ZFIN ID: ZDB-PUB-150214-7
Labeling of active neural circuits in vivo with designed calcium integrators
Fosque, B.F., Sun, Y., Dana, H., Yang, C.T., Ohyama, T., Tadross, M.R., Patel, R., Zlatic, M., Kim, D.S., Ahrens, M.B., Jayaraman, V., Looger, L.L., Schreiter, E.R.
Date: 2015
Source: Science (New York, N.Y.)   347: 755-760 (Journal)
Registered Authors: Ahrens, Misha, Sun, Yi, Yang, Chao-Tsung
Keywords: none
MeSH Terms:
  • Animals
  • Biosensing Techniques*
  • Calcium/analysis*
  • Calcium/metabolism
  • Drosophila melanogaster
  • Fluorescence
  • Genes, Immediate-Early*
  • Indicators and Reagents/analysis
  • Indicators and Reagents/metabolism
  • Luminescent Proteins/genetics
  • Luminescent Proteins/metabolism*
  • Mice
  • Neural Pathways/chemistry*
  • Neural Pathways/cytology
  • Neural Pathways/physiology
  • Neuronal Calcium-Sensor Proteins/genetics
  • Neuronal Calcium-Sensor Proteins/metabolism*
  • Protein Engineering
  • Sensory Receptor Cells/chemistry*
  • Sensory Receptor Cells/physiology
  • Staining and Labeling/methods*
  • Zebrafish
PubMed: 25678659 Full text @ Science
The identification of active neurons and circuits in vivo is a fundamental challenge in understanding the neural basis of behavior. Genetically encoded calcium (Ca(2+)) indicators (GECIs) enable quantitative monitoring of cellular-resolution activity during behavior. However, such indicators require online monitoring within a limited field of view. Alternatively, post hoc staining of immediate early genes (IEGs) indicates highly active cells within the entire brain, albeit with poor temporal resolution. We designed a fluorescent sensor, CaMPARI, that combines the genetic targetability and quantitative link to neural activity of GECIs with the permanent, large-scale labeling of IEGs, allowing a temporally precise "activity snapshot" of a large tissue volume. CaMPARI undergoes efficient and irreversible green-to-red conversion only when elevated intracellular Ca(2+) and experimenter-controlled illumination coincide. We demonstrate the utility of CaMPARI in freely moving larvae of zebrafish and flies, and in head-fixed mice and adult flies.