Precision Calcium Imaging of Dense Neural Populations via a Cell-Body-Targeted Calcium Indicator

Or A. Shemesh; Changyang Linghu; Kiryl D. Piatkevich; Daniel Goodwin; Orhan Tunc Celiker; Howard J. Gritton; Michael F. Romano; Ruixuan Gao; Chih Chieh (Jay) Yu; Hua An Tseng; Seth Bensussen; Sujatha Narayan; Chao Tsung Yang; Limor Freifeld; Cody A. Siciliano; Ishan Gupta; Joyce Wang; Nikita Pak; Young Gyu Yoon; Jeremy F.P. Ullmann; Burcu Guner-Ataman; Habiba Noamany; Zoe R. Sheinkopf; Won Min Park; Shoh Asano; Amy E. Keating; James S. Trimmer; Jacob Reimer; Andreas S. Tolias; Mark F. Bear; Kay M. Tye; Xue Han; Misha B. Ahrens; Edward S. Boyden

doi:10.1016/j.neuron.2020.05.029

Precision Calcium Imaging of Dense Neural Populations via a Cell-Body-Targeted Calcium Indicator

Or A. Shemesh, Changyang Linghu, Kiryl D. Piatkevich, Daniel Goodwin, Orhan Tunc Celiker, Howard J. Gritton, Michael F. Romano, Ruixuan Gao, Chih Chieh (Jay) Yu, Hua An Tseng, Seth Bensussen, Sujatha Narayan, Chao Tsung Yang, Limor Freifeld, Cody A. Siciliano, Ishan Gupta, Joyce Wang, Nikita Pak, Young Gyu Yoon, Jeremy F.P. UllmannBurcu Guner-Ataman, Habiba Noamany, Zoe R. Sheinkopf, Won Min Park, Shoh Asano, Amy E. Keating, James S. Trimmer, Jacob Reimer, Andreas S. Tolias, Mark F. Bear, Kay M. Tye, Xue Han, Misha B. Ahrens, Edward S. Boyden^*

^*Corresponding author for this work

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

79 Scopus citations

Abstract

Methods for one-photon fluorescent imaging of calcium dynamics can capture the activity of hundreds of neurons across large fields of view at a low equipment complexity and cost. In contrast to two-photon methods, however, one-photon methods suffer from higher levels of crosstalk from neuropil, resulting in a decreased signal-to-noise ratio and artifactual correlations of neural activity. We address this problem by engineering cell-body-targeted variants of the fluorescent calcium indicators GCaMP6f and GCaMP7f. We screened fusions of GCaMP to natural, as well as artificial, peptides and identified fusions that localized GCaMP to within 50 μm of the cell body of neurons in mice and larval zebrafish. One-photon imaging of soma-targeted GCaMP in dense neural circuits reported fewer artifactual spikes from neuropil, an increased signal-to-noise ratio, and decreased artifactual correlation across neurons. Thus, soma-targeting of fluorescent calcium indicators facilitates usage of simple, powerful, one-photon methods for imaging neural calcium dynamics.

Original language	English
Pages (from-to)	470-486.e11
Journal	Neuron
Volume	107
Issue number	3
DOIs	https://doi.org/10.1016/j.neuron.2020.05.029
State	Published - 5 Aug 2020
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Inc.

Keywords

calcium imaging
correlation
crosstalk
GCaMP6
GCaMP7
in vivo imaging
microscopy
neuropil contamination
soma-targeting
two-photon microscopy

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10.1016/j.neuron.2020.05.029

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Shemesh, O. A., Linghu, C., Piatkevich, K. D., Goodwin, D., Celiker, O. T., Gritton, H. J., Romano, M. F., Gao, R., Yu, C. C., Tseng, H. A., Bensussen, S., Narayan, S., Yang, C. T., Freifeld, L., Siciliano, C. A., Gupta, I., Wang, J., Pak, N., Yoon, Y. G., ... Boyden, E. S. (2020). Precision Calcium Imaging of Dense Neural Populations via a Cell-Body-Targeted Calcium Indicator. Neuron, 107(3), 470-486.e11. https://doi.org/10.1016/j.neuron.2020.05.029

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title = "Precision Calcium Imaging of Dense Neural Populations via a Cell-Body-Targeted Calcium Indicator",

abstract = "Methods for one-photon fluorescent imaging of calcium dynamics can capture the activity of hundreds of neurons across large fields of view at a low equipment complexity and cost. In contrast to two-photon methods, however, one-photon methods suffer from higher levels of crosstalk from neuropil, resulting in a decreased signal-to-noise ratio and artifactual correlations of neural activity. We address this problem by engineering cell-body-targeted variants of the fluorescent calcium indicators GCaMP6f and GCaMP7f. We screened fusions of GCaMP to natural, as well as artificial, peptides and identified fusions that localized GCaMP to within 50 μm of the cell body of neurons in mice and larval zebrafish. One-photon imaging of soma-targeted GCaMP in dense neural circuits reported fewer artifactual spikes from neuropil, an increased signal-to-noise ratio, and decreased artifactual correlation across neurons. Thus, soma-targeting of fluorescent calcium indicators facilitates usage of simple, powerful, one-photon methods for imaging neural calcium dynamics.",

keywords = "calcium imaging, correlation, crosstalk, GCaMP6, GCaMP7, in vivo imaging, microscopy, neuropil contamination, soma-targeting, two-photon microscopy",

author = "Shemesh, {Or A.} and Changyang Linghu and Piatkevich, {Kiryl D.} and Daniel Goodwin and Celiker, {Orhan Tunc} and Gritton, {Howard J.} and Romano, {Michael F.} and Ruixuan Gao and Yu, {Chih Chieh (Jay)} and Tseng, {Hua An} and Seth Bensussen and Sujatha Narayan and Yang, {Chao Tsung} and Limor Freifeld and Siciliano, {Cody A.} and Ishan Gupta and Joyce Wang and Nikita Pak and Yoon, {Young Gyu} and Ullmann, {Jeremy F.P.} and Burcu Guner-Ataman and Habiba Noamany and Sheinkopf, {Zoe R.} and Park, {Won Min} and Shoh Asano and Keating, {Amy E.} and Trimmer, {James S.} and Jacob Reimer and Tolias, {Andreas S.} and Bear, {Mark F.} and Tye, {Kay M.} and Xue Han and Ahrens, {Misha B.} and Boyden, {Edward S.}",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = aug,

day = "5",

doi = "10.1016/j.neuron.2020.05.029",

language = "אנגלית",

volume = "107",

pages = "470--486.e11",

journal = "Neuron",

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Shemesh, OA, Linghu, C, Piatkevich, KD, Goodwin, D, Celiker, OT, Gritton, HJ, Romano, MF, Gao, R, Yu, CC, Tseng, HA, Bensussen, S, Narayan, S, Yang, CT, Freifeld, L, Siciliano, CA, Gupta, I, Wang, J, Pak, N, Yoon, YG, Ullmann, JFP, Guner-Ataman, B, Noamany, H, Sheinkopf, ZR, Park, WM, Asano, S, Keating, AE, Trimmer, JS, Reimer, J, Tolias, AS, Bear, MF, Tye, KM, Han, X, Ahrens, MB & Boyden, ES 2020, 'Precision Calcium Imaging of Dense Neural Populations via a Cell-Body-Targeted Calcium Indicator', Neuron, vol. 107, no. 3, pp. 470-486.e11. https://doi.org/10.1016/j.neuron.2020.05.029

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T1 - Precision Calcium Imaging of Dense Neural Populations via a Cell-Body-Targeted Calcium Indicator

AU - Shemesh, Or A.

AU - Linghu, Changyang

AU - Piatkevich, Kiryl D.

AU - Goodwin, Daniel

AU - Celiker, Orhan Tunc

AU - Gritton, Howard J.

AU - Romano, Michael F.

AU - Gao, Ruixuan

AU - Yu, Chih Chieh (Jay)

AU - Tseng, Hua An

AU - Bensussen, Seth

AU - Narayan, Sujatha

AU - Yang, Chao Tsung

AU - Freifeld, Limor

AU - Siciliano, Cody A.

AU - Gupta, Ishan

AU - Wang, Joyce

AU - Pak, Nikita

AU - Yoon, Young Gyu

AU - Ullmann, Jeremy F.P.

AU - Guner-Ataman, Burcu

AU - Noamany, Habiba

AU - Sheinkopf, Zoe R.

AU - Park, Won Min

AU - Asano, Shoh

AU - Keating, Amy E.

AU - Trimmer, James S.

AU - Reimer, Jacob

AU - Tolias, Andreas S.

AU - Bear, Mark F.

AU - Tye, Kay M.

AU - Han, Xue

AU - Ahrens, Misha B.

AU - Boyden, Edward S.

PY - 2020/8/5

Y1 - 2020/8/5

N2 - Methods for one-photon fluorescent imaging of calcium dynamics can capture the activity of hundreds of neurons across large fields of view at a low equipment complexity and cost. In contrast to two-photon methods, however, one-photon methods suffer from higher levels of crosstalk from neuropil, resulting in a decreased signal-to-noise ratio and artifactual correlations of neural activity. We address this problem by engineering cell-body-targeted variants of the fluorescent calcium indicators GCaMP6f and GCaMP7f. We screened fusions of GCaMP to natural, as well as artificial, peptides and identified fusions that localized GCaMP to within 50 μm of the cell body of neurons in mice and larval zebrafish. One-photon imaging of soma-targeted GCaMP in dense neural circuits reported fewer artifactual spikes from neuropil, an increased signal-to-noise ratio, and decreased artifactual correlation across neurons. Thus, soma-targeting of fluorescent calcium indicators facilitates usage of simple, powerful, one-photon methods for imaging neural calcium dynamics.

AB - Methods for one-photon fluorescent imaging of calcium dynamics can capture the activity of hundreds of neurons across large fields of view at a low equipment complexity and cost. In contrast to two-photon methods, however, one-photon methods suffer from higher levels of crosstalk from neuropil, resulting in a decreased signal-to-noise ratio and artifactual correlations of neural activity. We address this problem by engineering cell-body-targeted variants of the fluorescent calcium indicators GCaMP6f and GCaMP7f. We screened fusions of GCaMP to natural, as well as artificial, peptides and identified fusions that localized GCaMP to within 50 μm of the cell body of neurons in mice and larval zebrafish. One-photon imaging of soma-targeted GCaMP in dense neural circuits reported fewer artifactual spikes from neuropil, an increased signal-to-noise ratio, and decreased artifactual correlation across neurons. Thus, soma-targeting of fluorescent calcium indicators facilitates usage of simple, powerful, one-photon methods for imaging neural calcium dynamics.

KW - calcium imaging

KW - correlation

KW - crosstalk

KW - GCaMP6

KW - GCaMP7

KW - in vivo imaging

KW - microscopy

KW - neuropil contamination

KW - soma-targeting

KW - two-photon microscopy

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AN - SCOPUS:85087664780

SN - 0896-6273

VL - 107

SP - 470-486.e11

JO - Neuron

JF - Neuron

IS - 3

ER -

Precision Calcium Imaging of Dense Neural Populations via a Cell-Body-Targeted Calcium Indicator

Abstract

Bibliographical note

Keywords

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