Neurobiology

Thomas L. Schwarz, Ph.D.

Professor of Neurology and Neurobiology
(Children's Hospital)

The Schwarz lab has two primary interests: the mechanism of secretion of neurotransmitter at the synapse, and the function of K+ channels in their cellular milieu. Both questions are approached genetically and with a combination of molecular and electrophysiological techniques. To study transmitter secretion, we have used Drosophila and have analyzed mutations in a number of important synaptic proteins including synaptotagmin, syntaxin, and VAMP/synaptobrevin. We are also engaged in an extensive genetic screen for new loci that are important for synaptic function„the recent completion of the sequencing of the Drosophila genome greatly facilitates the molecular characterization of any newly identified genes. These projects have also involved us in questions of membrane trafficking outside the nervous system, particularly in early embryos, and in the mechanisms of axonal transport of organelles. To study the physiological significance of individual K+ channels, we have knocked out the genes for three such channels in mice (Kir2.1, Kir2.2, and Kv4.2). The functional consequences have been investigated in cardiac myocytes, vascular smooth muscle cells, and hippocampal pyramidal cells. By using this genetic approach we can not only identify the molecular nature of in vivo currents and obtain an appreciation of the biophysical role of the channel in the single cell, but can also examine physiology at the level of intact organs and indeed the entire organism. These studies have also involved the lab in an examination of the control of cortical blood flow and in the pathogenesis of cleft palates.