Neural circuits. Labeling of active neural circuits in vivo with designed calcium integrators.


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.

DOI: 10.1126/science.1260922

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@article{Fosque2015NeuralCL, title={Neural circuits. Labeling of active neural circuits in vivo with designed calcium integrators.}, author={Benjamin F. Fosque and Yi Ki Sun and Hod Dana and Chao-Tsung Yang and Tomoko Ohyama and Michael R Tadross and Ronak N. Patel and Marta Zlatic and Douglas S Kim and Misha B Ahrens and Vivek Jayaraman and Loren L. Looger and Eric R. Schreiter}, journal={Science}, year={2015}, volume={347 6223}, pages={755-60} }