The goal of this study is to examine the mechanisms by which early experience is encoded into olfactory-limbic circuitries during development. The experiments start from the perspective of the basic properties of NMDA receptor complex and work toward the investigation of possible learning mechanisms. This approach was selected with the design that an understanding of the biochemistry of this receptor system during development will provide necessary baseline data to develop and test hypotheses about the role of this receptor complex in the encoding of experience into specific neural circuits. In the proposed experiments we will examine the developmental regulation of components of the NMDA receptor complex, its recognition site(s) its allosteric regulatory site, and its coupling to phoshoinositide metabolism. Parallel electrophysiological experiments will be pursued to test the hypothesis that NMDA receptors have a greater involvement in early development at times coincidence with the encoding of stimuli into developing circuitries. Initially we will focus on the hippocampus, since this structure contains a high density of NMDA receptors and is known to be a key processing center for learning and memory. In the later phases of the study we will extend our experimental system to include the olfactory bulbs as a model of peripheral sensory input to the hippocampus. The olfactory system was chosen because its connections are only three synapses from the hippocampus and NMDA receptors have been shown to participate in early olfactory learning. The combination of this experimental system and a multidisciplinary approach of biochemistry, autoradiography and electrophysiology will permit the processes of early learning to be carried out at a comprehensive level not previously possible.
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