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Lactate induces synapse-specific potentiation on CA3 pyramidal cells of rat hippocampus

Neuronal activity within the physiologic range stimulates lactate production that, via metabolic pathways or operating through an array of G-protein-coupled receptors, regulates intrinsic excitability and synaptic transmission. The recent discovery that lactate exerts a tight control of ion channels...

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Autores principales: Herrera-López, Gabriel, Griego, Ernesto, Galván, Emilio J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660554/
https://www.ncbi.nlm.nih.gov/pubmed/33180836
http://dx.doi.org/10.1371/journal.pone.0242309
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author Herrera-López, Gabriel
Griego, Ernesto
Galván, Emilio J.
author_facet Herrera-López, Gabriel
Griego, Ernesto
Galván, Emilio J.
author_sort Herrera-López, Gabriel
collection PubMed
description Neuronal activity within the physiologic range stimulates lactate production that, via metabolic pathways or operating through an array of G-protein-coupled receptors, regulates intrinsic excitability and synaptic transmission. The recent discovery that lactate exerts a tight control of ion channels, neurotransmitter release, and synaptic plasticity-related intracellular signaling cascades opens up the possibility that lactate regulates synaptic potentiation at central synapses. Here, we demonstrate that extracellular lactate (1–2 mM) induces glutamatergic potentiation on the recurrent collateral synapses of hippocampal CA3 pyramidal cells. This potentiation is independent of lactate transport and further metabolism, but requires activation of NMDA receptors, postsynaptic calcium accumulation, and activation of a G-protein-coupled receptor sensitive to cholera toxin. Furthermore, perfusion of 3,5- dihydroxybenzoic acid, a lactate receptor agonist, mimics this form of synaptic potentiation. The transduction mechanism underlying this novel form of synaptic plasticity requires G-protein βγ subunits, inositol-1,4,5-trisphosphate 3-kinase, PKC, and CaMKII. Activation of these signaling cascades is compartmentalized in a synapse-specific manner since lactate does not induce potentiation at the mossy fiber synapses of CA3 pyramidal cells. Consistent with this synapse-specific potentiation, lactate increases the output discharge of CA3 neurons when recurrent collaterals are repeatedly activated during lactate perfusion. This study provides new insights into the cellular mechanisms by which lactate, acting via a membrane receptor, contributes to the memory formation process.
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spelling pubmed-76605542020-11-18 Lactate induces synapse-specific potentiation on CA3 pyramidal cells of rat hippocampus Herrera-López, Gabriel Griego, Ernesto Galván, Emilio J. PLoS One Research Article Neuronal activity within the physiologic range stimulates lactate production that, via metabolic pathways or operating through an array of G-protein-coupled receptors, regulates intrinsic excitability and synaptic transmission. The recent discovery that lactate exerts a tight control of ion channels, neurotransmitter release, and synaptic plasticity-related intracellular signaling cascades opens up the possibility that lactate regulates synaptic potentiation at central synapses. Here, we demonstrate that extracellular lactate (1–2 mM) induces glutamatergic potentiation on the recurrent collateral synapses of hippocampal CA3 pyramidal cells. This potentiation is independent of lactate transport and further metabolism, but requires activation of NMDA receptors, postsynaptic calcium accumulation, and activation of a G-protein-coupled receptor sensitive to cholera toxin. Furthermore, perfusion of 3,5- dihydroxybenzoic acid, a lactate receptor agonist, mimics this form of synaptic potentiation. The transduction mechanism underlying this novel form of synaptic plasticity requires G-protein βγ subunits, inositol-1,4,5-trisphosphate 3-kinase, PKC, and CaMKII. Activation of these signaling cascades is compartmentalized in a synapse-specific manner since lactate does not induce potentiation at the mossy fiber synapses of CA3 pyramidal cells. Consistent with this synapse-specific potentiation, lactate increases the output discharge of CA3 neurons when recurrent collaterals are repeatedly activated during lactate perfusion. This study provides new insights into the cellular mechanisms by which lactate, acting via a membrane receptor, contributes to the memory formation process. Public Library of Science 2020-11-12 /pmc/articles/PMC7660554/ /pubmed/33180836 http://dx.doi.org/10.1371/journal.pone.0242309 Text en © 2020 Herrera-López et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Herrera-López, Gabriel
Griego, Ernesto
Galván, Emilio J.
Lactate induces synapse-specific potentiation on CA3 pyramidal cells of rat hippocampus
title Lactate induces synapse-specific potentiation on CA3 pyramidal cells of rat hippocampus
title_full Lactate induces synapse-specific potentiation on CA3 pyramidal cells of rat hippocampus
title_fullStr Lactate induces synapse-specific potentiation on CA3 pyramidal cells of rat hippocampus
title_full_unstemmed Lactate induces synapse-specific potentiation on CA3 pyramidal cells of rat hippocampus
title_short Lactate induces synapse-specific potentiation on CA3 pyramidal cells of rat hippocampus
title_sort lactate induces synapse-specific potentiation on ca3 pyramidal cells of rat hippocampus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660554/
https://www.ncbi.nlm.nih.gov/pubmed/33180836
http://dx.doi.org/10.1371/journal.pone.0242309
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