High-fidelity optical reporting of neuronal electrical activity with an ultrafast fluorescent voltage sensor

Nat Neurosci. 2014 Jun;17(6):884-9. doi: 10.1038/nn.3709. Epub 2014 Apr 22.


Accurate optical reporting of electrical activity in genetically defined neuronal populations is a long-standing goal in neuroscience. We developed Accelerated Sensor of Action Potentials 1 (ASAP1), a voltage sensor design in which a circularly permuted green fluorescent protein is inserted in an extracellular loop of a voltage-sensing domain, rendering fluorescence responsive to membrane potential. ASAP1 demonstrated on and off kinetics of ∼ 2 ms, reliably detected single action potentials and subthreshold potential changes, and tracked trains of action potential waveforms up to 200 Hz in single trials. With a favorable combination of brightness, dynamic range and speed, ASAP1 enables continuous monitoring of membrane potential in neurons at kilohertz frame rates using standard epifluorescence microscopy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Cells, Cultured
  • Chickens
  • Ciona intestinalis
  • Female
  • Fluorescent Dyes*
  • HEK293 Cells
  • Humans
  • Mice
  • Molecular Sequence Data
  • Neurons / chemistry
  • Neurons / physiology*
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Voltage-Sensitive Dye Imaging / methods*
  • Xenopus laevis
  • Zebrafish


  • Fluorescent Dyes

Associated data

  • GENBANK/KJ598785