Abstract
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.
Highlights
Probing functional neural circuits at high spatiotemporal resolution is crucial for understanding how neuronal populations work together to generate behavior
Since somatic calcium influx is coupled with action potentials (APs), the activity of large numbers of neurons can be monitored simultaneously using calcium imaging as an indirect measurement of neuronal firing with an excellent signal-to-noise ratio (SNR) (Yuste and Katz, 1991; Grienberger and Konnerth, 2012)
Arch- and Mac-based positive-going eFRET Genetically encoded voltage indicators (GEVIs) have been developed by modifying the natural proton transport pathway within microbial rhodopsins (Abdelfattah et al, 2020)
Summary
Probing functional neural circuits at high spatiotemporal resolution is crucial for understanding how neuronal populations work together to generate behavior. Optical imaging with genetically encoded indicators can overcome these drawbacks and monitor the activity of large numbers of neurons simultaneously. Kralj and colleagues developed a new type of GEVI based on microbial rhodopsins and their fluorescence.
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