When I joined the lab, Dr. Ryan’s group had recently published a seminal paper showing that neuronal activity in nerve terminals drives ATP synthesis. Despite its relevance to brain function, it was not clear what mechanisms account for activity-driven upregulation of glycolysis. The clue to solving this puzzle came from previous studies demonstrating neuronal expression of the glucose transporter GLUT4, which in muscle is regulated by insulin and contraction. I discovered that as in exercising muscle, action potential firing drives the insertion of GLUT4 to presynaptic endings, and neurons strictly rely on this glycolytic regulatory system to sustain their function. This metabolic module has important implications for brain function, and it may also explain why neuronal activity declines rapidly during ischemic attacks and acute hypoglycemia. To further characterize glucose uptake and glycolytic flux in presynaptic endings, I am currently using a novel optical sensor for glucose, Sweetie, developed by Dr. Loren Looger’s group at Janelia. This sensor allows for real-time monitoring of glucose levels in presynaptic boutons in response to stimuli such as electrical activity or changes in extracellular glucose. This work will form the foundation for future studies investigating how glucose handling may be dysregulated in cognitive impairments that occur in metabolic diseases such as diabetes.
Friday, September 7, 2018 at 4:00pm to 5:00pm
Icahn School of Medicine at Mount Sinai, Hess Seminar Room B
One Gustave L. Levy Place New York, NY 10029-6574