Granger causality analysis for calcium transients in neuronal networks, challenges and improvements

Abstract

One challenge in neuroscience is to understand how information flows between neurons in vivo to trigger specific behaviors. Granger causality (GC) has been proposed as a simple and effective measure for identifying dynamical interactions. At single-cell resolution however, GC analysis is rarely used compared to directionless correlation analysis. Here, we study the applicability of GC analysis for calcium imaging data in diverse contexts. We first show that despite underlying linearity assumptions, GC analysis successfully retrieves non-linear interactions in a synthetic network simulating intracellular calcium fluctuations of spiking neurons. We highlight the potential pitfalls of applying GC analysis on real in vivo calcium signals, and offer solutions regarding the choice of GC analysis parameters. We took advantage of calcium imaging datasets from motoneurons in embryonic zebrafish to show how the improved GC can retrieve true underlying information flow. Applied to the network of brainstem neurons of larval zebrafish, our pipeline reveals strong driver neurons in the locus of the mesencephalic locomotor region (MLR), driving target neurons matching expectations from anatomical and physiological studies. Altogether, this practical toolbox can be applied on in vivo population calcium signals to increase the selectivity of GC to infer flow of information across neurons.

Data availability

The current manuscript is a computational study, so no data have been generated for this manuscript. All data used in our manuscript have been pre- viously published (references [32, 33] in the manuscript). Modelling code is available on the github: https://github.com/statbiophys/zebrafishGCData files are available: https://zenodo.org/record/6774389#.Yr1Rm5PMKEs

The following previously published data sets were used

Article and author information

Author details

  1. Xiaowen Chen

    Laboratoire de physique de l'École normale supérieure, CNRS, Paris, France
    Competing interests
    No competing interests declared.
  2. Faustine Ginoux

    Spinal Sensory Signaling team, Institut du Cerveau, Paris, France
    Competing interests
    No competing interests declared.
  3. Martin Carbo-Tano

    Spinal Sensory Signaling team, Institut du Cerveau, Paris, France
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1936-7174
  4. Thierry Mora

    Laboratoire de physique de l'École normale supérieure, CNRS, Paris, France
    For correspondence
    thierry.mora@phys.ens.fr
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5456-9361
  5. Aleksandra M Walczak

    Laboratoire de physique de l'École normale supérieure, CNRS, Paris, France
    For correspondence
    aleksandra.walczak@phys.ens.fr
    Competing interests
    Aleksandra M Walczak, Senior editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2686-5702
  6. Claire Wyart

    Spinal Sensory Signaling team, Institut du Cerveau, Paris, France
    For correspondence
    claire.wyart@icm-institute.org
    Competing interests
    Claire Wyart, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1668-4975

Funding

European Research Council (COG 724208)

  • Aleksandra M Walczak

European Research Council (COG 101002870)

  • Claire Wyart

New York Stem Cell Foundation (NYSCF-R-NI39)

  • Claire Wyart

Human Frontier Science Program (RGP0063/2018)

  • Claire Wyart

Fondation pour la Recherche Médicale (FRM- EQU202003010612)

  • Claire Wyart

Fondation Bettencourt-Schueller (FBS-don-0031)

  • Claire Wyart

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Gordon J Berman, Emory University, United States

Version history

  1. Received: June 22, 2022
  2. Preprint posted: June 29, 2022 (view preprint)
  3. Accepted: February 6, 2023
  4. Accepted Manuscript published: February 7, 2023 (version 1)
  5. Version of Record published: March 15, 2023 (version 2)

Copyright

© 2023, Chen et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Xiaowen Chen
  2. Faustine Ginoux
  3. Martin Carbo-Tano
  4. Thierry Mora
  5. Aleksandra M Walczak
  6. Claire Wyart
(2023)
Granger causality analysis for calcium transients in neuronal networks, challenges and improvements
eLife 12:e81279.
https://doi.org/10.7554/eLife.81279

Share this article

https://doi.org/10.7554/eLife.81279

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