Cited by 42Neuroscience and Neuropharmacology ResearchIon channel regulation and functionCellular transport and secretion

Rapid Ca 2+ channel accumulation contributes to cAMP-mediated increase in transmission at hippocampal mossy fiber synapses

Open access
Fukaya, Ryota, Maglione, Marta, Sigrist, Stephan J., Sakaba, Takeshi·2021·Proceedings of the National Academy of Sciences

Abstract

Significance: Despite the importance of the activation of the cAMP/PKA signaling pathway for presynaptic modulation, its cellular and molecular mechanisms remain unclear. In this study, we tackled this issue at hippocampal mossy fiber-CA3 synapses by combining paired electrophysiological recordings, Ca 2+ uncaging, total internal reflection fluorescence (TIRF) microscopy for direct measurements of presynaptic active zone Ca 2+ influx, and superresolution time-gated STED microscopy for visualization of Ca 2+ channel clusters within active zones. Our results suggest that Ca 2+ channels near release sites might accumulate upon activation of the cAMP/PKA pathway in the time scale of only several minutes. Our findings may thus change the focus from release machinery to Ca 2+ channel clusters and their dynamics as a cell biological mechanism of cAMP-dependent synaptic modulation.

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 · 10.1073/pnas.2016754118

Cites

69 of 69 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?

  • Neither an increase in the number of Ca2+ channels nor a functional modulation of Ca2+ channels accounts for the Pr change upon induction of chemical potentiation.

    “However, a previous study and our results show that neither of them accounts for Pr change upon the induction of chemical potentiation (Fig 4D and 4E) [47].”

    From Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons (2024) · cites this paper as [47]

    The Discussion section, “Increased Ca2+ Concentration at Mossy Fiber Release Sites under cAMP,” favors Ca2+ channel accumulation at release sites as a mechanism of potentiation and says an increase in channel numbers is consistent with the observed cluster expansion. That contradicts the claim that an increase in channel number does not account for the change in release probability. The Results report that forskolin did not amplify the overall inward Ca2+ current, but that does not negate the paper’s proposed local channel-accumulation mechanism. (LLM, conf=0.90)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured
  • Previous studies reported a lack of change in coupling distance between CaV2.1 and Munc13-1.

    “However, previous studies reported a lack of change in coupling distance between CaV2.1 and Munc13-1 [46,47].”

    From Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons (2024) · cites this paper as [47]

    The Results (gSTED microscopy section) report similar measured peak-to-peak distances between CaV2.1 and Munc13-1 clusters under control and forskolin conditions. But the authors explicitly caution that these measurements cannot exclude subtle changes in physical coupling distance, so an unqualified lack of change in coupling distance overstates the finding. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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
Fukaya, R., Maglione, M., Sigrist, S. J., & Sakaba, T.
Affiliations
  • Doshisha University (JP)
  • NeuroCure Cluster of Excellence (DE)
Corresponding author
  • Fukaya, Ryota
  • Maglione, Marta
  • Sigrist, Stephan J.
  • Sakaba, Takeshi
Venue
Proceedings of the National Academy of Sciences
Published
2021-02-23
Volume
118
Issue
9
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W3131482140
Cited by
42
References
69
Citations by year
2026: 4 · 2025: 6 · 2024: 10 · 2023: 9 · 2022: 9 · 2021: 4
FWCI
3.69
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Japan Society for the Promotion of Science (18H02530, 20K15905, core-to-core program A)
  • MEXT | Japan Society for the Promotion of Science (19H04760, 20KK0171)
  • Deutsche Forschungsgemeinschaft (FOR2750, SFB1315)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
cAMP/PKA signaling, presynaptic modulation, mossy fiber-CA3 synapses, hippocampus, active zone, calcium influx, synaptic transmission, calcium uncaging, STED microscopy
MeSH terms
Cyclic AMP, Calcium, Microscopy, Fluorescence, Synaptic Transmission, Neuronal Plasticity, Calcium Channels, Patch-Clamp Techniques, Mossy Fibers, Hippocampal

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