Inferring Neuronal Dynamics from Calcium Imaging Data Using Biophysical Models and Bayesian Inference

PLoS Comput Biol. 2016 Feb 19;12(2):e1004736. doi: 10.1371/journal.pcbi.1004736. eCollection 2016 Feb.

Abstract

Calcium imaging has been used as a promising technique to monitor the dynamic activity of neuronal populations. However, the calcium trace is temporally smeared which restricts the extraction of quantities of interest such as spike trains of individual neurons. To address this issue, spike reconstruction algorithms have been introduced. One limitation of such reconstructions is that the underlying models are not informed about the biophysics of spike and burst generations. Such existing prior knowledge might be useful for constraining the possible solutions of spikes. Here we describe, in a novel Bayesian approach, how principled knowledge about neuronal dynamics can be employed to infer biophysical variables and parameters from fluorescence traces. By using both synthetic and in vitro recorded fluorescence traces, we demonstrate that the new approach is able to reconstruct different repetitive spiking and/or bursting patterns with accurate single spike resolution. Furthermore, we show that the high inference precision of the new approach is preserved even if the fluorescence trace is rather noisy or if the fluorescence transients show slow rise kinetics lasting several hundred milliseconds, and inhomogeneous rise and decay times. In addition, we discuss the use of the new approach for inferring parameter changes, e.g. due to a pharmacological intervention, as well as for inferring complex characteristics of immature neuronal circuits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Bayes Theorem
  • CA3 Region, Hippocampal / cytology
  • CA3 Region, Hippocampal / metabolism
  • Calcium / metabolism*
  • Calcium Signaling / physiology*
  • Cells, Cultured
  • Computational Biology
  • Mice
  • Mice, Inbred C57BL
  • Models, Neurological*
  • Molecular Imaging
  • Neurons / physiology*

Substances

  • Calcium

Grants and funding

This work was supported by the German Research Foundation and the Open Access Publication Funds of the TU Dresden, the Priority Program 1665 (HO 2156/3-1, KI 1816/1-1 and KI 1638/3-1), the Collaborative Research Center/Transregio 166 of the German Research Foundation (TRR 166/1 B3 to KH and KK), the Research Group FO 1738 (WI 830/10-2 to KH), the Federal Ministry of Education and Research (01GQ0923 to KH) and the Interdisciplinary Centre for Clinical Research Jena (to KK and KH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.