Fluorescence Imaging of Neural Activity, Neurochemical Dynamics, and Drug-Specific Receptor Conformation with Genetically Encoded Sensors

Annu Rev Neurosci. 2022 Jul 8;45:273-294. doi: 10.1146/annurev-neuro-110520-031137. Epub 2022 Mar 22.


Recent advances in fluorescence imaging permit large-scale recording of neural activity and dynamics of neurochemical release with unprecedented resolution in behaving animals. Calcium imaging with highly optimized genetically encoded indicators provides a mesoscopic view of neural activity from genetically defined populations at cellular and subcellular resolutions. Rigorously improved voltage sensors and microscopy allow for robust spike imaging of populational neurons in various brain regions. In addition, recent protein engineering efforts in the past few years have led to the development of sensors for neurotransmitters and neuromodulators. Here, we discuss the development and applications of these genetically encoded fluorescent indicators in reporting neural activity in response to various behaviors in different biological systems as well as in drug discovery. We also report a simple model to guide sensor selection and optimization.

Keywords: biosensors; drug discovery; fluorescence imaging; genetically encoded indicators; neurocircuit imaging; neuromodulation.

Publication types

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

MeSH terms

  • Animals
  • Brain / metabolism
  • Neurons* / physiology
  • Neurotransmitter Agents / metabolism
  • Optical Imaging
  • Receptors, Drug* / metabolism


  • Neurotransmitter Agents
  • Receptors, Drug