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Bright and fast multicoloured voltage reporters via electrochromic FRET

Author

Listed:
  • Peng Zou

    (Harvard Stem Cell Institute, Harvard University)

  • Yongxin Zhao

    (University of Alberta)

  • Adam D. Douglass

    (University of Utah)

  • Daniel R. Hochbaum

    (Harvard Stem Cell Institute, Harvard University)

  • Daan Brinks

    (Harvard Stem Cell Institute, Harvard University)

  • Christopher A. Werley

    (Harvard Stem Cell Institute, Harvard University)

  • D. Jed Harrison

    (University of Alberta)

  • Robert E. Campbell

    (University of Alberta)

  • Adam E. Cohen

    (Harvard Stem Cell Institute, Harvard University
    Howard Hughes Medical Institute, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA)

Abstract

Genetically encoded fluorescent reporters of membrane potential promise to reveal aspects of neural function not detectable by other means. We present a palette of multicoloured brightly fluorescent genetically encoded voltage indicators with sensitivities from 8–13% ΔF/F per 100 mV, and half-maximal response times from 4–7 ms. A fluorescent protein is fused to an archaerhodopsin-derived voltage sensor. Voltage-induced shifts in the absorption spectrum of the rhodopsin lead to voltage-dependent nonradiative quenching of the appended fluorescent protein. Through a library screen, we identify linkers and fluorescent protein combinations that report neuronal action potentials in cultured rat hippocampal neurons with a single-trial signal-to-noise ratio from 7 to 9 in a 1 kHz imaging bandwidth at modest illumination intensity. The freedom to choose a voltage indicator from an array of colours facilitates multicolour voltage imaging, as well as combination with other optical reporters and optogenetic actuators.

Suggested Citation

  • Peng Zou & Yongxin Zhao & Adam D. Douglass & Daniel R. Hochbaum & Daan Brinks & Christopher A. Werley & D. Jed Harrison & Robert E. Campbell & Adam E. Cohen, 2014. "Bright and fast multicoloured voltage reporters via electrochromic FRET," Nature Communications, Nature, vol. 5(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5625
    DOI: 10.1038/ncomms5625
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    Cited by:

    1. Amelie C. F. Bergs & Jana F. Liewald & Silvia Rodriguez-Rozada & Qiang Liu & Christin Wirt & Artur Bessel & Nadja Zeitzschel & Hilal Durmaz & Adrianna Nozownik & Holger Dill & Maëlle Jospin & Johannes, 2023. "All-optical closed-loop voltage clamp for precise control of muscles and neurons in live animals," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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