Lactate is an energy substrate for rodent cortical neurons and enhances their firing activity

  1. Anastassios Karagiannis
  2. Thierry Gallopin
  3. Alexandre Lacroix
  4. Fabrice Plaisier
  5. Juliette Piquet
  6. Hélène Geoffroy
  7. Régine Hepp
  8. Jérémie Naudé
  9. Benjamin Le Gac
  10. Richard Egger
  11. Bertrand Lambolez
  12. Dongdong Li
  13. Jean Rossier
  14. Jochen F Staiger
  15. Hiromi Imamura
  16. Susumu Seino
  17. Jochen Roeper
  18. Bruno Cauli  Is a corresponding author
  1. CNRS, INSERM, Sorbonne Université, France
  2. CNRS, ESPCI Paris, France
  3. Goethe University Frankfurt, Germany
  4. Sorbonne Université, INSERM, CNRS, France
  5. Georg-August-University Goettingen, Germany
  6. Kyoto University, Japan
  7. Kobe University Graduate School of Medicine, Japan

Abstract

Glucose is the mandatory fuel for the brain, yet the relative contribution of glucose and lactate for neuronal energy metabolism is unclear. We found that increased lactate, but not glucose concentration, enhances the spiking activity of neurons of the cerebral cortex. Enhanced spiking was dependent on ATP-sensitive potassium (KATP) channels formed with KCNJ11 and ABCC8 subunits, which we show are functionally expressed in most neocortical neuronal types. We also demonstrate the ability of cortical neurons to take-up and metabolize lactate. We further reveal that ATP is produced by cortical neurons largely via oxidative phosphorylation and only modestly by glycolysis. Our data demonstrate that in active neurons, lactate is preferred to glucose as an energy substrate, and that lactate metabolism shapes neuronal activity in the neocortex through KATP channels. Our results highlight the importance of metabolic crosstalk between neurons and astrocytes for brain function.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1 to 6.

Article and author information

Author details

  1. Anastassios Karagiannis

    CNRS, INSERM, Sorbonne Université, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Thierry Gallopin

    Brain Plasticity Unit, CNRS UMR 8249, CNRS, ESPCI Paris, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Alexandre Lacroix

    CNRS, INSERM, Sorbonne Université, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Fabrice Plaisier

    CNRS, INSERM, Sorbonne Université, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Juliette Piquet

    CNRS, INSERM, Sorbonne Université, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Hélène Geoffroy

    Brain Plasticity Unit, CNRS UMR 8249, CNRS, ESPCI Paris, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Régine Hepp

    CNRS, INSERM, Sorbonne Université, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Jérémie Naudé

    CNRS, INSERM, Sorbonne Université, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5781-6498
  9. Benjamin Le Gac

    CNRS, INSERM, Sorbonne Université, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  10. Richard Egger

    Institute for Neurophysiology, Goethe University Frankfurt, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
  11. Bertrand Lambolez

    Neuroscience Paris Seine - Institut de Biologie Paris Seine (NPS - IBPS), Sorbonne Université, INSERM, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0653-480X
  12. Dongdong Li

    CNRS, INSERM, Sorbonne Université, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  13. Jean Rossier

    CNRS, INSERM, Sorbonne Université, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1821-2135
  14. Jochen F Staiger

    Institute for Neuroanatomy, Georg-August-University Goettingen, Goettingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  15. Hiromi Imamura

    Graduate School of Biostudies, Kyoto University, Kyoto, Japan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1896-0443
  16. Susumu Seino

    Kobe University Graduate School of Medicine, Hyogo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  17. Jochen Roeper

    Institute for Neurophysiology, Goethe University Frankfurt, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2145-8742
  18. Bruno Cauli

    CNRS, INSERM, Sorbonne Université, Paris, France
    For correspondence
    bruno.cauli@upmc.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1471-4621

Funding

Human Frontier Science Program (RGY0070/2007)

  • Bruno Cauli

Agence Nationale de la Recherche (ANR 2011 MALZ 003 01)

  • Bruno Cauli

Fondation pour la Recherche Médicale (FDT20100920106)

  • Anastassios Karagiannis

Fondation pour la Recherche sur Alzheimer

  • Benjamin Le Gac

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

Reviewing Editor

  1. Marco Capogna, University of Aarhus, Denmark

Ethics

Animal experimentation: Wistar rats, C57BL/6RJ or Kcnj11-/- (B6.129P2-Kcnj11tm1Sse, backcrossed into C57BL6 over six generations) mice were used for all experiments in accordance with French regulations (Code Rural R214/87 to R214/130) and conformed to the ethical guidelines of both the directive 2010/63/EU of the European Parliament and of the Council and the French National Charter on the ethics of animal experimentation. A maximum of 3 rats or 5 mice were housed per cage and single animal housing was avoided. Male rats and mice of both genders were housed on a 12-hour light/dark cycle in a temperature-controlled (21-25{degree sign}C) room and were given food and water ad libitum. Animals were used for experimentation at 13-24 days of age.

Version history

  1. Preprint posted: May 17, 2021 (view preprint)
  2. Received: June 18, 2021
  3. Accepted: November 9, 2021
  4. Accepted Manuscript published: November 12, 2021 (version 1)
  5. Version of Record published: December 7, 2021 (version 2)

Copyright

© 2021, Karagiannis 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. Anastassios Karagiannis
  2. Thierry Gallopin
  3. Alexandre Lacroix
  4. Fabrice Plaisier
  5. Juliette Piquet
  6. Hélène Geoffroy
  7. Régine Hepp
  8. Jérémie Naudé
  9. Benjamin Le Gac
  10. Richard Egger
  11. Bertrand Lambolez
  12. Dongdong Li
  13. Jean Rossier
  14. Jochen F Staiger
  15. Hiromi Imamura
  16. Susumu Seino
  17. Jochen Roeper
  18. Bruno Cauli
(2021)
Lactate is an energy substrate for rodent cortical neurons and enhances their firing activity
eLife 10:e71424.
https://doi.org/10.7554/eLife.71424

Share this article

https://doi.org/10.7554/eLife.71424

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