Fast and sensitive GCaMP calcium indicators for imaging neural populations

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.

Automated summary

In this study, fast and sensitive GCaMP-type indicators were developed and optimized through large-scale screening and structure-guided mutagenesis. The resulting jGCaMP8' sensors, with ultra-fast kinetics and high sensitivity, can track large populations of neurons.