Abstract
A holy grail in neuroscience is to understand how brain functions arise from neural network-level electrical activities. Voltage imaging allows for the direct visualization of electrical signaling at high spatial and temporal resolutions across a large neuronal population. Central to this technique is a palette of genetically-encoded fluorescent probes with fast and sensitive voltage responses. In this review, we chronicle the development and applications of genetically-encoded voltage indicators (GEVIs) over the past two decades, with a primary focus on the structural design that harness the power of fluctuating transmembrane electric fields. We hope this article will inform chemical biologists and protein engineers of the GEVI history and inspire novel design ideas.
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