My laboratory studies ion channels gated by glutamate receptors. In the vertebrate CNS, glutamate receptors in the postsynaptic membrane underlie the transmission of information at excitatory synapses. Our goal is to provide a better understanding of synapses by determining the properties of glutamate receptors and of the channels that they control. We use electrophysiological recordings to study the activation and desensitization of the receptors following rapid application of glutamate. We also study compounds that block the glutamate binding site or physically occlude the ion pore. More recently, we have concentrated on a subtype of glutamate receptor that exhibits a unique form of desensitization. Comparison of the different receptor subtypes should lead to a clearer picture of how the binding of glutamate operates the channels.

A second major goal of my lab is to understand the control of neuronal differentiation. We study the properties of neurons derived from human and mouse Embryonic Stem (ES) cells. We have shown that mouse ES-derived neurons express voltage-gated Na, K, and Ca channels, as well as channels gated by glutamate, GABA and glycine. Within two to three weeks after induction, some of the cells form excitatory synapses, whereas others form inhibitory connections. Using antibodies GAP43 and MAP-2 we have demonstrated the segregation of these proteins into separate axonal and somatodendritic compartments. In both their physiological properties and their ability to establish a polarized phenotype the differentiated mouse ES cells strongly resemble neurons from the CNS. Studies of human ES cell differentiation are ongoing.

• Lab Website