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Fast and sensitive GCaMP calcium indicators for imaging neural populations

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

in 14/35 / 14/63 / 631/1647/1888/2249 / 631/378/3920 / 64/24 / 64/60 / 82/47 / 9/10 / Calcium / Calcium - analysis / Calcium - metabolism / Calcium imaging / Calcium Signaling / Calcium-binding protein / Calmodulin / Calmodulin - metabolism / Graphs / Humanities and Social Sciences / Kinases / Kinetics / multidisciplinary / Mutagenesis / Neurons - metabolism / Nitric oxide / Nitric Oxide Synthase Type III - chemistry / Nitric Oxide Synthase Type III - metabolism / Nitric-oxide synthase / Peptide Fragments - chemistry / Peptide Fragments - metabolism / Populations / Proteins / Science / Science (multidisciplinary) / Sensitivity / Sensors / Time Factors

2023

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2023

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2023

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Journal Article

Fast and sensitive GCaMP calcium indicators for imaging neural populations

Zhang, Rongwei,

Tsegaye, Getahun,

Ahrens, Misha B.,

Looger, Loren L.,

Zheng, Jihong,

Wang, Samuel S.-H.,

Bushey, Daniel,

Rózsa, Márton,

Schreiter, Eric R.,

Reep, Daniel,

Patel, Ronak,

Liang, Yajie,

Wei, Ziqiang,

Obara, Christopher J.,

Korff, Wyatt L.,

Kolb, Ilya,

Lim, Jing-Xuan,

Hasseman, Jeremy P.,

Turner, Glenn C.,

Narayan, Sujatha,

Svoboda, Karel,

Zhang, Yan,

Tsang, Arthur,

Broussard, Gerard Joey

2023

Overview

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. 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.

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Publisher

Nature Publishing Group UK,Nature Publishing Group

Subject

14/35

/ 14/63

/ 631/1647/1888/2249

/ 631/378/3920

/ 64/24

/ 64/60

/ 82/47