Designs and sensing mechanisms of genetically encoded fluorescent voltage indicators

Curr Opin Chem Biol. 2015 Aug;27:31-8. doi: 10.1016/j.cbpa.2015.05.003. Epub 2015 Jun 12.


Neurons tightly regulate the electrical potential difference across the plasma membrane with millivolt accuracy and millisecond resolution. Membrane voltage dynamics underlie the generation of an impulse, the transduction of impulses from one end of the neuron to the other, and the release of neurotransmitters. Imaging these voltage dynamics in multiple neurons simultaneously is therefore crucial for understanding how neurons function together within circuits in intact brains. Genetically encoded fluorescent voltage sensors have long been desired to report voltage in defined subsets of neurons with optical readout. In this review, we discuss the diverse strategies used to design and optimize protein-based voltage sensors, and highlight the chemical mechanisms by which different classes of reporters sense voltage. To guide neuroscientists in choosing an appropriate sensor for their applications, we also describe operating trade-offs of each class of voltage indicators.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Biosensing Techniques / instrumentation
  • Biosensing Techniques / methods*
  • Cell Membrane / metabolism
  • Cell Membrane / physiology
  • Fluorescent Dyes / chemistry*
  • Humans
  • Luminescent Proteins / chemistry*
  • Neurons / metabolism
  • Neurons / physiology
  • Protein Binding
  • Voltage-Sensitive Dye Imaging / instrumentation
  • Voltage-Sensitive Dye Imaging / methods*


  • Fluorescent Dyes
  • Luminescent Proteins