@article{11bac35620e54304a92a9c41c93d7c37,
title = "Fast and sensitive GCaMP calcium indicators for imaging neural populations",
abstract = "Calcium imaging with protein-based indicators1,2 is widely used to follow neural activity in intact nervous systems, but current protein sensors report neural activity at timescales much slower than electrical signalling and are limited by trade-offs between sensitivity and kinetics. Here we used large-scale screening and structure-guided mutagenesis to develop and optimize several fast and sensitive GCaMP-type indicators3–8. The resulting {\textquoteleft}jGCaMP8{\textquoteright} sensors, based on the calcium-binding protein calmodulin and a fragment of endothelial nitric oxide synthase, have ultra-fast kinetics (half-rise times of 2 ms) and the highest sensitivity for neural activity reported for a protein-based calcium sensor. jGCaMP8 sensors will allow tracking of large populations of neurons on timescales relevant to neural computation.",
author = "Yan Zhang and M{\'a}rton R{\'o}zsa and Yajie Liang and Daniel Bushey and Ziqiang Wei and Jihong Zheng and Daniel Reep and Broussard, {Gerard Joey} and Arthur Tsang and Getahun Tsegaye and Sujatha Narayan and Obara, {Christopher J.} and Lim, {Jing Xuan} and Ronak Patel and Rongwei Zhang and Ahrens, {Misha B.} and Turner, {Glenn C.} and Wang, {Samuel S.H.} and Korff, {Wyatt L.} and Schreiter, {Eric R.} and Karel Svoboda and Hasseman, {Jeremy P.} and Ilya Kolb and Looger, {Loren L.}",
note = "Funding Information: This work was done as a collaboration with the Janelia Genetically Encoded Indicator and Effector Project Team (GENIE; https://www.janelia.org/project-team/genie) at the Howard Hughes Medical Institute, Janelia Research Campus. J.Z., D.R., A.T., G.T., J.P.H. and I.K. are members of GENIE. G.C.T., W.L.K., E.R.S., K.S., J.P.H., I.K. and L.L.L. are on the GENIE Steering Committee. We thank additional GENIE Steering Committee members V. Jayaraman, N. Spruston and A. Tebo for useful discussions. The work was supported by the Howard Hughes Medical Institute, NIH U19 NS104648 and NIH R01 NS045193 to S.S.-H.W., and NIH F32 MH120887 to G.J.B. We thank the Berkeley Center for Structural Biology for use of beamline 8.2.1; and are grateful to the Viral Tools, Cell and Tissue Culture, Molecular Biology, Media Prep, Vivarium/Aquarium, Anatomy and Histology, and Fly Facility Shared Resources at Janelia for technical assistance with numerous parts of the project. Funding Information: This work was done as a collaboration with the Janelia Genetically Encoded Indicator and Effector Project Team (GENIE; https://www.janelia.org/project-team/genie ) at the Howard Hughes Medical Institute, Janelia Research Campus. J.Z., D.R., A.T., G.T., J.P.H. and I.K. are members of GENIE. G.C.T., W.L.K., E.R.S., K.S., J.P.H., I.K. and L.L.L. are on the GENIE Steering Committee. We thank additional GENIE Steering Committee members V. Jayaraman, N. Spruston and A. Tebo for useful discussions. The work was supported by the Howard Hughes Medical Institute, NIH U19 NS104648 and NIH R01 NS045193 to S.S.-H.W., and NIH F32 MH120887 to G.J.B. We thank the Berkeley Center for Structural Biology for use of beamline 8.2.1; and are grateful to the Viral Tools, Cell and Tissue Culture, Molecular Biology, Media Prep, Vivarium/Aquarium, Anatomy and Histology, and Fly Facility Shared Resources at Janelia for technical assistance with numerous parts of the project. Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
month = mar,
day = "30",
doi = "10.1038/s41586-023-05828-9",
language = "English (US)",
volume = "615",
pages = "884--891",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7954",
}