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 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

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 C. Turner, Samuel S.H. Wang, Wyatt L. Korff, Eric R. SchreiterKarel Svoboda, Jeremy P. Hasseman, Ilya Kolb, Loren L. Looger

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193 Scopus citations

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.

Original language	English (US)
Pages (from-to)	884-891
Number of pages	8
Journal	Nature
Volume	615
Issue number	7954
DOIs	https://doi.org/10.1038/s41586-023-05828-9
State	Published - Mar 30 2023

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Zhang, Y., Rózsa, 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. H., Korff, W. L., ... Looger, L. L. (2023). Fast and sensitive GCaMP calcium indicators for imaging neural populations. Nature, 615(7954), 884-891. https://doi.org/10.1038/s41586-023-05828-9

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title = "Fast and sensitive GCaMP calcium indicators for imaging neural populations",

abstract = "Calcium imaging with protein-based indicators1,2 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 indicators3–8. The resulting {\textquoteleft}jGCaMP8{\textquoteright} 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.",

author = "Yan Zhang and M{\'a}rton R{\'o}zsa and Yajie Liang and Daniel Bushey and Ziqiang Wei and Jihong Zheng and Daniel Reep and Broussard, {Gerard Joey} and Arthur Tsang and Getahun Tsegaye and Sujatha Narayan and Obara, {Christopher J.} and Lim, {Jing Xuan} and Ronak Patel and Rongwei Zhang and Ahrens, {Misha B.} and Turner, {Glenn C.} and Wang, {Samuel S.H.} and Korff, {Wyatt L.} and Schreiter, {Eric R.} and Karel Svoboda and Hasseman, {Jeremy P.} and Ilya Kolb and Looger, {Loren L.}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = mar,

day = "30",

doi = "10.1038/s41586-023-05828-9",

language = "English (US)",

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Zhang, Y, Rózsa, M, Liang, Y, Bushey, D, Wei, Z, Zheng, J, Reep, D, Broussard, GJ, Tsang, A, Tsegaye, G, Narayan, S, Obara, CJ, Lim, JX, Patel, R, Zhang, R, Ahrens, MB, Turner, GC, Wang, SSH, Korff, WL, Schreiter, ER, Svoboda, K, Hasseman, JP, Kolb, I & Looger, LL 2023, 'Fast and sensitive GCaMP calcium indicators for imaging neural populations', Nature, vol. 615, no. 7954, pp. 884-891. https://doi.org/10.1038/s41586-023-05828-9

TY - JOUR

T1 - Fast and sensitive GCaMP calcium indicators for imaging neural populations

AU - Zhang, Yan

AU - Rózsa, Márton

AU - Liang, Yajie

AU - Bushey, Daniel

AU - Wei, Ziqiang

AU - Zheng, Jihong

AU - Reep, Daniel

AU - Broussard, Gerard Joey

AU - Tsang, Arthur

AU - Tsegaye, Getahun

AU - Narayan, Sujatha

AU - Obara, Christopher J.

AU - Lim, Jing Xuan

AU - Patel, Ronak

AU - Zhang, Rongwei

AU - Ahrens, Misha B.

AU - Turner, Glenn C.

AU - Wang, Samuel S.H.

AU - Korff, Wyatt L.

AU - Schreiter, Eric R.

AU - Svoboda, Karel

AU - Hasseman, Jeremy P.

AU - Kolb, Ilya

AU - Looger, Loren L.

PY - 2023/3/30

Y1 - 2023/3/30

N2 - Calcium imaging with protein-based indicators1,2 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 indicators3–8. 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.

AB - Calcium imaging with protein-based indicators1,2 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 indicators3–8. 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.

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SP - 884

EP - 891

JO - Nature

JF - Nature

IS - 7954

ER -

Fast and sensitive GCaMP calcium indicators for imaging neural populations

Abstract

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