Studies in the Laboratory of Cellular and Molecular Neurophysiology focus on the receptors and ion channels that mediate signalling in the central nervous system. Excitability in the brain takes many forms. On the millisecond time scale, cells fire action potentials and communicate via activation of ligand-gated ion channels at excitatory and inhibitory synapses. Intimately linked to signalling on this fast scale are second messenger systems that control a wide range of metabolic processes. Ultimately, changes in activity mediated by a vast network of electrical and biochemical processes are tied to the regulation of gene expression itself. Such regulation underlies our creative abilities to rationalize thoughts, experience emotions, and recall memories. Our experiments target glutamate receptor ion channels, the molecules mediating the initial response at excitatory synapses. The atomic resolution of ion channel structure made possible by crystallography and x-ray diffraction, combined with results from physiological and biochemical approaches, has made it possible for the first time to propose molecular mechanisms underlying activation and desensitization for glutamate receptor ion channels. By extending this approach, we hope to gain insight into the molecular basis for the behavior of individual glutamate receptor subtypes.