ROLE OF EXCITATORY AMINO ACIDS IN CORTEX DEVELOPMENT

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The long term objective of this research is to understand the role that excitatory amino acid transmitters (EAAs) play in cortical morphogenesis and plasticity. The receptors that mediate the actions of EAAs are present in the developing brain and have been shown to play a role in models of learning and memory and in developmental plasticity. The proposed experiments will examine the role of EAA receptors in the normal development of rodent barrel field cortex and their role in the structural reassignment of cortex which occurs after neonatal peripheral deafferentation. The specific aims are 1) to characterize the ontogeny of EAA receptors in the whisker (peripheral input) to barrel (cortex) pathway, 2) to determine whether changes in EAAs caused by neonatal administration of EAA receptor antagonists will alter barrel formation, 3) to determine whether neonatal administration of the serotonergic neurotoxin, PCA, delays the development of EAA receptor expression in the whisker to barrel pathway, 4) to determine whether neonatal whisker removal, which deafferents the cortex, will alter the ontogeny of EAA receptors and 5) to determine whether modification of EAA systems by EAA receptor antagonists will alter the structural reassignment of cells and afferents which normally occurs after deafferentation. EAA receptors will be visualized by in vitro receptor autoradiography and immunocytochemistry. The consequences of EAA antagonists and 5HT neurotoxin treatments and of whisker removal on barrel formation will be assessed in terms of changes in size and cytoarchitecture, in patterns of thalamic and non-thalamic (5-HT) afferents and in the density and distribution of EAA receptors. The developing whisker to barrel pathway will serve as a model for examining the role of EAAs in the reorganizational changes which occur after peripheral injury. Since sensory information from the peripheriphery is likely conveyed by EAAs, the characterization of the role of EAA receptors in the establishment of peripheral maps in the cortex is potentially clinically important. By understanding the neurotransmitter control of map formation, it may be possible to design strategies to enhance recovery after injury.