1. Computational and Systems Biology
  2. Neuroscience
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Training deep neural density estimators to identify mechanistic models of neural dynamics

  1. Pedro J Gonçalves  Is a corresponding author
  2. Jan-Matthis Lueckmann  Is a corresponding author
  3. Michael Deistler  Is a corresponding author
  4. Marcel Nonnenmacher
  5. Kaan Öcal
  6. Giacomo Bassetto
  7. Chaitanya Chintaluri
  8. William F Podlaski
  9. Sara A Haddad
  10. Tim Vogels
  11. David S Greenberg
  12. Jakob H Macke  Is a corresponding author
  1. Center of Advanced European Studies and Research (caesar), Germany
  2. Technical University of Munich, Germany
  3. Mathematical Institute, Germany
  4. University of Oxford, United Kingdom
  5. Max-Planck Institute for Brain Research, Germany
  6. University of Tübingen, Germany
Research Article
  • Cited 12
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Cite this article as: eLife 2020;9:e56261 doi: 10.7554/eLife.56261

Abstract

Mechanistic modeling in neuroscience aims to explain observed phenomena in terms of underlying causes. However, determining which model parameters agree with complex and stochastic neural data presents a significant challenge. We address this challenge with a machine learning tool which uses deep neural density estimators- trained using model simulations- to carry out Bayesian inference and retrieve the full space of parameters compatible with raw data or selected data features. Our method is scalable in parameters and data features, and can rapidly analyze new data after initial training. We demonstrate the power and flexibility of our approach on receptive fields, ion channels, and Hodgkin-Huxley models. We also characterize the space of circuit configurations giving rise to rhythmic activity in the crustacean stomatogastric ganglion, and use these results to derive hypotheses for underlying compensation mechanisms. Our approach will help close the gap between data-driven and theory-driven models of neural dynamics.

Data availability

The contributions of the work are primarily the development and application of computational models, no new data has been obtained or is being published. All code and associated data will be shared in the GitHub repository accompanying the article.

The following previously published data sets were used

Article and author information

Author details

  1. Pedro J Gonçalves

    Max Planck Research Group Neural Systems Analysis, Center of Advanced European Studies and Research (caesar), Bonn, Germany
    For correspondence
    pedro.goncalves@caesar.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6987-4836
  2. Jan-Matthis Lueckmann

    Department of Electrical and Computer Engineering, Technical University of Munich, Munich, Germany
    For correspondence
    jan-matthis.lueckmann@tum.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4320-4663
  3. Michael Deistler

    Department of Electrical and Computer Engineering, Technical University of Munich, Munich, Germany
    For correspondence
    michael.deistler@tum.de
    Competing interests
    The authors declare that no competing interests exist.
  4. Marcel Nonnenmacher

    Department of Electrical and Computer Engineering, Technical University of Munich, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Kaan Öcal

    University of Bonn, Mathematical Institute, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8528-6858
  6. Giacomo Bassetto

    Max Planck Research Group Neural Systems Analysis, Center of Advanced European Studies and Research (caesar), Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Chaitanya Chintaluri

    Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4252-1608
  8. William F Podlaski

    Physiology Anatomy and Genetics, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6619-7502
  9. Sara A Haddad

    Neural Systems and Coding, Max-Planck Institute for Brain Research, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. Tim Vogels

    Neural Systems and Coding, Max-Planck Institute for Brain Research, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
  11. David S Greenberg

    Department of Electrical and Computer Engineering, Technical University of Munich, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  12. Jakob H Macke

    Excellence Cluster Machine Learning, University of Tübingen, Tübingen, Germany
    For correspondence
    Jakob.Macke@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5154-8912

Funding

Deutsche Forschungsgemeinschaft (SFB~1233)

  • Jan-Matthis Lueckmann
  • Marcel Nonnenmacher
  • Giacomo Bassetto
  • Jakob H Macke

Deutsche Forschungsgemeinschaft (SFB~1089)

  • Pedro J Gonçalves
  • Jakob H Macke

Deutsche Forschungsgemeinschaft (SPP~2041)

  • Jakob H Macke

Bundesministerium für Bildung und Forschung (01IS18052 A-D)

  • Michael Deistler
  • Marcel Nonnenmacher
  • Jakob H Macke

Wellcome Trust and the Royal Society (WT100000)

  • William F Podlaski
  • Tim Vogels

H2020 European Research Council (SYNAPSEEK)

  • Chaitanya Chintaluri
  • William F Podlaski
  • Tim Vogels

Wellcome Trust Senior Research Fellowship (214316/Z/18/Z)

  • Tim Vogels

UK Research and Innovation, Biotechnology and Biological Sciences Research Council (UKRI-BBSRC BB/N019512/1)

  • Chaitanya Chintaluri

Deutsche Forschungsgemeinschaft (Germany's Excellence Strategy - EXC-Number 2064/1 610 - Project number 390727645)

  • Jakob H Macke

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

Reviewing Editor

  1. Timothy O'Leary, University of Cambridge, United Kingdom

Publication history

  1. Received: February 21, 2020
  2. Accepted: September 16, 2020
  3. Accepted Manuscript published: September 17, 2020 (version 1)
  4. Accepted Manuscript updated: September 18, 2020 (version 2)
  5. Version of Record published: October 22, 2020 (version 3)

Copyright

© 2020, Gonçalves 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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