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J Neurosci
2014 Feb 12;347:2605-17. doi: 10.1523/JNEUROSCI.4687-12.2014.
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On-site energy supply at synapses through monocarboxylate transporters maintains excitatory synaptic transmission.
Nagase M
,
Takahashi Y
,
Watabe AM
,
Kubo Y
,
Kato F
.
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ATP production through oxidative phosphorylation in the mitochondria is the most efficient way to provide energy to various energy-consuming activities of the neurons. These processes require a large amount of ATP molecules to be maintained. Of these, synaptic transmission is most energy consuming. Here we report that lactate transported through monocarboxylate transporters (MCTs) at excitatory synapses constitutively supports synaptic transmission, even under conditions in which a sufficient supply of glucose and intracellular ATP are present. We analyzed the effects of MCT inhibition on neuronal activities using whole-cell recordings in brain slices of rats in the nucleus of the solitary tract. MCT inhibitors (α-cyano-4-hydroxycinnamic acid (4-CIN), phloretin, and d-lactate) significantly decreased the amplitude of EPSCs without reducing release probability. Although 4-CIN significantly reduced currents mediated by heterologously expressed AMPA-Rs in oocytes (a novel finding in this study), the IC50 of the inhibitory effect on EPSC in brain slices was ∼3.8 times smaller than that on AMPA-R currents in oocytes. Removal of intracellular ATP significantly potentiated the inhibition of EPSC with 4-CIN in a manner that was counteracted by intracellular lactate addition. In addition, extracellular lactate rescued aglycemic suppression of EPSC, in a manner that was prevented by 4-CIN. Inhibition of MCTs also reduced NMDA-R-mediated EPSCs and, to a lesser extent, the IPSC. The reduction in EPSC amplitude by γ-d-glutamylglycine was enhanced by 4-CIN, suggesting also a decreased quantal content. We conclude that "on-site" astrocyte-neuron lactate transport to presynaptic and postsynaptic elements is necessary for the integrity of excitatory synaptic transmission.
Alle,
Energy-efficient action potentials in hippocampal mossy fibers.
2009, Pubmed
Alle,
Energy-efficient action potentials in hippocampal mossy fibers.
2009,
Pubmed
Attwell,
An energy budget for signaling in the grey matter of the brain.
2001,
Pubmed
Attwell,
Neuroenergetics and the kinetic design of excitatory synapses.
2005,
Pubmed
Atwood,
Diversification of synaptic strength: presynaptic elements.
2002,
Pubmed
Barros,
Glucose and lactate supply to the synapse.
2010,
Pubmed
Bergersen,
Selective postsynaptic co-localization of MCT2 with AMPA receptor GluR2/3 subunits at excitatory synapses exhibiting AMPA receptor trafficking.
2005,
Pubmed
Bergersen,
A novel postsynaptic density protein: the monocarboxylate transporter MCT2 is co-localized with delta-glutamate receptors in postsynaptic densities of parallel fiber-Purkinje cell synapses.
2001,
Pubmed
Blom,
Spatial distribution of Na+-K+-ATPase in dendritic spines dissected by nanoscale superresolution STED microscopy.
2011,
Pubmed
Briski,
In situ coexpression of glucose and monocarboxylate transporter mRNAs in metabolic-sensitive caudal dorsal vagal complex catecholaminergic neurons: transcriptional reactivity to insulin-induced hypoglycemia and caudal hindbrain glucose or lactate repletion during insulin-induced hypoglycemia.
2009,
Pubmed
Brown,
Astrocyte glycogen and brain energy metabolism.
2007,
Pubmed
Bélanger,
Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation.
2011,
Pubmed
Cataldo,
Cytochemical identification of cerebral glycogen and glucose-6-phosphatase activity under normal and experimental conditions. II. Choroid plexus and ependymal epithelia, endothelia and pericytes.
1986,
Pubmed
Erlichman,
Inhibition of monocarboxylate transporter 2 in the retrotrapezoid nucleus in rats: a test of the astrocyte-neuron lactate-shuttle hypothesis.
2008,
Pubmed
Flick,
Identification of putative mammalian D-lactate dehydrogenase enzymes.
2002,
Pubmed
Fremeau,
VGLUTs define subsets of excitatory neurons and suggest novel roles for glutamate.
2004,
Pubmed
Fujiwara,
Regulation of the desensitization and ion selectivity of ATP-gated P2X2 channels by phosphoinositides.
2006,
Pubmed
,
Xenbase
Halestrap,
The specificity and metabolic implications of the inhibition of pyruvate transport in isolated mitochondria and intact tissue preparations by alpha-Cyano-4-hydroxycinnamate and related compounds.
1975,
Pubmed
Halestrap,
The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation.
1999,
Pubmed
,
Xenbase
Hamilton,
Do astrocytes really exocytose neurotransmitters?
2010,
Pubmed
Hertz,
Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis.
2007,
Pubmed
Himmi,
Effects of lactate on glucose-sensing neurons in the solitary tract nucleus.
2001,
Pubmed
Ikemoto,
Glycolysis and glutamate accumulation into synaptic vesicles. Role of glyceraldehyde phosphate dehydrogenase and 3-phosphoglycerate kinase.
2003,
Pubmed
Ishii,
Identification and characterization of Cs(+) -permeable K(+) channel current in mouse cerebellar Purkinje cells in lobules 9 and 10 evoked by molecular layer stimulation.
2010,
Pubmed
,
Xenbase
Izumi,
Endogenous monocarboxylates sustain hippocampal synaptic function and morphological integrity during energy deprivation.
1997,
Pubmed
Kann,
Mitochondria and neuronal activity.
2007,
Pubmed
Kato,
Distinct modulation of evoked and spontaneous EPSCs by purinoceptors in the nucleus tractus solitarii of the rat.
2001,
Pubmed
Keceli,
Functional and structural identification of amino acid residues of the P2X2 receptor channel critical for the voltage- and [ATP]-dependent gating.
2009,
Pubmed
,
Xenbase
Lachamp,
Vesicular glutamate transporters type 1 and 2 expression in axon terminals of the rat nucleus of the solitary tract.
2006,
Pubmed
Laschet,
Glyceraldehyde-3-phosphate dehydrogenase is a GABAA receptor kinase linking glycolysis to neuronal inhibition.
2004,
Pubmed
Liu,
Variability of neurotransmitter concentration and nonsaturation of postsynaptic AMPA receptors at synapses in hippocampal cultures and slices.
1999,
Pubmed
Maekawa,
Regulation of the intracellular distribution, cell surface expression, and protein levels of AMPA receptor GluR2 subunits by the monocarboxylate transporter MCT2 in neuronal cells.
2009,
Pubmed
Matsuyama,
Food deprivation induces monocarboxylate transporter 2 expression in the brainstem of female rat.
2009,
Pubmed
McKenna,
Alpha-cyano-4-hydroxycinnamate decreases both glucose and lactate metabolism in neurons and astrocytes: implications for lactate as an energy substrate for neurons.
2001,
Pubmed
Nedergaard,
Artifact versus reality--how astrocytes contribute to synaptic events.
2012,
Pubmed
Negishi,
Geometric and functional architecture of visceral sensory microcircuitry.
2011,
Pubmed
Parsons,
ATP-sensitive potassium channel-mediated lactate effect on orexin neurons: implications for brain energetics during arousal.
2010,
Pubmed
Patil,
Lactate is a critical "sensed" variable in caudal hindbrain monitoring of CNS metabolic stasis.
2005,
Pubmed
Pellerin,
Activity-dependent regulation of energy metabolism by astrocytes: an update.
2007,
Pubmed
Pierre,
Monocarboxylate transporters in the central nervous system: distribution, regulation and function.
2005,
Pubmed
Pierre,
Linking supply to demand: the neuronal monocarboxylate transporter MCT2 and the alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid receptor GluR2/3 subunit are associated in a common trafficking process.
2009,
Pubmed
Randle,
Competitive inhibition by NBQX of kainate/AMPA receptor currents and excitatory synaptic potentials: importance of 6-nitro substitution.
1992,
Pubmed
,
Xenbase
Rose,
NMDA receptor-mediated Na+ signals in spines and dendrites.
2001,
Pubmed
Rothstein,
Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate.
1996,
Pubmed
Rouach,
Astroglial metabolic networks sustain hippocampal synaptic transmission.
2008,
Pubmed
Sakurai,
Synaptic adaptation to repeated hypoglycemia depends on the utilization of monocarboxylates in Guinea pig hippocampal slices.
2002,
Pubmed
Schäfer,
Molecular cloning and functional identification of mouse vesicular glutamate transporter 3 and its expression in subsets of novel excitatory neurons.
2002,
Pubmed
Sheng,
Mitochondrial transport in neurons: impact on synaptic homeostasis and neurodegeneration.
2012,
Pubmed
Shigetomi,
Action potential-independent release of glutamate by Ca2+ entry through presynaptic P2X receptors elicits postsynaptic firing in the brainstem autonomic network.
2004,
Pubmed
Suzuki,
Astrocyte-neuron lactate transport is required for long-term memory formation.
2011,
Pubmed
Taylor,
Effect of temperature on synaptic function after reduced oxygen and glucose in hippocampal slices.
1993,
Pubmed
Tekkök,
Transfer of glycogen-derived lactate from astrocytes to axons via specific monocarboxylate transporters supports mouse optic nerve activity.
2005,
Pubmed
Vilchez,
Mechanism suppressing glycogen synthesis in neurons and its demise in progressive myoclonus epilepsy.
2007,
Pubmed
Yamamoto,
Distinct target cell-dependent forms of short-term plasticity of the central visceral afferent synapses of the rat.
2010,
Pubmed
Yamazaki,
Blocker-resistant presynaptic voltage-dependent Ca2+ channels underlying glutamate release in mice nucleus tractus solitarii.
2006,
Pubmed
Zhang,
Na,K-ATPase activity regulates AMPA receptor turnover through proteasome-mediated proteolysis.
2009,
Pubmed
Zivkovic,
Regulation of AMPA receptor currents by mitochondrial ATP-sensitive K+ channels in anoxic turtle neurons.
2010,
Pubmed
Zucker,
Short-term synaptic plasticity.
2002,
Pubmed
