PT - JOURNAL ARTICLE AU - Yan Zhang AU - Márton Rózsa AU - Yajie Liang AU - Daniel Bushey AU - Ziqiang Wei AU - Jihong Zheng AU - Daniel Reep AU - Gerard Joey Broussard AU - Arthur Tsang AU - Getahun Tsegaye AU - Sujatha Narayan AU - Christopher J. Obara AU - Jing-Xuan Lim AU - Ronak Patel AU - Rongwei Zhang AU - Misha B. Ahrens AU - Glenn C. Turner AU - Samuel S.-H. Wang AU - Wyatt L. Korff AU - Eric R. Schreiter AU - Karel Svoboda AU - Jeremy P. Hasseman AU - Ilya Kolb AU - Loren L. Looger TI - Fast and sensitive GCaMP calcium indicators for imaging neural populations AID - 10.1101/2021.11.08.467793 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.11.08.467793 4099 - http://biorxiv.org/content/early/2021/11/10/2021.11.08.467793.short 4100 - http://biorxiv.org/content/early/2021/11/10/2021.11.08.467793.full AB - Calcium imaging with protein-based indicators is widely used to follow neural activity in intact nervous systems. The popular GCaMP indicators are based on the calcium-binding protein calmodulin and the RS20 peptide. These sensors report neural activity at timescales much slower than electrical signaling, limited by their biophysical properties and trade-offs between sensitivity and speed. We used large-scale screening and structure-guided mutagenesis to develop and optimize several fast and sensitive GCaMP-type indicators. The resulting ‘jGCaMP8’ sensors, based on calmodulin and a fragment of endothelial nitric oxide synthase, have ultra-fast kinetics (rise times, 2 ms) and still feature the highest sensitivity for neural activity reported for any protein-based sensor. jGCaMP8 sensors will allow tracking of larger populations of neurons on timescales relevant to neural computation.Competing Interest StatementYZ, ERS, JPH, IK, and LLL are inventors of US Patent Application 63082222, Genetically Encoded Calcium Indicators and Methods of Use, which covers the jGCaMP8 sensors.