Simultaneous Denoising, Deconvolution, and Demixing of Calcium Imaging Data

Neuron. 2016 Jan 20;89(2):285-99. doi: 10.1016/j.neuron.2015.11.037. Epub 2016 Jan 7.

Abstract

We present a modular approach for analyzing calcium imaging recordings of large neuronal ensembles. Our goal is to simultaneously identify the locations of the neurons, demix spatially overlapping components, and denoise and deconvolve the spiking activity from the slow dynamics of the calcium indicator. Our approach relies on a constrained nonnegative matrix factorization that expresses the spatiotemporal fluorescence activity as the product of a spatial matrix that encodes the spatial footprint of each neuron in the optical field and a temporal matrix that characterizes the calcium concentration of each neuron over time. This framework is combined with a novel constrained deconvolution approach that extracts estimates of neural activity from fluorescence traces, to create a spatiotemporal processing algorithm that requires minimal parameter tuning. We demonstrate the general applicability of our method by applying it to in vitro and in vivo multi-neuronal imaging data, whole-brain light-sheet imaging data, and dendritic imaging data.

Publication types

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

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Calcium / analysis
  • Calcium / metabolism*
  • Dendrites / chemistry
  • Dendrites / metabolism
  • Fluorescent Dyes / analysis
  • Fluorescent Dyes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence / methods*
  • Neurons / chemistry
  • Neurons / metabolism*
  • Statistics as Topic / methods*

Substances

  • Fluorescent Dyes
  • Calcium