NMDA and metabotropic glutamate receptors have been shown to play a role in the activity-dependent formation of synaptic circuitry during critical periods of brain development. Lead interactions with glutamatergic signaling also have been demonstrated and these effects may alter synaptic connectivity and produce permanent impairments in the brain function. The proposed studies focus primarily on the use of a well- established model of cortical development, the somatosensory barrels, to test the hypothesis that lead-induced changes in the glutamate receptors alter activity-dependent development of cortical circuitry. The proposed studies consist of (1) examination of the effects of low-level lead exposure on the temporal and spatial expression of glutamate receptor and glutamate receptor mRNA in the cortical barrel field, hippocampus and cerebellum; (2) examination of the effects of lead exposure during different periods of development on glutamate receptor expression in the barrel fields, hippocampus and cerebellum; and (3) examination of the effects of lead exposure on cortical barrel plasticity changes induced by neonatal whisker removal. To achieve the stated aims of this project, glutamate receptor expression will be evaluated by this project, glutamate receptor expression will be evaluated by immunohistochemistry, receptor autoradiography and in the situ hybridization. The overall goal of the project is to provide insight into the impact of lead on activity- dependent processes critical to normal brain development to test the stage for the design for rational intervention strategies.
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