Advances in microscopy and fluorescent probes have revolutionized biological research by enabling the normally colorless world of the cell to be visualized in high spatiotemporal resolution and with vivid colors. Such approaches have provided many ground-breaking insights in cell biology. In the field of neuroscience, researchers have developed a range of fluorescent indicators: genetically encoded pH indicator (GEPI), genetically encoded transmitter indicator (GETI), genetically encoded voltage indicator (GEVI) and genetically encoded calcium indicator (GECI). However, visualization of the most fundamental cellular process – how a cell metabolizes sugars to produce biological energy – has been hampered by a lack of high-performance optogenetic indicators.<br/>     Neurons in the brain have a high demand for energy, and this demand further increases when the neurons are activated. The Astrocyte-Neuron-Lactate-Shuttle model postulates that astrocytes (non-neuronal brain cells) produce lactate and this pool of lactate serves as a reservoir of energy that is shuttled to neurons when they are activated and need of energy. Growing evidence suggests that changes in this lactate shuttle play a key role in neurodegenerative diseases and psychiatric disorders. Here, we report a new class of indicator, iLACCO1, a genetically encoded metabolite indicator (GEMI). iLACCO1 enables to detect a change in the concentration of lactate in an intensiometric manner. The indicator is a powerful tool for better understanding the neural metabolism lactate is involved in.

Development of a genetically encoded intensiometric lactate indicator iLACCO1

2019 Fall National Meeting

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