Uncovering circuit mechanisms of current sinks and sources with biophysical simulations of primary visual cortex

  1. Atle E Rimehaug  Is a corresponding author
  2. Alexander J Stasik
  3. Espen Hagen
  4. Yazan N Billeh
  5. Josh H Siegle
  6. Kael Dai
  7. Shawn R Olsen
  8. Christof Koch
  9. Gaute T Einevoll
  10. Anton Arkhipov
  1. University of Oslo, Norway
  2. Allen Institute for Brain Science, United States
  3. Allen Institute, United States
  4. Norwegian University of Life Sciences, Norway

Abstract

​​Local field potential (LFP) recordings reflect the dynamics of the current source density (CSD) in brain tissue. The synaptic, cellular and circuit contributions to current sinks and sources are ill-understood. We investigated these in mouse primary visual cortex using public Neuropixels recordings and a detailed circuit model based on simulating the Hodgkin-Huxley dynamics of >50,000 neurons belonging to 17 cell types. The model simultaneously captured spiking and CSD responses and demonstrated a two-way dissociation: Firing rates are altered with minor effects on the CSD pattern by adjusting synaptic weights, and CSD is altered with minor effects on firing rates by adjusting synaptic placement on the dendrites. We describe how thalamocortical inputs and recurrent connections sculpt specific sinks and sources early in the visual response, whereas cortical feedback crucially alters them in later stages. These results establish quantitative links between macroscopic brain measurements (LFP/CSD) and microscopic biophysics-based understanding of neuron dynamics and show that CSD analysis provides powerful constraints for modeling beyond those from considering spikes.

Data availability

The files necessary to run simulations of the different model versions presented in the paper as well as data resulting from simulations of those model versions are publicly available in Dryad: https://doi.org/10.5061/dryad.k3j9kd5b8The experimental data set utilized is publicly available at: https://portal.brain-map.org/explore/circuits/visual-coding-neuropixelsThe code generated for data analysis and producing the figures in this manuscript is publicly available at: https://github.com/atleer/CINPLA_Allen_V1_analysis.git.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Atle E Rimehaug

    Department of Informatics, University of Oslo, Oslo, Norway
    For correspondence
    atleeri@ifi.uio.no
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8312-9875
  2. Alexander J Stasik

    Department of Physics, University of Oslo, Oslo, Norway
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1646-2472
  3. Espen Hagen

    Department of Physics, University of Oslo, Oslo, Norway
    Competing interests
    The authors declare that no competing interests exist.
  4. Yazan N Billeh

    MindScope Program, Allen Institute for Brain Science, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Josh H Siegle

    MindScope Program, Allen Institute, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7736-4844
  6. Kael Dai

    MindScope Program, Allen Institute, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Shawn R Olsen

    MindScope Program, Allen Institute, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9568-7057
  8. Christof Koch

    MindScope Program, Allen Institute, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Gaute T Einevoll

    Department of Physics, Norwegian University of Life Sciences, Ås, Norway
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5425-5012
  10. Anton Arkhipov

    MindScope Program, Allen Institute for Brain Science, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1106-8310

Funding

Simula School of Research

  • Atle E Rimehaug

European Union Horizon 2020 Research and Innovation program (785907)

  • Espen Hagen

European Union Horizon 2020 Research and Innovation program (945539)

  • Espen Hagen

Research Council of Norway (COBRA - project number 250128)

  • Alexander J Stasik

IKTPLUSS-IKT and Digital Innovation (300504)

  • Alexander J Stasik

National Institute of Neurological Disorders and Stroke (R01NS122742)

  • Yazan N Billeh
  • Josh H Siegle
  • Kael Dai
  • Shawn R Olsen
  • Christof Koch
  • Anton Arkhipov

National Institute of Biomedical Imaging and Bioengineering (R01EB029813)

  • Yazan N Billeh
  • Josh H Siegle
  • Kael Dai
  • Shawn R Olsen
  • Christof Koch
  • Anton Arkhipov

Allen Institute

  • Yazan N Billeh
  • Josh H Siegle
  • Kael Dai
  • Shawn R Olsen
  • Christof Koch
  • Anton Arkhipov

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

Reviewing Editor

  1. Tirin Moore, Howard Hughes Medical Institute, Stanford University, United States

Version history

  1. Preprint posted: February 25, 2022 (view preprint)
  2. Received: February 23, 2023
  3. Accepted: July 10, 2023
  4. Accepted Manuscript published: July 24, 2023 (version 1)
  5. Version of Record published: August 1, 2023 (version 2)
  6. Version of Record updated: August 11, 2023 (version 3)

Copyright

© 2023, Rimehaug 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. Atle E Rimehaug
  2. Alexander J Stasik
  3. Espen Hagen
  4. Yazan N Billeh
  5. Josh H Siegle
  6. Kael Dai
  7. Shawn R Olsen
  8. Christof Koch
  9. Gaute T Einevoll
  10. Anton Arkhipov
(2023)
Uncovering circuit mechanisms of current sinks and sources with biophysical simulations of primary visual cortex
eLife 12:e87169.
https://doi.org/10.7554/eLife.87169

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