Mitochondrial delivery is essential for synaptic potentiation

Author Posting. © Marine Biological Laboratory, 2007. This article is posted here by permission of Marine Biological Laboratory for personal use, not for redistribution. The definitive version was published in Biological Bulletin 212 (2007): 169-175.Mitochondria, as portable generators that power synaptic function, regulate the ATP supply and calcium homeostasis in the neuron. As molecular interactions within the synapses before and after the potentiation are beginning to be elucidated, the deciding moment during the tetanic stimulation that gives rise to the strengthening of the synapse remains a mystery. Here, I recorded electrically from an intact Drosophila nervous system, while simultaneously using time-lapse confocal microscopy to visualize mitochondria labeled with green fluorescent protein. I show that tetanic stimulation triggers a fast delivery of mitochondria to the synapse, which facilitates synaptic potentiation. Rotenone, an inhibitor of mitochondrial electron transport chain complex I, suppresses mitochondrial transport and abolishes the potentiation of the synapse. Expression of neurofibromin, which improves mitochondrial ATP synthesis in the neuron, enhances the movements of mitochondria to the synapse and promotes post-tetanic potentiation. These findings provide unprecedented evidence that the mitochondrial delivery to the synapse is critical for cellular learning.This project is supported by Grass fellowship awards (2004, 2006) to J.T. and NIH funding AR47752-01A1