High-performance calcium sensors for imaging activity in neuronal populations and microcompartments

Hod Dana; Yi Sun; Boaz Mohar; Brad K. Hulse; Aaron M. Kerlin; Jeremy P. Hasseman; Getahun Tsegaye; Arthur Tsang; Allan Wong; Ronak Patel; John J. Macklin; Yang Chen; Arthur Konnerth; Vivek Jayaraman; Loren L. Looger; Eric R. Schreiter; Karel Svoboda; Douglas S. Kim

doi:10.1038/s41592-019-0435-6

High-performance calcium sensors for imaging activity in neuronal populations and microcompartments

Hod Dana, Yi Sun, Boaz Mohar, Brad K. Hulse, Aaron M. Kerlin, Jeremy P. Hasseman, Getahun Tsegaye, Arthur Tsang, Allan Wong, Ronak Patel, John J. Macklin, Yang Chen, Arthur Konnerth, Vivek Jayaraman, Loren L. Looger, Eric R. Schreiter, Karel Svoboda, Douglas S. Kim

Neuroscience

Research output: Contribution to journal › Article › peer-review

568 Scopus citations

Abstract

Calcium imaging with genetically encoded calcium indicators (GECIs) is routinely used to measure neural activity in intact nervous systems. GECIs are frequently used in one of two different modes: to track activity in large populations of neuronal cell bodies, or to follow dynamics in subcellular compartments such as axons, dendrites and individual synaptic compartments. Despite major advances, calcium imaging is still limited by the biophysical properties of existing GECIs, including affinity, signal-to-noise ratio, rise and decay kinetics and dynamic range. Using structure-guided mutagenesis and neuron-based screening, we optimized the green fluorescent protein-based GECI GCaMP6 for different modes of in vivo imaging. The resulting jGCaMP7 sensors provide improved detection of individual spikes (jGCaMP7s,f), imaging in neurites and neuropil (jGCaMP7b), and may allow tracking larger populations of neurons using two-photon (jGCaMP7s,f) or wide-field (jGCaMP7c) imaging.

Original language	English (US)
Pages (from-to)	649-657
Number of pages	9
Journal	Nature Methods
Volume	16
Issue number	7
DOIs	https://doi.org/10.1038/s41592-019-0435-6
State	Published - Jul 1 2019

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© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.

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Dana, H., Sun, Y., Mohar, B., Hulse, B. K., Kerlin, A. M., Hasseman, J. P., Tsegaye, G., Tsang, A., Wong, A., Patel, R., Macklin, J. J., Chen, Y., Konnerth, A., Jayaraman, V., Looger, L. L., Schreiter, E. R., Svoboda, K., & Kim, D. S. (2019). High-performance calcium sensors for imaging activity in neuronal populations and microcompartments. Nature Methods, 16(7), 649-657. https://doi.org/10.1038/s41592-019-0435-6

Dana, H, Sun, Y, Mohar, B, Hulse, BK, Kerlin, AM, Hasseman, JP, Tsegaye, G, Tsang, A, Wong, A, Patel, R, Macklin, JJ, Chen, Y, Konnerth, A, Jayaraman, V, Looger, LL, Schreiter, ER, Svoboda, K & Kim, DS 2019, 'High-performance calcium sensors for imaging activity in neuronal populations and microcompartments', Nature Methods, vol. 16, no. 7, pp. 649-657. https://doi.org/10.1038/s41592-019-0435-6

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AU - Kim, Douglas S.

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High-performance calcium sensors for imaging activity in neuronal populations and microcompartments

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