High-fidelity estimates of spikes and subthreshold waveforms from 1-photon voltage imaging in vivo

Michael E. Xie; Yoav Adam; Linlin Z. Fan; Urs L. Böhm; Ian Kinsella; Ding Zhou; Marton Rozsa; Amrita Singh; Karel Svoboda; Liam Paninski; Adam E. Cohen

doi:10.1016/j.celrep.2021.108954

High-fidelity estimates of spikes and subthreshold waveforms from 1-photon voltage imaging in vivo

Michael E. Xie, Yoav Adam, Linlin Z. Fan, Urs L. Böhm, Ian Kinsella, Ding Zhou, Marton Rozsa, Amrita Singh, Karel Svoboda, Liam Paninski^*, Adam E. Cohen^*

^*Corresponding author for this work

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

13 Scopus citations

Abstract

The ability to probe the membrane potential of multiple genetically defined neurons simultaneously would have a profound impact on neuroscience research. Genetically encoded voltage indicators are a promising tool for this purpose, and recent developments have achieved a high signal-to-noise ratio in vivo with 1-photon fluorescence imaging. However, these recordings exhibit several sources of noise and signal extraction remains a challenge. We present an improved signal extraction pipeline, spike-guided penalized matrix decomposition-nonnegative matrix factorization (SGPMD-NMF), which resolves supra- and subthreshold voltages in vivo. The method incorporates biophysical and optical constraints. We validate the pipeline with simultaneous patch-clamp and optical recordings from mouse layer 1 in vivo and with simulated and composite datasets with realistic noise. We demonstrate applications to mouse hippocampus expressing paQuasAr3-s or SomArchon1, mouse cortex expressing SomArchon1 or Voltron, and zebrafish spines expressing zArchon1.

Original language	American English
Article number	108954
Journal	Cell Reports
Volume	35
Issue number	1
DOIs	https://doi.org/10.1016/j.celrep.2021.108954
State	Published - 6 Apr 2021
Externally published	Yes

Bibliographical note

Funding Information:
M.E.X., Y.A., L.Z.F., U.L.B., and A.E.C. were supported by the Harvard Data Science Initiative , NIH grant R01MH117042 , and the Howard Hughes Medical Institute . I.K., D.Z., and L.P. were supported by NIH grant R01EB22913 . A.S., M.R., and K.S. were supported by the Howard Hughes Medical Institute . We thank C. Cai and A. Giovannuci for helpful discussions. We thank T. Kawashima, M. Ahrens, E. Jung, K. Piatkevich, and E. Boyden for zArchon1 zebrafish transgenics. The computations in this paper were run on the FASRC Cannon cluster supported by the FAS Division of the Science Research Computing Group at Harvard University.

Funding Information:
M.E.X. Y.A. L.Z.F. U.L.B. and A.E.C. were supported by the Harvard Data Science Initiative, NIH grant R01MH117042, and the Howard Hughes Medical Institute. I.K. D.Z. and L.P. were supported by NIH grant R01EB22913. A.S. M.R. and K.S. were supported by the Howard Hughes Medical Institute. We thank C. Cai and A. Giovannuci for helpful discussions. We thank T. Kawashima, M. Ahrens, E. Jung, K. Piatkevich, and E. Boyden for zArchon1 zebrafish transgenics. The computations in this paper were run on the FASRC Cannon cluster supported by the FAS Division of the Science Research Computing Group at Harvard University. M.E.X. wrote the code and analyzed the data. Y.A. acquired paQuasAr3-s and SomArchon1 data in hippocampus. L.Z.F. acquired SomArchon1 data in L1. U.L.B. acquired zArchon1 data in zebrafish spinal cord. I.K. D.Z. and L.P. contributed to the SGPMD-NMF algorithm. M.R. and A.S. acquired simultaneous patch-clamp and Voltron recordings in cortical L1. K.S. L.P. and A.E.C. supervised the research. M.E.X. L.P. and A.E.C. wrote the manuscript with input from all authors. A.E.C. is a co-founder of Q-State Biosciences. The other authors declare no competing interests.

Publisher Copyright:
© 2021 The Author(s)

Keywords

signal extraction
voltage imaging

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10.1016/j.celrep.2021.108954

Cite this

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title = "High-fidelity estimates of spikes and subthreshold waveforms from 1-photon voltage imaging in vivo",

abstract = "The ability to probe the membrane potential of multiple genetically defined neurons simultaneously would have a profound impact on neuroscience research. Genetically encoded voltage indicators are a promising tool for this purpose, and recent developments have achieved a high signal-to-noise ratio in vivo with 1-photon fluorescence imaging. However, these recordings exhibit several sources of noise and signal extraction remains a challenge. We present an improved signal extraction pipeline, spike-guided penalized matrix decomposition-nonnegative matrix factorization (SGPMD-NMF), which resolves supra- and subthreshold voltages in vivo. The method incorporates biophysical and optical constraints. We validate the pipeline with simultaneous patch-clamp and optical recordings from mouse layer 1 in vivo and with simulated and composite datasets with realistic noise. We demonstrate applications to mouse hippocampus expressing paQuasAr3-s or SomArchon1, mouse cortex expressing SomArchon1 or Voltron, and zebrafish spines expressing zArchon1.",

keywords = "signal extraction, voltage imaging",

author = "Xie, {Michael E.} and Yoav Adam and Fan, {Linlin Z.} and B{\"o}hm, {Urs L.} and Ian Kinsella and Ding Zhou and Marton Rozsa and Amrita Singh and Karel Svoboda and Liam Paninski and Cohen, {Adam E.}",

note = "Funding Information: M.E.X., Y.A., L.Z.F., U.L.B., and A.E.C. were supported by the Harvard Data Science Initiative , NIH grant R01MH117042 , and the Howard Hughes Medical Institute . I.K., D.Z., and L.P. were supported by NIH grant R01EB22913 . A.S., M.R., and K.S. were supported by the Howard Hughes Medical Institute . We thank C. Cai and A. Giovannuci for helpful discussions. We thank T. Kawashima, M. Ahrens, E. Jung, K. Piatkevich, and E. Boyden for zArchon1 zebrafish transgenics. The computations in this paper were run on the FASRC Cannon cluster supported by the FAS Division of the Science Research Computing Group at Harvard University. Funding Information: M.E.X. Y.A. L.Z.F. U.L.B. and A.E.C. were supported by the Harvard Data Science Initiative, NIH grant R01MH117042, and the Howard Hughes Medical Institute. I.K. D.Z. and L.P. were supported by NIH grant R01EB22913. A.S. M.R. and K.S. were supported by the Howard Hughes Medical Institute. We thank C. Cai and A. Giovannuci for helpful discussions. We thank T. Kawashima, M. Ahrens, E. Jung, K. Piatkevich, and E. Boyden for zArchon1 zebrafish transgenics. The computations in this paper were run on the FASRC Cannon cluster supported by the FAS Division of the Science Research Computing Group at Harvard University. M.E.X. wrote the code and analyzed the data. Y.A. acquired paQuasAr3-s and SomArchon1 data in hippocampus. L.Z.F. acquired SomArchon1 data in L1. U.L.B. acquired zArchon1 data in zebrafish spinal cord. I.K. D.Z. and L.P. contributed to the SGPMD-NMF algorithm. M.R. and A.S. acquired simultaneous patch-clamp and Voltron recordings in cortical L1. K.S. L.P. and A.E.C. supervised the research. M.E.X. L.P. and A.E.C. wrote the manuscript with input from all authors. A.E.C. is a co-founder of Q-State Biosciences. The other authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 The Author(s)",

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AU - Xie, Michael E.

AU - Adam, Yoav

AU - Fan, Linlin Z.

AU - Böhm, Urs L.

AU - Kinsella, Ian

AU - Zhou, Ding

AU - Rozsa, Marton

AU - Singh, Amrita

AU - Svoboda, Karel

AU - Paninski, Liam

AU - Cohen, Adam E.

N1 - Funding Information: M.E.X., Y.A., L.Z.F., U.L.B., and A.E.C. were supported by the Harvard Data Science Initiative , NIH grant R01MH117042 , and the Howard Hughes Medical Institute . I.K., D.Z., and L.P. were supported by NIH grant R01EB22913 . A.S., M.R., and K.S. were supported by the Howard Hughes Medical Institute . We thank C. Cai and A. Giovannuci for helpful discussions. We thank T. Kawashima, M. Ahrens, E. Jung, K. Piatkevich, and E. Boyden for zArchon1 zebrafish transgenics. The computations in this paper were run on the FASRC Cannon cluster supported by the FAS Division of the Science Research Computing Group at Harvard University. Funding Information: M.E.X. Y.A. L.Z.F. U.L.B. and A.E.C. were supported by the Harvard Data Science Initiative, NIH grant R01MH117042, and the Howard Hughes Medical Institute. I.K. D.Z. and L.P. were supported by NIH grant R01EB22913. A.S. M.R. and K.S. were supported by the Howard Hughes Medical Institute. We thank C. Cai and A. Giovannuci for helpful discussions. We thank T. Kawashima, M. Ahrens, E. Jung, K. Piatkevich, and E. Boyden for zArchon1 zebrafish transgenics. The computations in this paper were run on the FASRC Cannon cluster supported by the FAS Division of the Science Research Computing Group at Harvard University. M.E.X. wrote the code and analyzed the data. Y.A. acquired paQuasAr3-s and SomArchon1 data in hippocampus. L.Z.F. acquired SomArchon1 data in L1. U.L.B. acquired zArchon1 data in zebrafish spinal cord. I.K. D.Z. and L.P. contributed to the SGPMD-NMF algorithm. M.R. and A.S. acquired simultaneous patch-clamp and Voltron recordings in cortical L1. K.S. L.P. and A.E.C. supervised the research. M.E.X. L.P. and A.E.C. wrote the manuscript with input from all authors. A.E.C. is a co-founder of Q-State Biosciences. The other authors declare no competing interests. Publisher Copyright: © 2021 The Author(s)

PY - 2021/4/6

Y1 - 2021/4/6

N2 - The ability to probe the membrane potential of multiple genetically defined neurons simultaneously would have a profound impact on neuroscience research. Genetically encoded voltage indicators are a promising tool for this purpose, and recent developments have achieved a high signal-to-noise ratio in vivo with 1-photon fluorescence imaging. However, these recordings exhibit several sources of noise and signal extraction remains a challenge. We present an improved signal extraction pipeline, spike-guided penalized matrix decomposition-nonnegative matrix factorization (SGPMD-NMF), which resolves supra- and subthreshold voltages in vivo. The method incorporates biophysical and optical constraints. We validate the pipeline with simultaneous patch-clamp and optical recordings from mouse layer 1 in vivo and with simulated and composite datasets with realistic noise. We demonstrate applications to mouse hippocampus expressing paQuasAr3-s or SomArchon1, mouse cortex expressing SomArchon1 or Voltron, and zebrafish spines expressing zArchon1.

AB - The ability to probe the membrane potential of multiple genetically defined neurons simultaneously would have a profound impact on neuroscience research. Genetically encoded voltage indicators are a promising tool for this purpose, and recent developments have achieved a high signal-to-noise ratio in vivo with 1-photon fluorescence imaging. However, these recordings exhibit several sources of noise and signal extraction remains a challenge. We present an improved signal extraction pipeline, spike-guided penalized matrix decomposition-nonnegative matrix factorization (SGPMD-NMF), which resolves supra- and subthreshold voltages in vivo. The method incorporates biophysical and optical constraints. We validate the pipeline with simultaneous patch-clamp and optical recordings from mouse layer 1 in vivo and with simulated and composite datasets with realistic noise. We demonstrate applications to mouse hippocampus expressing paQuasAr3-s or SomArchon1, mouse cortex expressing SomArchon1 or Voltron, and zebrafish spines expressing zArchon1.

KW - signal extraction

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DO - 10.1016/j.celrep.2021.108954

M3 - Article

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JO - Cell Reports

JF - Cell Reports

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M1 - 108954

ER -

High-fidelity estimates of spikes and subthreshold waveforms from 1-photon voltage imaging in vivo

Abstract

Bibliographical note

Keywords

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