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The physiological basis of neuronal toxicity caused by various insults including excitatory amino acids, oxidative stress and cerebral ischemia is being studied using quantitative imaging techniques, confocal microscopy, genetic approaches in model organisms, and molecular approaches in cultured cell lines, cultured primary neurons and in intact animals. These studies aim to develop an understanding of the mechanisms of neuronal injury in acute and chronic disorders. The regulation of the expression of voltage-gated ion channels in cell lines and primary cultures is being studied by molecular and patchclamping techniques. In addition, molecular genetic, electrophysiological and cell biological approaches are being used to explore the relationships between neurotransmitter transporter structure, substrate transport, inhibitor binding and ion permeation. New quantitative imaging approaches are being used to study the basic processes of neuropeptide secretion. Investigators in the Molecular Pharmacology program are also examining the mechanisms of autonomic regulation and synaptic transmission of the urogenital system. These studies include neuroanatomical and neurophysiological research aimed towards the development of agents to modulate neuronal control of the urinary bladder, colon, and sex organs. Targeted disruption of GABA receptors is being used as a tool to investigate the function of these receptors and their specific components in transgenic mice. The mechanism of action of anesthetics is being studied in genetic model organisms and using techniques of magnetic resonance spectroscopy.