Imaging Voltage with Microbial Rhodopsins

Membrane potential is the critical parameter that reflects the excitability of a neuron, and it is usually measured by electrophysiological recordings with electrodes. However, this is an invasive approach that is constrained by the problems of lacking spatial resolution and genetic specificity. Recently, the development of a variety of fluorescent probes has made it possible to measure the activity of individual cells with high spatiotemporal resolution. The adaptation of this technique to image electrical activity in neurons has become an informative method to study neural circuits. Genetically encoded voltage indicators (GEVIs) can be used with superior performance to accurately target specific genetic populations and reveal neuronal dynamics on a millisecond scale. Microbial rhodopsins are commonly used as optogenetic actuators to manipulate neuronal activities and to explore the circuit mechanisms of brain function, but they also can be used as fluorescent voltage indicators. In this review, we summarize recent advances in the design and the application of rhodopsin-based GEVIs.

Automated summary

Membrane potential, a critical parameter reflecting neuron excitability, is traditionally measured invasively by electrodes, but new fluorescent probe technologies offer high spatiotemporal resolution for individual cell activity. Genetically encoded voltage indicators show superior performance in accurately targeting genetic populations and revealing neuronal dynamics. Microbial rhodopsins, commonly used in optogenetics to manipulate neuronal activities, can also serve as fluorescent voltage indicators, with recent advances in their design and application summarized in this review.