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
Affiliations
Michael E. Xie
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
Yoav Adam
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
Linlin Z. Fan
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
Urs L. Böhm
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
Ian Kinsella
Department of Statistics, Columbia University, New York, NY 10027, USA
Ding Zhou
Department of Statistics, Columbia University, New York, NY 10027, USA
Marton Rozsa
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA
Amrita Singh
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21231, USA
Karel Svoboda
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA
Liam Paninski
Department of Statistics, Columbia University, New York, NY 10027, USA; Corresponding author
Adam E. Cohen
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Corresponding author
Summary: 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.
