradiographic techniques. The patches appear in the striatum earlier than the matrix, and they are richer in opiate receptors and dopamine than the surrounding matrix. Acetylcholinesterase (AChE) activity is higher in patches than in matrix in fetal and noenatal rat and cat, only to reverse the pattern during aging. The adult rat and cat exhibit AChE-poor patches and AChE-rich matrix. Glutamate is the neurotransmitter of the cortical projections to the striatum, and there is preliminary evidence using quantitative in vitro autoradiography to suggest a patchy distribution of striatal glutamate receptor binding in neonatal rat, adult cat, and in infant and adult human brain. The subtype of glutamate receptor defined by the binding of the excitatory amino acid (EAA) N-methyl-D-aspartate (NMDA) has been shown to have a trophic effect in cortical neuronal development, but has not been investigated in the striatum. To determine the pattern of development of striatal glutamate receptors, neonatal rat and fetal kitten brain will be utilized. Quantitative in vitro receptor autoradiography will be used to determine the time course of appearance of the patch-matrix mosaic of receptor binding of the glutamate receptor subtypes (NMDA, iontrophic quisqualate, metabotropic quisqualate, and kainate). Adjacent brain sections will beassayed for AChE activity to compare the patch-matrix mosaic defined by EAA autoradiography to the mosaic defined immunohistochemically. Finally, lesioning experiments will be done to determine the effect that cortical and nigral connections have on the development of the patch- matrix mosaic of EAA receptors. Neonatal rats and kittens will undergo decortication, and fetal kittens will undergo chemically induced nigral lesions with 6-hydroxy dopamine, followed by receptor autoradiography. These manipulations will provide information regarding the role that cortical and nigral connections to the striatum play in the development of the patch-matrix mosaic.