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
-
larval motoneuron datahttps://zenodo.org/record/6774389#.Yr1Rm5PMKEs.
-
hinbrain locomotion datahttps://zenodo.org/record/6774389#.Yr1Rm5PMKEs.
Article and author information
Author details
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
- Gordon J Berman, Emory University, United States
Version history
- Received: June 22, 2022
- Preprint posted: June 29, 2022 (view preprint)
- Accepted: February 6, 2023
- Accepted Manuscript published: February 7, 2023 (version 1)
- 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.
Metrics
-
- 1,694
- Page views
-
- 237
- Downloads
-
- 4
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Neuroscience
Cortical folding is an important feature of primate brains that plays a crucial role in various cognitive and behavioral processes. Extensive research has revealed both similarities and differences in folding morphology and brain function among primates including macaque and human. The folding morphology is the basis of brain function, making cross-species studies on folding morphology important for understanding brain function and species evolution. However, prior studies on cross-species folding morphology mainly focused on partial regions of the cortex instead of the entire brain. Previously, our research defined a whole-brain landmark based on folding morphology: the gyral peak. It was found to exist stably across individuals and ages in both human and macaque brains. Shared and unique gyral peaks in human and macaque are identified in this study, and their similarities and differences in spatial distribution, anatomical morphology, and functional connectivity were also dicussed.
-
- Neuroscience
Complex skills like speech and dance are composed of ordered sequences of simpler elements, but the neuronal basis for the syntactic ordering of actions is poorly understood. Birdsong is a learned vocal behavior composed of syntactically ordered syllables, controlled in part by the songbird premotor nucleus HVC (proper name). Here, we test whether one of HVC’s recurrent inputs, mMAN (medial magnocellular nucleus of the anterior nidopallium), contributes to sequencing in adult male Bengalese finches (Lonchura striata domestica). Bengalese finch song includes several patterns: (1) chunks, comprising stereotyped syllable sequences; (2) branch points, where a given syllable can be followed probabilistically by multiple syllables; and (3) repeat phrases, where individual syllables are repeated variable numbers of times. We found that following bilateral lesions of mMAN, acoustic structure of syllables remained largely intact, but sequencing became more variable, as evidenced by ‘breaks’ in previously stereotyped chunks, increased uncertainty at branch points, and increased variability in repeat numbers. Our results show that mMAN contributes to the variable sequencing of vocal elements in Bengalese finch song and demonstrate the influence of recurrent projections to HVC. Furthermore, they highlight the utility of species with complex syntax in investigating neuronal control of ordered sequences.