Cited by 74Neuroscience and Neuropharmacology ResearchMitochondrial Function and PathologyCellular transport and secretion

Differential presynaptic ATP supply for basal and high-demand transmission

Open access
Sobieski, Courtney, Fitzpatrick, Michael J., Mennerick, Steven J.·2017·The Journal of Neuroscience

Abstract

The relative contributions of glycolysis and oxidative phosphorylation to neuronal presynaptic energy demands are unclear. In rat hippocampal neurons, ATP production by either glycolysis or oxidative phosphorylation alone sustained basal evoked synaptic transmission for up to 20 min. However, combined inhibition of both ATP sources abolished evoked transmission. Neither action potential propagation failure nor depressed Ca 2+ influx explained loss of evoked synaptic transmission. Rather, inhibition of ATP synthesis caused massive spontaneous vesicle exocytosis, followed by arrested endocytosis, accounting for the disappearance of evoked postsynaptic currents. In contrast to its weak effects on basal transmission, inhibition of oxidative phosphorylation alone depressed recovery from vesicle depletion. Local astrocytic lactate shuttling was not required. Instead, either ambient monocarboxylates or neuronal glycolysis was sufficient to supply requisite substrate. In summary, basal transmission can be sustained by glycolysis, but strong presynaptic demands are met preferentially by oxidative phosphorylation, which can be maintained by bulk but not local monocarboxylates or by neuronal glycolysis. SIGNIFICANCE STATEMENT Neuronal energy levels are critical for proper CNS function, but the relative roles for the two main sources of ATP production, glycolysis and oxidative phosphorylation, in fueling presynaptic function in unclear. Either glycolysis or oxidative phosphorylation can fuel low-frequency synaptic function and inhibiting both underlies loss of synaptic transmission via massive vesicle release and subsequent failure to endocytose lost vesicles. Oxidative phosphorylation, fueled by either glycolysis or endogenously released monocarboxylates, can fuel more metabolically demanding tasks such as vesicle recovery after depletion. Our work demonstrates the flexible nature of fueling presynaptic function to maintain synaptic function.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1523/jneurosci.2712-16.2017

Cites

56 of 56 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Sobieski, C., Fitzpatrick, M. J., & Mennerick, S. J.
Affiliations
Washington University in St. Louis (US)
Venue
The Journal of Neuroscience
Published
2017-01-16
Volume
37
Issue
7
Pages
1888-1899
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2575996993
Cited by
74
References
56
Citations by year
2026: 8 · 2025: 4 · 2024: 10 · 2023: 13 · 2022: 5 · 2021: 12 · 2020: 5 · 2019: 5 · 2018: 9 · 2017: 3
FWCI
2.95
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (F31MH106198, R21MH099658, R01MH078823, R21MH104506)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
glycolysis, oxidative phosphorylation, synaptic transmission, vesicle exocytosis, endocytosis, hippocampal neurons, neuronal energy metabolism
MeSH terms
Action Potentials, Adenosine Triphosphate, Animals, Animals, Newborn, Astrocytes, Cells, Cultured, Endocytosis, Enzyme Inhibitors, Glycolysis, Hippocampus, Synaptic Transmission, Neurons, Phosphorylation, Potassium Chloride, Synaptic Vesicles, Rats, Sprague-Dawley, Presynaptic Terminals, Neurotransmitter Agents, Patch-Clamp Techniques, Rats, Synaptic Potentials

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.

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