4.8 Article

Comparative Evaluation of Genetically Encoded Voltage Indicators

Journal

CELL REPORTS
Volume 26, Issue 3, Pages 802-+

Publisher

CELL PRESS
DOI: 10.1016/j.celrep.2018.12.088

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Funding

  1. NEI [DP1EY024503, R01EY011787]
  2. National Institute of Mental Health (NIMH) [R01MH101218, R01MH100561]
  3. US Army Research Laboratory
  4. US Army Research Office (ARO) [W911NF-12-1-0594]
  5. Uehara Memorial Foundation
  6. Japan Society for the Promotion of Science (JSPS)
  7. program for Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) from the Japan Agency for Medical Research and Development (AMED) [JP18dm0207059]
  8. Summer Undergraduate Research Fellowship
  9. Columbia's Class of 1939 Summer Research Fellowship
  10. Marie Curie Fellowship

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Imaging 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.

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