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

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Article number108954
JournalCell Reports
Volume35
Issue number1
DOIs
StatePublished - 6 Apr 2021
Externally publishedYes

Keywords

  • signal extraction
  • voltage imaging

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology

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