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. (2015). Neural circuits. Labeling of active neural circuits in vivo with designed calcium integrators.  Science 347(6223): 755--760.

FBrf0227755

Research paper

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.