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

Cell Rep. 2021 Apr 6;35(1):108954. doi: 10.1016/j.celrep.2021.108954.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology*
  • Algorithms
  • Animals
  • Computer Simulation
  • Hippocampus / physiology
  • Imaging, Three-Dimensional*
  • Mice, Transgenic
  • Photons*
  • Pyramidal Cells / physiology
  • Reproducibility of Results
  • Signal Transduction
  • Zebrafish