Evidence map›Paper›PMID 40916622›Full record

ArticleJournal of neurochemistry2025

Presynaptic ATP Decreases During Physiological-Like Activity in Neurons Tuned for High-Frequency Transmission.

Isabelle Straub, Lukas Kunstmann, Felipe Baeza-Lehnert, Saad Chowdhry, Robert B Renden, Gerardo Gonzalez-Aragón, Bernhard Groschup, Thomas Hofmann, Saša Jovanović, Mandy Sonntag and 6 more

Abstract read
In one paragraph

Article in Journal of neurochemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Inorganic phosphate and the rapid mobilization of metabolic energy in neurons.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Isabelle StraubCarl-Ludwig-Institute of Physiology, Faculty of Medicine, Leipzig University, Leipzig, Germany.
Lukas KunstmannCarl-Ludwig-Institute of Physiology, Faculty of Medicine, Leipzig University, Leipzig, Germany.
Felipe Baeza-LehnertCarl-Ludwig-Institute of Physiology, Faculty of Medicine, Leipzig University, Leipzig, Germany.
Saad ChowdhryDepartment of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, Nevada, USA.
Robert B RendenDepartment of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, Nevada, USA.
Gerardo Gonzalez-AragónCarl-Ludwig-Institute of Physiology, Faculty of Medicine, Leipzig University, Leipzig, Germany.
Bernhard GroschupCarl-Ludwig-Institute of Physiology, Faculty of Medicine, Leipzig University, Leipzig, Germany.
Thomas HofmannBasislager Coworking Leipzig, Leipzig, Sachsen, Germany.
Saša JovanovićInstitute of Biology, Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig, Leipzig, Germany.
Mandy SonntagMedical Faculty, Medizinisch-Experimentelles Zentrum, Leipzig University, Leipzig, Germany.
Daniel GitlerDepartment of Physiology and Cell Biology, Faculty of Health Sciences and School of Brain Sciences and Cognition, Ben-Gurion University of the Negev, Beer Sheva, Israel.ORCID https://orcid.org/0000-0001-9544-3610
Michael SchaeferRudolf Boehm Institute of Pharmacology and Toxicology, Faculty of Medicine, Leipzig University, Leipzig, Germany.
Jens EilersCarl-Ludwig-Institute of Physiology, Faculty of Medicine, Leipzig University, Leipzig, Germany.
L Felipe BarrosCentro de Estudios Científicos (CECs), Valdivia, Chile.ORCID https://orcid.org/0000-0002-6623-4833
Johannes HirrlingerCarl-Ludwig-Institute of Physiology, Faculty of Medicine, Leipzig University, Leipzig, Germany.ORCID https://orcid.org/0000-0002-6327-0089
Stefan HallermannCarl-Ludwig-Institute of Physiology, Faculty of Medicine, Leipzig University, Leipzig, Germany.ORCID https://orcid.org/0000-0001-9376-7048

Funding

Dynamin-Related Protein 1 and Mitochondrial Fission Adapters Regulate Presynaptic FunctionR01NS119980 · NINDS · UNIVERSITY OF NEVADA RENO · PI ROBERT B RENDEN · 2023 to 2026
$1.8M
Activity-dependent energy homeostasis at the presynaptic terminalR01NS117686 · NINDS · UNIVERSITY OF NEVADA RENO · PI RENDEN, ROBERT B · 2020 to 2022
$1.6M
Deutsche Forschungsgemeinschaft HA6386/8-1European Molecular Biology Organization ALTF 382-2021European Research Council CoG 865634NINDS NIH HHS R01 NS117686NINDS NIH HHS R01 NS119980
6 · The paper itself

Abstract

Recent evidence indicates that the concentration of ATP remains stable during neuronal activity due to activity-dependent ATP production. However, the mechanisms of activity-dependent ATP production remain controversial. To stabilize the ATP concentration, feedforward mechanisms, which may rely on calcium or the sodium-potassium pump, do not require changes in the ATP and ADP concentrations. On the other hand, feedback mechanisms could be triggered by changes in the concentration of the adenine nucleotides. To test the possibility of feedback mechanisms, we quantified the ATP concentration in presynaptic terminals during synaptic activity in acute brain slices from mice stably expressing a genetically encoded ATP sensor. We first focused on the cerebellar mossy fiber bouton (cMFB) as a large presynaptic terminal that is specialized for high-frequency synaptic transmission. At physiological temperature and metabolite concentrations, the resting ATP concentration was in the range of approximately 2.5-2.7 mM. During strong, presumably non-physiological activity, the ATP concentration decreased within a few seconds. Experiments with blockade of ATP production indicated that ATP production increased ~10-fold during neuronal activity. Weaker stimulation resembling physiological activity at this synapse caused a decrease in ATP concentration by ~150 μM. We found similar results with in vivo-recorded spike sequences at the calyx of Held, another central glutamatergic synapse tuned for high-frequency synaptic activity. At conventional small synapses of cultured hippocampal neurons, weak stimulations also caused a decrease in ATP concentrations. Finally, quantitative modeling indicated that a pure ADP-based feedback mechanism can explain the activity-dependent ATP production when assuming a three-times higher maximal rate of ATP production compared to our measured rate of ATP production during high-frequency transmission. Our data reveal ATP reduction in presynaptic terminals during physiological-like activity, provide quantitative constraints on feedback mechanisms, and suggest that the ATP concentration can decrease during signaling, at least in some neuronal compartments of our brain.

Indexed as

Adenosine TriphosphateNeuronsPresynaptic TerminalsSynaptic TransmissionAnimalsMaleMiceMice, Inbred C57BLMice, TransgenicAdenosine TriphosphateATPneuronal metabolismpresynaptic function

Identifiers

PMID40916622
PMCPMC12415541

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.