Over the last 20 years many neuroregulators have been identified and significant progress has been made in identifying the molecular basis of neurotransmission. The in vivo dynamics of several neurochemical events have been monitored using amperometric microelectrodes, but this approach is hindered by the relatively poor selectivity of these electrodes. In the proposed project, electrodes with excellent selectivities will be developed by incorporating a thin layer of immobilized enzyme and other protective coatings into the microelectrode. Such electrodes would allow the in vivo determination of non-electroactive species for the first time. Initially, an electrode for the determination of the potent neuroexitatory amino acid, glutamate, will developed, since it has been identified in many neuronal pathways and is normally present in fairly high concentrations. The spacial, temporal and analytical characteristics of the electrodes will be improved, and microelectrodes for other compounds important in neuroregulation will be developed in Phase II.