Lactate is an energy substrate for rodent cortical neurons and enhances their firing activity
- CNRS, INSERM, Sorbonne Université, France
- CNRS, ESPCI Paris, France
- Goethe University Frankfurt, Germany
- Sorbonne Université, INSERM, CNRS, France
- Georg-August-University Goettingen, Germany
- Kyoto University, Japan
- 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
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.
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.
Reviewing Editor
- Marco Capogna, University of Aarhus, Denmark
Version history
- Preprint posted: May 17, 2021 (view preprint)
- Received: June 18, 2021
- Accepted: November 9, 2021
- Accepted Manuscript published: November 12, 2021 (version 1)
- 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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Lactate is an energy substrate for rodent cortical neurons and enhances their firing activity
eLife 10:e71424.
https://doi.org/10.7554/eLife.71424
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