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

Autor:	Emilio J. Galván, Ernesto Griego, Gabriel Herrera-López
Rok vydání:	2020
Předmět:	Lactate transport Male Physiology Action Potentials Toxicology Pathology and Laboratory Medicine Nervous System Hippocampus Synapse Rats Sprague-Dawley chemistry.chemical_compound Cell Signaling Animal Cells Medicine and Health Sciences Toxins Neurotransmitter Protein Kinase C Neurons Multidisciplinary Neuronal Plasticity Organic Compounds Pyramidal Cells Monosaccharides Brain Long-term potentiation CA3 Region Hippocampal Signaling Cascades Cell biology Electrophysiology Chemistry Physical Sciences NMDA receptor Medicine Anatomy Cellular Types Signal Transduction Research Article Cholera Toxin Ganglion Cells Science Toxic Agents Carbohydrates Neurophysiology Neurotransmission Receptors N-Methyl-D-Aspartate Membrane Potential Ca2+/calmodulin-dependent protein kinase Animals Lactic Acid Oxamic Acid Organic Chemistry Chemical Compounds Excitatory Postsynaptic Potentials Biology and Life Sciences Cell Biology Rats Glucose chemistry Cellular Neuroscience Synaptic plasticity Synapses Calcium Calcium-Calmodulin-Dependent Protein Kinase Type 2 Neuroscience
Zdroj:	PLoS ONE PLoS ONE, Vol 15, Iss 11, p e0242309 (2020)
ISSN:	1932-6203
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ef444f7d9f5f8f9dc2e89e537e91dd38 https://pubmed.ncbi.nlm.nih.gov/33180836 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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