Abstract

SUMMARYImaging voltage using fluorescent-based sensors could be an ideal technique to probe neural circuits with high spatiotemporal resolution. However, due to insufficient signal-to-noise ratio (SNR), imaging membrane potential in mammalian preparations is still challenging. In recent years, many genetically encoded voltage indicators (GEVIs) have been developed. To compare them and guide decisions on which GEVI to use, we have characterized side by side the performance of eight GEVIs that represent different families of molecular constructs. We tested GEVIs in vitro with 1-photon imaging and in vivo with 1-photon wide-field imaging and 2-photon imaging. We find that QuasAr2 exhibited the best performance in vitro, whereas only ArcLight-MT could be used to reliably detect electrical activity in vivo with 2-photon excitation. No single GEVI was ideal for every experiment. These results provide a guide for choosing optimal GEVIs for specific applications.

Highlights

  • Probing functional neural circuits at high spatiotemporal resolution is crucial to understanding how neuronal populations work together to generate internal brain states and behavior

  • Because somatic calcium influx is directly coupled with action potentials (Smetters et al, 1999), the activity of large numbers of neurons can be monitored simultaneously using calcium imaging as an indirect measure of neuronal firing with excellent signal-to-noise ratio (SNR) and without averaging (Yuste and Katz, 1991; Grienberger and Konnerth, 2012)

  • Our results showed that QuasAr2 has the best performance among 8 genetically encoded voltage indicators (GEVIs) in vitro

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Summary

Graphical Abstract

Bando et al compare the performance of recently developed genetically encoded voltage indicators (GEVIs) under multiple experimental conditions in vitro and in vivo. Each indicator has advantages and disadvantages, and no single GEVI is ideal for every experiment. The results provide a guide for choosing optimal GEVIs for specific applications. Highlights d Side-by-side comparison of genetically encoded voltage indicators (GEVIs). D Side-by-side evaluation of 8 GEVIs in cultured neurons with 1-photon imaging d Side-by-side evaluation of 4 GEVIs in vivo with 1-photon and 2-photon imaging d Detection of optical field potential (OFP) with GEVIs in vivo. 2019, Cell Reports 26, 802–813 January 15, 2019 a 2018 The Author(s).

SUMMARY
INTRODUCTION
QuasAr2
RESULTS
H Archer1
H Stimulus-triggered average
DISCUSSION
G Stimulus-triggered average
METHOD DETAILS
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