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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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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. |
format | Online Article Text |
id | pubmed-7660554 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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