Kathy Engisch

Our laboratory uses highly specialized electrophysiological measurements in combination with genetic manipulations of individual synaptic proteins, to study the basic mechanisms of neurotransmitter release and its modulation. Neurotransmitter release shows dramatic activity-dependent behaviors. Rapid repetitive stimulation can cause an increase in release, called facilitation, in some nerve terminals. In others, the same protocol can cause depression, or a decrease in release. These types of short-term plasticity are essential for information processing in the brain, but the underlying mechanisms are unknown. We have recently found that expressing a mutant form of the synaptic vesicle protein Rab3A in adrenal chromaffin cells can greatly increase activity-dependent depression. We are currently studying the characteristics of neurotransmitter release in a Rab3A mutant mouse. We are also interested in longer term regulation of neurotransmitter release by activity. In collaboration with Mark Rich's laboratory, we have found that block of activity causes increases in synaptic strength by increasing the number of vesicles that fuse, and the size of the individual release events. We are currently examining the role of particular synaptic proteins in this long term plasticity.
In the laboratory, we study neurotransmitter release in two very accessible, simple preparations. At the mammalian nerve-muscle synapse, we use two electrode voltage clamps to record acetylcholine-activated currents in individual muscle fibers. In a neuroendocrine cell from the adrenal gland, we use perforated patch clamp to record tiny increases in the cell capacitance that occur when vesicle membrane adds to the plasma membrane surface area. We also use carbon fibers to detect released norepinephrine and epinephrine from individual adrenal chromaffin cells. These data are supplemented by imaging of intracellular calcium levels using fluorescent calcium-sensitive dyes.