title: Neural circuits. Labeling of active neural circuits in vivo with designed calcium integrators.
abstract: 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.
authors: Howard Hughes Medical Institute, Janelia Farm Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA.
authors: Benjamin F
authors: BF
authors: Fosque
authors: Howard Hughes Medical Institute, Janelia Farm Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA.
authors: Yi
authors: Y
authors: Sun
authors: Howard Hughes Medical Institute, Janelia Farm Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA.
authors: Hod
authors: H
authors: Dana
authors: Howard Hughes Medical Institute, Janelia Farm Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA.
authors: Chao-Tsung
authors: CT
authors: Yang
authors: Howard Hughes Medical Institute, Janelia Farm Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA.
authors: Tomoko
authors: T
authors: Ohyama
authors: Howard Hughes Medical Institute, Janelia Farm Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA.
authors: Michael R
authors: MR
authors: Tadross
authors: Howard Hughes Medical Institute, Janelia Farm Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA.
authors: Ronak
authors: R
authors: Patel
authors: Howard Hughes Medical Institute, Janelia Farm Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA.
authors: Marta
authors: M
authors: Zlatic
authors: Howard Hughes Medical Institute, Janelia Farm Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA.
authors: Douglas S
authors: DS
authors: Kim
authors: Howard Hughes Medical Institute, Janelia Farm Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA.
authors: Misha B
authors: MB
authors: Ahrens
authors: Howard Hughes Medical Institute, Janelia Farm Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA.
authors: Vivek
authors: V
authors: Jayaraman
authors: Howard Hughes Medical Institute, Janelia Farm Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA.
authors: Loren L
authors: LL
authors: Looger
authors: Howard Hughes Medical Institute, Janelia Farm Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA. schreitere@janelia.hhmi.org.
authors: Eric R
authors: ER
authors: Schreiter
mesh_terms: D000818:Animals; D015374:Biosensing Techniques; D002118:Calcium / Q000032:analysis* / Q000378:metabolism; D004331:Drosophila melanogaster; D005453:Fluorescence; D017781:Genes, Immediate-Early; D007202:Indicators and Reagents / Q000032:analysis / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009434:Neural Pathways / Q000737:chemistry* / Q000166:cytology / Q000502:physiology; D051580:Neuronal Calcium-Sensor Proteins / Q000235:genetics / Q000378:metabolism*; D015202:Protein Engineering; D011984:Sensory Receptor Cells / Q000737:chemistry* / Q000502:physiology; D013194:Staining and Labeling / Q000379:methods*; D015027:Zebrafish
chemical_list: D007202:Indicators and Reagents; D008164:Luminescent Proteins; D051580:Neuronal Calcium-Sensor Proteins; D002118:Calcium