1. Neuroscience
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A parameter-free statistical test for neuronal responsiveness

  1. Jorrit Steven Montijn  Is a corresponding author
  2. Koen Seignette
  3. Marcus H Howlett
  4. J Leonie Cazemier
  5. Maarten Kamermans
  6. Christiaan Nicolaas Levelt
  7. J Alexander Heimel  Is a corresponding author
  1. Royal Dutch Academy for Arts and Sciences, Netherlands
  2. Netherlands Institute for Neuroscience, Netherlands
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Cite this article as: eLife 2021;10:e71969 doi: 10.7554/eLife.71969

Abstract

Neurophysiological studies depend on a reliable quantification of whether and when a neuron responds to stimulation. Simple methods to determine responsiveness require arbitrary parameter choices, such as binning size, while more advanced model-based methods require fitting and hyperparameter tuning. These parameter choices can change the results, which invites bad statistical practice and reduces the replicability. New recording techniques that yield increasingly large numbers of cells would benefit from a test for cell-inclusion that requires no manual curation. Here, we present the parameter-free ZETA-test, which outperforms t-tests, ANOVAs, and renewal-process-based methods by including more cells at a similar false-positive rate. We show that our procedure works across brain regions and recording techniques, including calcium imaging and Neuropixels data. Furthermore, in illustration of the method, we show in mouse visual cortex that 1) visuomotor-mismatch and spatial location are encoded by different neuronal subpopulations; and 2) optogenetic stimulation of VIP cells leads to early inhibition and subsequent disinhibition.

Data availability

As stated in the manuscript, open-source code for the ZETA-test is available at https://github.com/JorritMontijn/ZETA and https://github.com/JorritMontijn/zetapyFurthermore, code to reproduce the ZETA benchmarks are available at https://github.com/JorritMontijn/ZETA_analysis_repositoryThe Neuropixels data are annotated and available here: https://datadryad.org/stash/dataset/doi:10.5061/dryad.6djh9w108

The following data sets were generated
    1. Montijn JS
    (2020) ZETA benchmarking neuropixels data
    Dryad Digital Repository, doi:10.5061/dryad.6djh9w108.
The following previously published data sets were used
    1. Allen Brain Insitute
    (2019) Ecephys
    https://portal.brain-map.org/explore/circuits/visual-coding-neuropixels.

Article and author information

Author details

  1. Jorrit Steven Montijn

    Netherlands Institute for Neuroscience, Royal Dutch Academy for Arts and Sciences, Amsterdam, Netherlands
    For correspondence
    jsmontijn@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5621-090X
  2. Koen Seignette

    Netherlands Institute for Neuroscience, Royal Dutch Academy for Arts and Sciences, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  3. Marcus H Howlett

    Netherlands Institute for Neuroscience, Royal Dutch Academy for Arts and Sciences, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9620-8014
  4. J Leonie Cazemier

    Netherlands Institute for Neuroscience, Royal Dutch Academy for Arts and Sciences, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. Maarten Kamermans

    Retinal Signal Processing, Netherlands Institute for Neuroscience, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0847-828X
  6. Christiaan Nicolaas Levelt

    Molecular Visual Plasticity, Netherlands Institute for Neuroscience, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  7. J Alexander Heimel

    Netherlands Institute for Neuroscience, Royal Dutch Academy for Arts and Sciences, Amsterdam, Netherlands
    For correspondence
    a.heimel@nin.knaw.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5291-4184

Funding

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

Ethics

Animal experimentation: All experiments were approved by the animal ethics committee of the Royal Netherlands Academy of Arts and Sciences, in compliance with all relevant ethical regulations. Animals received anesthetics and analgesics where applicable, such as during surgeries, and every effort was made to minimize animal suffering.

Reviewing Editor

  1. Mark CW van Rossum, University of Nottingham, United Kingdom

Publication history

  1. Received: July 6, 2021
  2. Accepted: September 22, 2021
  3. Accepted Manuscript published: September 27, 2021 (version 1)

Copyright

© 2021, Montijn 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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