The NMDA receptor, a subclass of the neurotransmitter glutamate receptors, is widely present at synapses in the vertebrate central nervous system. NMDA receptors have been implicated in the process of long term potentiation, a model of learning and memory, and synapse formation and stabilization. The long term objective of this research is to understand the mechanisms of operation of synaptic ion channels, particulary, the processes of ligand binding and channel gating. The immediate goal of the research is to examine the activation mechanisms of synaptic receptors stimulated by glutamate. By applying kinetic analyses, Dr. Auerbach will be able to investigate how agonists, glutamate- like molecules, activate NMDA ion channels, regulate the gating of channel pores and the desensitization of NMDA receptors. In addition, the developmental changes in NMDA activated channels will be studied. The Principal investigator has developed a method of applying agonist by diffusion through the back of a pipette, a powerful technique which will enable the PI to obtained data from a single channel over a range of concentrations. Experimentally, this approach will allow for the study of ligand activated channels in their native cellular environment. Results of this investigation will contribute to the understanding of the mechanisms of how the glutamate neurotransmitter operates and will provide a microscopic description of synaptic transmission.
