Excitatory amino acids and their receptors play many important physiological roles in the central nervous system. They are involved in brain development, neural plasticity, memory acquisition, and excitotoxicity. The goal of this project is to determine the mechanisms responsible for transcriptional control of the NMDA subtype of glutamate receptor genes. Promoter regions of the genes from several family members were cloned. Similarities were found in gene structure and transcriptional control elements. NGF activates expression of the NMDAR1 gene via its high affinity Trk A receptor and this activation requires the presence of both Sp1 and GSG transcriptional elements in the proximal promoter region. Over-expression of NGFI-A, also induced by NGF, activates NMDAR1 gene expression suggesting a signal transduction pathway for gene activation involving immediatae early genes.