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.
Reviewing Editor
- 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
- 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.
Metrics
-
- 3,201
- views
-
- 559
- downloads
-
- 48
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Lactate is an energy substrate for rodent cortical neurons and enhances their firing activity
eLife 10:e71424.
https://doi.org/10.7554/eLife.71424
Further reading
-
- Neuroscience
The brain’s ability to appraise threats and execute appropriate defensive responses is essential for survival in a dynamic environment. Humans studies have implicated the anterior insular cortex (aIC) in subjective fear regulation and its abnormal activity in fear/anxiety disorders. However, the complex aIC connectivity patterns involved in regulating fear remain under investigated. To address this, we recorded single units in the aIC of freely moving male mice that had previously undergone auditory fear conditioning, assessed the effect of optogenetically activating specific aIC output structures in fear, and examined the organization of aIC neurons projecting to the specific structures with retrograde tracing. Single-unit recordings revealed that a balanced number of aIC pyramidal neurons’ activity either positively or negatively correlated with a conditioned tone-induced freezing (fear) response. Optogenetic manipulations of aIC pyramidal neuronal activity during conditioned tone presentation altered the expression of conditioned freezing. Neural tracing showed that non-overlapping populations of aIC neurons project to the amygdala or the medial thalamus, and the pathway bidirectionally modulated conditioned fear. Specifically, optogenetic stimulation of the aIC-amygdala pathway increased conditioned freezing, while optogenetic stimulation of the aIC-medial thalamus pathway decreased it. Our findings suggest that the balance of freezing-excited and freezing-inhibited neuronal activity in the aIC and the distinct efferent circuits interact collectively to modulate fear behavior.
-
- Neuroscience
Motor learning is often viewed as a unitary process that operates outside of conscious awareness. This perspective has led to the development of sophisticated models designed to elucidate the mechanisms of implicit sensorimotor learning. In this review, we argue for a broader perspective, emphasizing the contribution of explicit strategies to sensorimotor learning tasks. Furthermore, we propose a theoretical framework for motor learning that consists of three fundamental processes: reasoning, the process of understanding action–outcome relationships; refinement, the process of optimizing sensorimotor and cognitive parameters to achieve motor goals; and retrieval, the process of inferring the context and recalling a control policy. We anticipate that this ‘3R’ framework for understanding how complex movements are learned will open exciting avenues for future research at the intersection between cognition and action.
