The DOI matches its Crossref record; 68 of the 71 references it cites were found in a registry or an index; none of the 35 sources its claims cite is checked for support yet.
Neuronal Stimulation Triggers Neuronal Glycolysis and Not Lactate Uptake
Open accessAbstract
SUMMARY Proper brain function requires a substantial energy supply, up to 20% of whole body energy in humans, and brain activation produces large dynamic variations in energy demand. While local increases in cerebral blood flow are well known, the cellular responses to energy demand are controversial. During brain excitation, glycolysis of glucose to lactate temporarily exceeds the rate of mitochondrial fuel oxidation; although the increased energy demand occurs mainly within neurons, some have suggested this glycolysis occurs mainly in astrocytes, which then shuttle lactate to neurons as their primary fuel. Using metabolic biosensors in acute hippocampal slices and brains of awake mice, we find that neuronal metabolic responses to stimulation do not depend on astrocytic stimulation by glutamate release, nor do they require neuronal uptake of lactate; instead they reflect increased direct glucose consumption by neurons. Neuronal glycolysis temporarily outstrips oxidative metabolism, and provides a rapid response to increased energy demand.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Using genetically encoded metabolic biosensors in acute hippocampal slices and awake mouse cortex, this paper finds that neuronal stimulation raises cytosolic NADH:NAD+ via increased neuronal glycolysis, not via astrocyte-derived lactate uptake. The results contradict a stimulation-dependent astrocyte-neuron lactate shuttle and support direct neuronal glucose consumption as a rapid metabolic response.
Key findings
- Synaptic stimulation of dentate granule neurons produced a ~2-fold rise in cytosolic NADH:NAD+ (Peredox lifetime 1.73 ± 0.01 ns at baseline to 1.88 ± 0.01 ns stimulated; mean ± SEM, n=166 neurons), lasting about 3 minutes and correlating with Ca2+ responses.
- Blocking postsynaptic glutamate receptors abolished the neuronal NADH transient, and antidromic stimulation still produced similar transients, indicating glutamate stimulation of astrocytes is neither sufficient nor necessary.
- MCT inhibition with AR-C155858 reduced the neuronal response to exogenous lactate to 27% ± 2% of control (n=36 neurons) but did not abolish—and actually increased—the stimulation-induced NADH transient (95% CI 1.23- to 1.34-fold larger). LDH inhibition reduced exogenous lactate responses by 78% ± 3% but increased stimulation-induced NADH transients by 37% ± 5% (n=54 neurons).
- In awake mice, whisker stimulation produced ~4–5 minute NADH transients in responsive S1-BF neurons, with a smaller typical increase (~33% over resting); MCT inhibition reduced exogenous lactate responses by 85.3% ± 6.3% (n=59 neurons in 6 animals) but did not diminish whisker-stimulation NADH transients.
- Neuronal intracellular glucose showed stimulation-induced dips that became larger with partial glucose transport inhibition and were reduced by MCT inhibition; glycolysis inhibition with iodoacetic acid greatly reduced NADH transients.
Methods
- Acute mouse hippocampal slices and awake, unanesthetized mice with cranial windows; C57BL/6NCrl mice, including postnatal day 1 viral injections for hippocampal sensors and adult mice for cortical imaging.
- Two-photon fluorescence lifetime imaging of genetically encoded biosensors: Peredox for cytosolic NADH:NAD+, RCaMP1h for Ca2+, SweetieTS for glucose, Laconic for lactate, and pHRed for pH.
- Stimulation via electrical synaptic or antidromic stimulation in slices and 10-second 5 Hz whisker stimulation in vivo; pharmacology included NBQX/D-AP5, AR-C155858, GSK-2837808A, iodoacetic acid, cytochalasin B, and aminooxyacetate.
Limitations
- The paper states that because experiments used optical signals from neuronal cell bodies, it cannot exclude ANLS activity at synaptic terminals; it also cannot exclude some contribution of mitochondrial NADH shuttles to the NADH transients.
- The paper states that the relative contributions of glycolysis and oxidative phosphorylation to immediate neuronal energy demands remain unknown.
- The text notes technical caveats: Laconic has shallow lactate dependence and pH sensitivity, producing uncertainty in absolute lactate concentrations; AOA’s small effect could partly reflect alanine transaminase inhibition; and in vivo drug delivery through the permeable window required higher concentrations and longer times than in slices.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
25 Own interpretation · 22 Not checked yet · 21 Own result · 8 Own method · 2 No basis given
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Stimulation-induced transients in NADHCYT were not unique to the in vitro hippocampal slice preparation, but were also observed in a more natural in vivo situation, in the brains of awake, unanesthetized mice.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Similar neuronal cytosolic NADH transients occur in vivo with normal sensory stimulation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As for the in vitro case, the size of the NADHCYT transients was well-correlated with the Ca2+ response even for small responses (Figure 7C).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Similar neuronal cytosolic NADH transients occur in vivo with normal sensory stimulation
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Indeed, we found that application of MCT inhibitor to the slice did inhibit the stimulation-induced dips reported by the glucose sensor (Fig 5C, D).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Cytosolic NADH transients reflect increased neuronal glycolysis upon stimulation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Recording from many neurons, we observed a wide range of both Ca2+ and NADHCYT responses, but the two were well-correlated even for the smallest responses (Fig. 1D)”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Stimulation produces transient increases of cytosolic NADH:NAD+ in individual neurons
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There was only a small reduction (~10%) in the transients in the presence of AOA, relative to the slight increase in parallel controls with pyruvate (Fig. 6C, Suppl. Fig. S6).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Transients in cytosolic NADH do not simply reflect mitochondrial NAD(P)H transients
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The increase in cytosolic NADH:NAD+ ratio (hereafter referred to as NADHCYT) was quite substantial, with 60 stimuli typically producing a change from a baseline ratio of ~1:1000 up to a stimulated ratio of ~1:500, a ~2-fold change (corresponding to a Peredox LT of 1.73 ± 0.01 ns at baseline and 1.88 ± 0.01 ns when stimulated; mean ± SEM, n=166 neurons).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Stimulation produces transient increases of cytosolic NADH:NAD+ in individual neurons
plaindirectn = 166- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the presence of the MCT inhibitor, the NADHCYT response to direct application of exogenous lactate was much smaller (27% ± 2% of the original response, mean ± SEM, n=36 neurons), as expected if lactate uptake is mostly blocked.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Lactate import does not contribute to neuronal NADHCYT transients
plaindirectn = 36- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Upon brief synaptic stimulation of the DGNs by electrical stimulation in the molecular layer of the dentate gyrus (60 brief pulses), there was a prominent and reliable elevation of the cytosolic NADH:NAD+ ratio for a period of about 3 minutes (Figure 1A–C).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Stimulation produces transient increases of cytosolic NADH:NAD+ in individual neurons
plaindirectn = 166- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Next we applied the MCT inhibitor AR-C155858 (2 μM), and observed a small decline in the resting NADHCYT”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Lactate import does not contribute to neuronal NADHCYT transients
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“With application of the MCT inhibitor, there was no significant change in these neuronal intracellular [lactate] transients (Fig. 3G)”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Lactate import does not contribute to neuronal NADHCYT transients
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Application of AOA (10 mM) to hippocampal slices produced a prompt, large increase in NADHCYT (Fig. 6A) as expected from inhibition of a major contributor to cytosolic NADH recycling.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Transients in cytosolic NADH do not simply reflect mitochondrial NAD(P)H transients
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The maximal changes in NAD(P)H autofluorescence are typically much smaller (5–10%) than the changes we observe here using Peredox, employing comparable stimuli.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > The NADH biosensor reports metabolic transients specifically in neuronal cytosol
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We saw reproducible increases in the Laconic signal of DGNs with synaptic stimulation, corresponding to an increase in neuronal intracellular [lactate] (Fig. 3G, left).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Lactate import does not contribute to neuronal NADHCYT transients
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Despite the relative absence of glutamate release, we observed that antidromic stimulation produced NADHCYT transients in the DGN cell bodies very similar to those produced by synaptic stimulation (Fig 2E, F)”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Astrocyte stimulation by glutamate is neither sufficient nor necessary for neuronal NADH transients
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Our results argue that neurons are themselves a site of this increased glycolysis”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Transient aerobic glycolysis may provide a rapid first response to energy resupply, followed by the higher capacity response by oxidative phosphorylation
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Most of the experimental support for the ANLS has come from separate experiments on neurons and astrocytes, both conducted in cell culture conditions (Pellerin et al., 2007).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > INTRODUCTION
What the sources say
- Not checked yetcites Pellerin et al., 2007 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In vivo measurements to learn which cell type shows greater stimulated uptake of glucose analogs have given conflicting results (Chuquet et al., 2010; Lundgaard et al., 2015)”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > INTRODUCTION
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“However, with brain activation, glucose consumption increases much more than oxygen consumption (Fox and Raichle, 1986; Fox et al., 1988).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > INTRODUCTION
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Despite the relative absence of glutamate release, we observed that antidromic stimulation produced NADHCYT transients in the DGN cell bodies very similar to those produced by synaptic stimulation (Fig 2E, F), showing that glutamate stimulation of astrocytes is not required for the transients.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Astrocyte stimulation by glutamate is neither sufficient nor necessary for neuronal NADH transients
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Under these conditions, glutamate is still released from the presynaptic terminals and will be transported into astrocytes, and signaling through metabotropic glutamate receptors (GPCRs) is still intact, but these effects were not sufficient to produce an NADHCYT transient in the neurons.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Astrocyte stimulation by glutamate is neither sufficient nor necessary for neuronal NADH transients
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In either case, the contribution of the MAS to the NADHCYT transients appears to be minor.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Transients in cytosolic NADH do not simply reflect mitochondrial NAD(P)H transients
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results suggest that the neuronal NADHCYT transient may be produced by a transient increase in the rate of neuronal glycolysis.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Cytosolic NADH transients reflect increased neuronal glycolysis upon stimulation
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These NADHCYT signals are distinct from the autofluorescence signal referred to as NAD(P)H”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > The NADH biosensor reports metabolic transients specifically in neuronal cytosol
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The fluorescence lifetime (LT) of the sensor protein, measured in nanoseconds, gives a direct report of sensor occupancy and thus of the cytosolic NADH:NAD+ ratio (Mongeon et al., 2016).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Stimulation produces transient increases of cytosolic NADH:NAD+ in individual neurons
What the sources say
- Not checked yetcites Mongeon et al., 2016 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The Peredox biosensor is expressed in the cytosol and not targeted to mitochondria.
In the paper
“This argues that the two effects are mechanistically connected, and thus it argues against the idea that the glucose dips result from a reported activity-induced decrease in glucose transport (Porras et al., 2004).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Cytosolic NADH transients reflect increased neuronal glycolysis upon stimulation
What the sources say
- Not checked yetcites Porras et al., 2004 source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Neuronal NADH:NAD+ ratio is controlled by three major processes (Fig. 1E): glycolysis, lactate dehydrogenase activity, and mitochondrial NADH shuttles (Salway, 2004; in neurons, mainly the malate-aspartate shuttle, McKenna et al., 2006)”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Stimulation produces transient increases of cytosolic NADH:NAD+ in individual neurons
What the sources say
- Not checked yetcites Salway, 2004
- Not checked yetcites McKenna et al., 2006 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The conclusion that the NADHCYT transients are produced by a transient increase in glycolysis is also supported by the substantial inhibition of the transients by IAA treatment, which inhibits glycolysis (Figure 4).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Coordinated dips in neuronal [glucose] and increases in NADHCYT point to increased glycolysis after stimulation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These experimental results are incompatible with the hypothesis of lactate shuttling from astrocytes to neurons during stimulation.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Astrocyte-to-neuron lactate shuttling may occur at rest, but not during neuronal stimulation
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Despite the fact that both glycolysis and oxidative metabolism are elevated after stimulation, there is ample evidence that immediately after brain activation, oxygen consumption does not rise commensurate with the increases in blood flow and glucose consumption.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Transient aerobic glycolysis may provide a rapid first response to energy resupply, followed by the higher capacity response by oxidative phosphorylation
What the sources say
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Measurements of oxygen levels in brain slices indicate that oxygen consumption does increase promptly in response to stimulation (Hall et al., 2012; Ivanov et al., 2014)”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Transient aerobic glycolysis may provide a rapid first response to energy resupply, followed by the higher capacity response by oxidative phosphorylation
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The large stimulation-induced increase in NADHCYT that we observe using the Peredox sensor indicates that the production of NADH from glycolysis exceeds the rate of NADH shuttling to mitochondria.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Transient aerobic glycolysis may provide a rapid first response to energy resupply, followed by the higher capacity response by oxidative phosphorylation
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The Peredox biosensor is expressed in the cytosol and not targeted to mitochondria.
- Rests on an assumption: NADH does not pass through mitochondrial membranes.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, the rise in NADH is almost certainly accompanied by an increase in the lactate/pyruvate ratio, due to the rapid action of lactate dehydrogenase that serves to recycle NAD+ for use in further glycolysis.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Transient aerobic glycolysis may provide a rapid first response to energy resupply, followed by the higher capacity response by oxidative phosphorylation
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We attribute this dip to an increased rate of neuronal glucose consumption that exceeds any increase in glucose uptake.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Coordinated dips in neuronal [glucose] and increases in NADHCYT point to increased glycolysis after stimulation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While we cannot exclude some contribution of the mitochondrial NADH shuttles to producing the NADHCYT transients, it appears that glycolysis plays a dominant role.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Coordinated dips in neuronal [glucose] and increases in NADHCYT point to increased glycolysis after stimulation
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The failure of the MCT inhibitor to abolish (or even diminish) the stimulated rise in neuronal NADHCYT, despite its ability to nearly abolish the direct response to exogenous lactate, demonstrates conclusively that the neuronal transients in NADHCYT are not produced by lactate import.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Lactate import does not contribute to neuronal NADHCYT transients
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“The NAD(P)H autofluorescence is almost certainly dominated by mitochondrial NADH (Brennan et al., 2006; Shuttleworth, 2010; Berndt et al., 2015).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > The NADH biosensor reports metabolic transients specifically in neuronal cytosol
What the sources say
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This picture is bolstered by our observation that NADHCYT actually rises more when the movement of lactate across the plasma membrane (via MCTs) is blocked -- suggesting that conversion of pyruvate to lactate and export of lactate are normally required to recycle NAD+ and permit a continued high rate of glycolysis.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Transient aerobic glycolysis may provide a rapid first response to energy resupply, followed by the higher capacity response by oxidative phosphorylation
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This result is opposite from what would be expected if the dips had been caused by a dip in the extracellular glucose concentration, secondary to increased astrocyte glucose utilization; in such a case, partial blockade of glucose transport should have diminished the size of the dips.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Cytosolic NADH transients reflect increased neuronal glycolysis upon stimulation
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus there is bidirectional coupling between glucose and NADHCYT: the NADHCYT transients were diminished when glycolysis was inhibited, and glucose dips were diminished when NAD+ recycling was inhibited (by blocking lactate export).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Cytosolic NADH transients reflect increased neuronal glycolysis upon stimulation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This likely rapid depletion of pyruvate suggests that there is at least some mismatch between the rate of pyruvate production by glycolysis and the rate of pyruvate oxidation by mitochondria - in other words, that there is at least some net “aerobic glycolysis” of glucose to lactate in the neurons.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Transient aerobic glycolysis may provide a rapid first response to energy resupply, followed by the higher capacity response by oxidative phosphorylation
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Given that neuronal metabolic responses to stimulation do not rely on lactate import, it seems very likely that neurons turn instead to increased glucose metabolism for their increased energy needs.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Coordinated dips in neuronal [glucose] and increases in NADHCYT point to increased glycolysis after stimulation
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“as it has been previously demonstrated that anesthesia increases the apparent oxygen concentration of intact brain (Lyons et al., 2016).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > STAR★Methods > Method Details
What the sources say
- Not checked yetcites Lyons et al., 2016 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In fact, this mismatch between blood flow and oxygen consumption is the source of the BOLD signal that is commonly used to detect brain activation in functional imaging experiments (Kwong et al., 1992):”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Transient aerobic glycolysis may provide a rapid first response to energy resupply, followed by the higher capacity response by oxidative phosphorylation
What the sources say
- Not checked yetcites Kwong et al., 1992 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Even with this correction, the effect of some green signal from RCaMP1h still appears to produce some shift of the baseline lifetime values for Peredox, compared to those seen in the absence of RCaMP1h (Mongeon et al., 2016).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > STAR★Methods > Quantification and Statistical Analyses
What the sources say
- Not checked yetcites Mongeon et al., 2016 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and that instead glycolysis – the net conversion of glucose to lactate –becomes a substantial component of the transient response to activation.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Transient aerobic glycolysis may provide a rapid first response to energy resupply, followed by the higher capacity response by oxidative phosphorylation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Although in principle it is possible that expression of the Peredox sensor, an NADH binding protein, could buffer increases in free [NADH], we saw no evidence of this: the average change in sensor LT was uncorrelated with the level of sensor protein expression, judged from fluorescence intensity (Suppl. Fig. S2).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > STAR★Methods > Method Details
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“blood oxygenation level is somewhat paradoxically increased in activated regions, despite the increased metabolic demand.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Transient aerobic glycolysis may provide a rapid first response to energy resupply, followed by the higher capacity response by oxidative phosphorylation
What the sources say
- Not checked yetcites Kwong et al., 1992 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These observations support the idea that increased glucose consumption is not accompanied by an equivalent increase in mitochondrial pyruvate oxidation”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Transient aerobic glycolysis may provide a rapid first response to energy resupply, followed by the higher capacity response by oxidative phosphorylation
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and that during activation they are likely to be exporters of glycolytic lactate rather than consumers of lactate from astrocytes.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Transient aerobic glycolysis may provide a rapid first response to energy resupply, followed by the higher capacity response by oxidative phosphorylation
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The MCT inhibitor AR-C155858 was purchased from Tocris (Bristol, UK); it is highly specific to MCT1 and MCT2 (Ovens et al., 2010a)”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > STAR★Methods > Method Details
What the sources say
- Not checked yetcites Ovens et al., 2010a
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 18
- Probably not a substantial claim. 15
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The opposite was seen: blockade of the postsynaptic response (as judged from the disappearance of the postsynaptic Ca2+ transient, and the disappearance of the EPSP from an extracellular electrode; Fig 2A, B and Suppl. Fig. S3) was accompanied by disappearance of the NADHCYT transient (Fig 2B, C).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Astrocyte stimulation by glutamate is neither sufficient nor necessary for neuronal NADH transients
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Practically all of these responsive neurons exhibited an approximately 4–5 minute long elevation in NADHCYT (Figure 7A, B), while neighboring non-responsive neurons showed no significant change.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Similar neuronal cytosolic NADH transients occur in vivo with normal sensory stimulation
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Application of the MCT inhibitor AR-C155858 (at 50 μM rather than the 2 μM used for slice) effectively reduced the size of the lactate-induced increase (by 85.3% ± 6.3%, mean ± SEM, n=59 neurons in 6 animals; Fig. 7D). Nevertheless, neuronal NADHCYT transients induced by whisker stimulation were not diminished by the MCT inhibitor (Fig. 7E, F).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Similar neuronal cytosolic NADH transients occur in vivo with normal sensory stimulation
plaindirectn = 59- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observed small transient drops (dips) in neuronal intracellular [glucose] upon synaptic stimulation that had a very similar time course to the NADHCYT transients (Fig. 5A).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Cytosolic NADH transients reflect increased neuronal glycolysis upon stimulation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As expected, application of the LDH inhibitor reduced the NADHCYT response to direct application of exogenous lactate (by 78% ± 3% of the original response, mean ± SEM, n=54 neurons; Fig. 3E).”
- Also stated in: § Lactate import does not contribute to neuronal NADHCYT transients · plain
“Instead, the stimulation-induced NADHCYT responses were larger (by 37% ± 5%; n=54 neurons; Fig. 3F), as expected for production of NADH within the neuron when LDH-dependent recycling to NAD+ is inhibited.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Lactate import does not contribute to neuronal NADHCYT transients
plaindirectn = 54- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The LDH inhibitor GSK-2837808A specifically inhibits lactate dehydrogenase.
- Also stated in: § Lactate import does not contribute to neuronal NADHCYT transients · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When we deliberately reduced glucose transport rate chronically, by partial inhibition with cytochalasin B, the baseline [glucose]i was predictably lower, but the stimulation-induced dips in [glucose]i actually became larger (Fig 5A, B), consistent with our hypothesis.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Cytosolic NADH transients reflect increased neuronal glycolysis upon stimulation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In dentate granule neurons in a hippocampal slice, the typical increase in this ratio is substantial - approximately a 2-fold increase above the resting level. In neurons of barrel cortex observed in vivo, the typical increase is smaller (about a 33% increase over the resting level), but still substantial.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > The NADH biosensor reports metabolic transients specifically in neuronal cytosol
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“IAA treatment diminished the baseline (consistent with a contribution of glycolysis to the resting NADHCYT level), and upon return to the experimental temperature, the stimulation-induced NADHCYT transient was much smaller, despite a slightly larger Ca2+ transient in response to stimulation.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Cytosolic NADH transients reflect increased neuronal glycolysis upon stimulation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“It is generally agreed that the “resting” brain, under normal metabolic circumstances, consumes glucose and metabolizes it nearly completely to CO2 (Clarke and Sokoloff, 1994; Madsen et al., 1999).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > INTRODUCTION
What the sources say
- Not checked yetcites Clarke and Sokoloff, 1994
- Not checked yetcites Madsen et al., 1999 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Because our experiments were all done with optical signals from the cell bodies of neurons, we cannot exclude the possibility of ANLS activity at synaptic terminals”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Astrocyte-to-neuron lactate shuttling may occur at rest, but not during neuronal stimulation
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our results support the possibility of an ANLS that functions at rest but not during neuronal stimulation.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Astrocyte-to-neuron lactate shuttling may occur at rest, but not during neuronal stimulation
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The failure of MCT inhibitor to abolish the stimulation-induced transients in vivo supports the conclusion that such metabolic transients are endogenous to the neurons and do not rely on lactate import from the extracellular space or from astrocytes.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Similar neuronal cytosolic NADH transients occur in vivo with normal sensory stimulation
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The physiological coordination of both glycolysis and oxidative metabolism in response to neuronal activity may be choreographed by calcium influx, which, as shown in Figs. 1D and 7C, is tightly correlated to the cytosolic NADH transients.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Transient aerobic glycolysis may provide a rapid first response to energy resupply, followed by the higher capacity response by oxidative phosphorylation
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The fact that the transients are actually larger when the MCTs are inhibited may indicate that neurons normally export lactate when their metabolism is activated by stimulation, as discussed below.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Lactate import does not contribute to neuronal NADHCYT transients
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“NADHCYT can rise in response to either increased glycolysis (which converts NAD+ to NADH at the GAPDH step), to increased conversion of lactate to pyruvate, or to decreased activity of mitochondrial NADH shuttles.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > RESULTS > Stimulation produces transient increases of cytosolic NADH:NAD+ in individual neurons
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Wild-type C57BL/6NCrl mice of both genders were bred in house and used in all acute brain slice and in vivo experiments, and mice were randomly allocated to experimental groups.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > STAR★Methods > Experimental Models and Subject Details
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Similarly, RCaMP1h expression alone led to some signal in the green optical channel, probably due to an immature fluorophore, in direct experiments approximately 4.4% of the red fluorescence intensity, and having a lifetime of ~0.71 ns; these values were used to correct the baseline in dual expression experiments.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > STAR★Methods > Quantification and Statistical Analyses
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“When imaging from the same cortical region on multiple days, previously imaged neurons were re-identified using the pattern of the surface vasculature as guidance, and then an adjacent volume was selected to ensure that all neurons in the sample were unique.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > STAR★Methods > Method Details
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Like muscle, the brain has no doubt evolved to meet the large instant-to-instant changes in energy demands with a choreographed regulation of the core metabolic pathways, to ensure not only brain cell health but organismal survival.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Transient aerobic glycolysis may provide a rapid first response to energy resupply, followed by the higher capacity response by oxidative phosphorylation
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Viral expression of Peredox and RCaMP1h permitted recording from different neurons in the same mice on different days (Andermann et al., 2010; O’Connor et al., 2010).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > STAR★Methods > Method Details
What the sources say
- Not checked yetcites Andermann et al., 2010
- Not checked yetcites O’Connor et al., 2010
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“PET studies also show that blood flow and glucose consumption are dramatically increased by brain activation, but oxygen consumption barely increases (Fox and Raichle, 1986; Fox et al., 1988).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Transient aerobic glycolysis may provide a rapid first response to energy resupply, followed by the higher capacity response by oxidative phosphorylation
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Most likely the changes in free [NADH] are already buffered by high levels of cytosolic dehydrogenases that bind NADH (Zhang et al., 2002), and the additional expression of sensor makes only a negligible change in the buffering capacity.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > STAR★Methods > Method Details
What the sources say
- Not checked yetcites Zhang et al., 2002
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For this reason, we mostly measured the net lifetime change for the transients, relative to baseline (ΔLT).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > STAR★Methods > Quantification and Statistical Analyses
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“However, it is known that in the evolution of skeletal muscle, the muscle fibers with the most dynamic energy requirements -- the fast-twitch fibers -- tend to rely on glycolysis for prompt energy production (Crow and Kushmerick, 1982; Spriet, 1989).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Transient aerobic glycolysis may provide a rapid first response to energy resupply, followed by the higher capacity response by oxidative phosphorylation
What the sources say
- Not checked yetcites Crow and Kushmerick, 1982
- Not checked yetcites Spriet, 1989
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“unlike the commonly used MCT inhibitor α-cyano-4-hydroxycinnamate (4-CIN), which blocks mitochondrial pyruvate uptake with higher affinity than it blocks MCTs (Halestrap and Denton, 1974).”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > STAR★Methods > Method Details
What the sources say
- Not checked yetcites Halestrap and Denton, 1974
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Bleedthrough of green Peredox fluorescence into the red RCaMP optical channel was corrected using the ratio of measured red to green fluorescence observed when only Peredox was expressed (Suppl. Fig. S2), approximately 6.0%.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > STAR★Methods > Quantification and Statistical Analyses
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“of “catch-up” oxidation by many neighboring brain cells (and by the stimulated neurons themselves) as well as some net lactate excretion from the brain (Dienel, 2012; Glenn et al., 2015), particularly when activation is strong and synchronous, as in epilepsy (Collins et al., 1970; During et al., 1994)”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > DISCUSSION > Transient aerobic glycolysis may provide a rapid first response to energy resupply, followed by the higher capacity response by oxidative phosphorylation
What the sources say
- Not checked yetcites Dienel, 2012 source
- Not checked yetcites Glenn et al., 2015
- Not checked yetcites Collins et al., 1970
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Likewise, green glucose sensor fluorescence produced a bleedthrough of ~5.9% to the red channel.”
§ Neuronal stimulation triggers neuronal glycolysis and not lactate uptake > STAR★Methods > Quantification and Statistical Analyses
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
The increased energy demand during brain excitation occurs mainly within neurons.
“although the increased energy demand occurs mainly within neurons, some have suggested this glycolysis occurs mainly in astrocytes”
The paper relies on this without support.
The Peredox biosensor is expressed in the cytosol and not targeted to mitochondria.
“The biosensor is expressed in cytosol and not targeted to mitochondria; it therefore reports cytosolic NADH: NAD+ ratio.”
The paper relies on this without support.
NADH does not pass through mitochondrial membranes.
“The NADHCYT transients reported by Peredox are in principle compartmentally separated from the changes in mitochondrial NADH, and NADH does not pass through the mitochondrial membranes.”
The paper relies on this without support.
The LDH inhibitor GSK-2837808A specifically inhibits lactate dehydrogenase.
“the neuronal NADHCYT transients were elevated rather than abolished upon inhibition of lactate dehydrogenase by the high-affinity inhibitor GSK-2837808A (2 μM; Fig. 3D, F).”
The paper relies on this without support.
Both glycolysis and oxidative metabolism are elevated after stimulation.
“Despite the fact that both glycolysis and oxidative metabolism are elevated after stimulation”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“but previously published data strongly indicate that the increase in lactate and glutamate levels is the consequence of the surge in glycolysis and the ensuing increase of cytosolic NADH:NAD+ ratio taking place during neuronal activation (Díaz-García et al., 2017).”
From Perception is associated with the brain’s metabolic response to sensory stimulation (2022) · cites this paper as Díaz-García et al., 2017
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“This is consistent with a recent report that astrocyte-derived lactate is not required for the bioenergetic response to stimulation in neurons (Díaz-García et al., 2017).”
From ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism (2021) · cites this paper as Díaz-García et al., 2017
In the citing paper
“However, the use of pure lactate as an alternative fuel, rather than a redox-balanced mixture of lactate and pyruvate, abnormally elevates the low cytosolic NADH redox ratio in neurons (seen in vitro by Hung et al. [2011] and Mongeon et al. [2016] as well as in vivo by Díaz-García et al. [2017]); this decreases the rate of neuronal glycolysis in a way that would not represent the normal effect in”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Díaz-García et al., 2017
In the citing paper
“Inhibition of MCT in vivo in the cortical neurons of awake mice also blocks the NADHCYT response to exogenous lactate but not to sensory stimulation.”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Díaz-García et al., 2017
In the citing paper
“These blockers instead lead to enhancement of the NADHCYT transients, suggesting that neurons normally export lactate when stimulated.”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Díaz-García et al., 2017
In the citing paper
“With brief neuronal excitation in an acute hippocampal slice, NADHCYT rises rapidly and remains elevated for ∼2–3 min, reflecting a temporary imbalance favoring production of NADH over its recycling back to NAD+.”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Díaz-García et al., 2017
In the citing paper
“The NADHCYT transients decrease with inhibition of glycolysis but not of the MAS, indicating that increased neuronal glycolysis upon stimulation is the main cause of the NADHCYT transients.”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Díaz-García et al., 2017
In the citing paper
“Pharmacologic blockade of MCT or of LDH abolishes the elevation of NADHCYT in response to exogenous lactate but not in response to stimulation, which rules out a role of lactate import in producing the transient increases in neuronal NADHCYT.”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Díaz-García et al., 2017
In the citing paper
“In dentate granule neurons, MCT inhibition led to higher peaks of NADHCYT as well as smaller dips in glucose, suggesting that the elevated NADHCYT also exerted back pressure on glycolysis, presumably on the GAPDH equilibrium (Díaz-García et al., 2017).”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Díaz-García et al., 2017
Citations
Cites
Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation.
Kwong, K. K., Belliveau, J. W., Chesler, D. A., Goldberg, I. E., Weisskoff, R. M., Poncelet, B. P., Kennedy, D. N., Hoppel, B. E., Cohen, M. S., & Turner, R. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.12.5675 · Cited by 4,212 · cited 2×
“imaging experiments (Kwong et al., 1992): blood oxygenation level is somewhat paradoxically increased in activated regions, despite the increased metabolic demand.”
Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq
Zeisel, A., Muñoz-Manchado, A. B., Codeluppi, S., Lönnerberg, P., La Manno, G., Juréus, A., Marques, S., Munguba, H., He, L., Betsholtz, C., et al. (2015) · Science · doi:10.1126/science.aaa1934 · Cited by 3,124 · cited 1×
“…(Salway, 2004; in neurons, mainly the malate-aspartate shuttle [MAS], McKenna et al., 2006); unbiased proteomics and transcriptomics surveys of central neurons reveal that these are by far the dominant NADH dehydrogenase enzymes in the cytosol (Sharma et al., 2015; Zeisel et al., 2015; Figure S1).”
Pellerin, L., & Magistretti, P. J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.22.10625 · Cited by 2,927
Brain energy metabolism: focus on Astrocyte-neuron metabolic cooperation
Bélanger, M., Allaman, I., & Magistretti, P. J. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.016 · Cited by 2,313 · cited 2×
“…an ‘‘astrocyte-neuron lactate shuttle’’ (ANLS), which proposes that astrocytes are stimulated by neuronal glutamate release to convert more glucose to lactate, which is then Cell released by the astrocytes to serve as fuel for the neighboring neurons (Bélanger et al., 2011; Pellerin et al., 1998).”
Fox, P. T., & Raichle, M. E. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.4.1140 · Cited by 2,056 · cited 2×
“However, with brain activation, glucose consumption increases much more than oxygen consumption (Fox and Raichle, 1986; Fox et al., 1988).”
Williamson, D., Lund, P., & Krebs, H. (1967) · Biochemical Journal · doi:10.1042/bj1030514 · Cited by 1,871 · cited 2×
“This produced a large and prompt increase in NADHCYT, likely mediated by the rapid action of LDH, which converts NAD to NADH in parallel with the conversion of lactate to pyruvate (Williamson et al., 1967; Hung et al., 2011).”
Nonoxidative Glucose Consumption During Focal Physiologic Neural Activity
Fox, P. T., Raichle, M. E., Mintun, M. A., & Dence, C. (1988) · Science · doi:10.1126/science.3260686 · Cited by 1,796 · cited 2×
“However, with brain activation, glucose consumption increases much more than oxygen consumption (Fox and Raichle, 1986; Fox et al., 1988).”
ScanImage: Flexible software for operating laser scanning microscopes
Pologruto, T. A., Sabatini, B. L., & Svoboda, K. (2003) · BioMedical Engineering OnLine · doi:10.1186/1475-925x-2-13 · Cited by 1,300
Basic Neurochemistry???Molecular, Cellular, and Medical Aspects
Long, D. M. (2006) · Neurosurgery Quarterly · doi:10.1097/01.wnq.0000203279.82150.41 · Cited by 1,294
Sensitive red protein calcium indicators for imaging neural activity
Dana, H., Mohar, B., Sun, Y., Narayan, S., Gordus, A. G., Hasseman, J. P., Tsegaye, G., Holt, G. T., Hu, A., Walpita, D., et al. (2016) · eLife · doi:10.7554/elife.12727 · Cited by 1,052
Cited by
Sorted by citations
Lactate in the brain: from metabolic end-product to signalling molecule
Magistretti, P. J., & Allaman, I. (2018) · Nature Reviews Neuroscience · doi:10.1038/nrn.2018.19 · Cited by 1,298
Brain Glucose Metabolism: Integration of Energetics with Function
Dienel, G. A. (2018) · Physiological Reviews · doi:10.1152/physrev.00062.2017 · Cited by 911
Astrocyte-neuron metabolic cooperation shapes brain activity
Bonvento, G., & Bolaños, J. P. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.07.006 · Cited by 580
ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism
Qi, G., Mi, Y., Shi, X., Gu, H., Brinton, R. D., & Yin, F. (2021) · Cell Reports · doi:10.1016/j.celrep.2020.108572 · Cited by 379
Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism
Yellen, G. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201803152 · Cited by 371
“Fluorescent biosensor measurement of NADHCYT in neurons during excitation has helped to resolve the role of glycolysis and intercellular lactate transport in the acute metabolic response (Díaz-García et al., 2017).”
BackgroundSelf-citation
Metadata
- Authors
- Díaz-García, C. M., Mongeon, R., Lahmann, C., Koveal, D., Zucker, H., & Yellen, G.
- Affiliations
- Harvard University (US)
- Corresponding author
- Yellen, Gary
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 26
- Issue
- 2
- Pages
- 361-374.e4
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC5559896
- OpenAlex
- W2739924689
- Semantic Scholar
- a96cd5dd74379072ec837b55007abc76f4f54521
- Cited by
- 466
- References
- 71
- Citations by year
- 2026: 39 · 2025: 62 · 2024: 50 · 2023: 52 · 2022: 51 · 2021: 62 · 2020: 60 · 2019: 40 · 2018: 42 · 2017: 7
- FWCI
- 19.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R01 NS055031, DP1 EB016985, F32 NS080455, F32 NS093784, F32 NS100331)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- lactate utilization, brain energy metabolism, neurostimulation, astrocytes, glutamate release, glucose utilization, oxidative metabolism, hippocampal slices, brain energy demand
- MeSH terms
- Animals, Glycolysis, Hippocampus, Male, Neurons, Lactic Acid, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
