Abstract
Lactate is increasingly described as an energy substrate of the brain. Beside this still debated metabolic role, lactate may have other effects on brain cells. Here, we describe lactate as a neuromodulator, able to influence the activity of cortical neurons. Neuronal excitability of mouse primary neurons was monitored by calcium imaging. When applied in conjunction with glucose, lactate induced a decrease in the spontaneous calcium spiking frequency of neurons. The effect was reversible and concentration dependent (IC50 ∼4.2 mM). To test whether lactate effects are dependent on energy metabolism, we applied the closely related substrate pyruvate (5 mM) or switched to different glucose concentrations (0.5 or 10 mM). None of these conditions reproduced the effect of lactate. Recently, a Gi protein-coupled receptor for lactate called HCA1 has been introduced. To test if this receptor is implicated in the observed lactate sensitivity, we incubated cells with pertussis toxin (PTX) an inhibitor of Gi-protein. PTX prevented the decrease of neuronal activity by L-lactate. Moreover 3,5-dyhydroxybenzoic acid, a specific agonist of the HCA1 receptor, mimicked the action of lactate. This study indicates that lactate operates a negative feedback on neuronal activity by a receptor-mediated mechanism, independent from its intracellular metabolism.
Citation: Bozzo L, Puyal J, Chatton J-Y (2013) Lactate Modulates the Activity of Primary Cortical Neurons through a Receptor-Mediated Pathway. PLoS ONE 8(8):
e71721.
https://doi.org/10.1371/journal.pone.0071721
Editor: Thierry Amédée, Centre national de la recherche scientifique, University of Bordeaux, France
Received: May 29, 2013; Accepted: July 10, 2013; Published: August 12, 2013
Copyright: © 2013 Bozzo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by grant #31003A-135720 from the Swiss National Science Foundation to JY Chatton as well as by the Swiss League Against Epilepsy. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Description
This study indicates that lactate operates a negative feedback on neuronal activity by a receptor-mediated mechanism.