Host: Professor Christian Froekjaer Jensen

Abstract:
Neurons couple to one another at synapses and can track action potentials firing at 100-1000 times a second. How do synapses fire at these rates with high temporal fidelity? And also remain robust under high frequency stimulation? To explore membrane dynamics at synapses we are pursuing a genetic strategy using the nematode C. elegans, and validate our findings in cultured rodent neurons using superresolution fluorescence microscopy, time-resolved electron microscopy, and electrophysiology. 
Exocytosis. Synaptic vesicles dock and are poised to fuse with the plasma membrane. Fusion is initiated by calcium influx into the synapse. The speed of fusion is maintained by tight coupling of synaptic vesicles to calcium channels at docking sites 33 nm, so that calcium reaches the fusion site within microseconds. 
Endocytosis. Synaptic vesicle proteins and membrane must be recovered after fusing to the synaptic membrane. To capture images of endocytosis in a living organism, we combined optogenetics, high-pressure freezing and electron microscopy. We observed that in mouse neurons membrane is recycled within 50 to 300 milliseconds after stimulation. This novel form of membrane recovery is called ultrafast endocytosis, and it allows the synapses to recover synaptic vesicle components to maintain neurotransmission.

Bio:
Dr. Jorgensen received his Bachelor's of Science Degree in Animal Resources from the University of California at Berkeley in 1979. He completed his graduate work with Dr. Richard Garber and received his Ph.D. from the Department of Genetics at the University of Washington in 1981. Postdoctoral work was conducted in H. Robert Horvitz's laboratory at the Massachusetts Institute of Technology where Jorgensen initiated studies into the genetic basis of GABA transmission in the nematode C. elegans. In 1994 Jorgensen established his own laboratory in the Department of Biology at the University of Utah. Jorgensen is currently a Distinguished Professor in the Department of Biology and an Adjunct Professor in the Departments of Human Genetics and Bioengineering. In 2005, Jorgensen was named an Investigator of the Howard Hughes Medical Institute. In 2022 he was elected to the National Academy of Science. Jorgensen has held the position of Visiting Scientist at Charité Universitätsmedizin in Berlin, Germany since 2013. Jorgensen studies the molecular mechanisms of synaptic transmission using the nematode C. elegans and the mouse. His studies have focused on four main areas: neurotransmitters, exocytosis, endocytosis and genome engineering. The Jorgensen laboratory has made several important discoveries in GABA neurotransmission including the identification of the vesicular GABA transporter and a novel excitatory GABA receptor. Jorgensen's laboratory pioneered electrophysiological techniques in C. elegans. Notable results include the demonstration that the SNARE protein syntaxin is required for docking and priming synaptic vesicles, in contrast to previous experiments. Jorgensen's laboratory demonstrated that there is an ultrafast mechanism of endocytosis (50 ms) at C. elegans synapses and at mouse hippocampal synapses. Nonetheless regeneration of synaptic vesicles requires clathrin and the clathrin adaptor complex AP2. He has further demonstrated that AP2 can function as two hemicomplexes. The laboratory has also contributed several new techniques including methods to generate single copy gene insertions, and targeted knockouts in C. elegans. The laboratory has also developed new techniques for microscopy, notably a method to correlate super-resolution fluorescence microscopy with electron microscopy.