Fast and sensitive GCaMP calcium indicators for imaging neural populations

Looger, L.; Zhang, Y.; Rozsa, M.; Liang, Y.; Bushey, D.; Wei, Z.; Zheng, J.; Reep, D.; Broussard, G. J.; Tsang, A.; Tsegaye, G.; Narayan, S.; Obara, C. J.; Lim, J.-X.; Patel, R.; Zhang, R.; Ahrens, M. B.; Turner, G. C.; Wang, S. S.; Korff, W.; Schreiter, E. R.; Svoboda, K.; Hasseman, J. P.; Kolb, I.

doi:10.1101/2021.11.08.467793

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bioRxiv · 10.1101/2021.11.08.467793

Fast and sensitive GCaMP calcium indicators for imaging neural populations

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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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Looger, L., Zhang, Y., Rozsa, M., Liang, Y., Bushey, D., Wei, Z., Zheng, J., Reep, D., Broussard, G. J., Tsang, A., Tsegaye, G., Narayan, S., Obara, C. J., Lim, J.-X., Patel, R., Zhang, R., Ahrens, M. B., Turner, G. C., Wang, S. S., Korff, W., Schreiter, E. R., Svoboda, K., Hasseman, J. P., Kolb, I.. 2021-11-08. Fast and sensitive GCaMP calcium indicators for imaging neural populations. https://doi.org/10.1101/2021.11.08.467793

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