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 Turner, Samuel S.‐H. Wang, Wyatt Korff, Eric R. Schreiter, Karel Svoboda, J. Hasseman, Ilya Kolb, Loren L. Looger
Abstract
Abstract Calcium imaging with protein-based indicators 1,2 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 indicators 3–8 . 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.