Fast and sensitive GCaMP calcium indicators for imaging neural populations

Yan Zhang, Márton Rózsa, Yajie Liang, Daniel Bushey, Ziqiang Wei, Jihong Zheng, Daniel Reep, Gerard Joey Broussard, Arthur Tsang, Getahun Tsegaye, Sujatha Narayan, Christopher J. Obara, Jing-Xuan Lim, Ronak Patel, Rongwei Zhang, Misha B. Ahrens, Glenn C. Turner (), Samuel S.-H. Wang (), Wyatt L. Korff, Eric R. Schreiter, Karel Svoboda (), Jeremy P. Hasseman (), Ilya Kolb and Loren L. Looger ()
Additional contact information
Yan Zhang: Howard Hughes Medical Institute
Márton Rózsa: Howard Hughes Medical Institute
Yajie Liang: Howard Hughes Medical Institute
Daniel Bushey: Howard Hughes Medical Institute
Ziqiang Wei: Howard Hughes Medical Institute
Jihong Zheng: Howard Hughes Medical Institute
Daniel Reep: Howard Hughes Medical Institute
Gerard Joey Broussard: Neuroscience Institute, Princeton University
Arthur Tsang: Howard Hughes Medical Institute
Getahun Tsegaye: Howard Hughes Medical Institute
Sujatha Narayan: Howard Hughes Medical Institute
Christopher J. Obara: Howard Hughes Medical Institute
Jing-Xuan Lim: Howard Hughes Medical Institute
Ronak Patel: Howard Hughes Medical Institute
Rongwei Zhang: Howard Hughes Medical Institute
Misha B. Ahrens: Howard Hughes Medical Institute
Glenn C. Turner: Howard Hughes Medical Institute
Samuel S.-H. Wang: Neuroscience Institute, Princeton University
Wyatt L. Korff: Howard Hughes Medical Institute
Eric R. Schreiter: Howard Hughes Medical Institute
Karel Svoboda: Howard Hughes Medical Institute
Jeremy P. Hasseman: Howard Hughes Medical Institute
Ilya Kolb: Howard Hughes Medical Institute
Loren L. Looger: Howard Hughes Medical Institute

Nature, 2023, vol. 615, issue 7954, 884-891

Abstract: 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 ‘jGCaMP8’ 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.

Date: 2023
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DOI: 10.1038/s41586-023-05828-9

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