Fast and sensitive GCaMP calcium indicators for imaging neural populations

By Yan Zhang, Márton Rózsa, Yajie Liang, Daniel Bushey, Ziqiang Wei, Jihong Zheng, Daniel Reep, G. Broussard, Arthur Tsang, G. Tsegaye and 14 more. bioRxiv, 2021

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Using large-scale screening and structure-guided mutagenesis, fast and sensitive GCaMP sensors are developed and optimized with improved kinetics without compromising sensitivity or brightness. 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.

Subfields: Biophysics, Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3b9347aaaeb0b92a24e094930801424c36c68732