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 John Obara; Jing-Xuan Lim; Ronak H. 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; Loren L. Looger

doi:10.1038/s41586-023-05828-9

NeuroscienceNatureMar 15, 2023

Peer-reviewed journal article

Fast and sensitive GCaMP calcium indicators for imaging neural populations

Yan Zhang iD, Márton Rózsa iD, Yajie Liang iD, Daniel Bushey iD, Ziqiang Wei iD, Jihong Zheng iD, Daniel Reep iD, Gerard Joey Broussard iD, Arthur Tsang iD, Getahun Tsegaye, Sujatha Narayan iD, Christopher John Obara iD, Jing-Xuan Lim iD, Ronak H. Patel iD, Rongwei Zhang iD, Misha B. Ahrens iD, Glenn C Turner iD, Samuel S.‐H. Wang iD, Wyatt L. Korff iD, Eric R. Schreiter iD, Karel Svoboda iD, Jeremy P. Hasseman iD, Ilya Kolb iD, Loren L. Looger iD

Abstract

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.

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