The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Synaptic weight set by Munc13-1 supramolecular assemblies
Abstract
The weight of synaptic connections, which is controlled not only postsynaptically but also presynaptically, is a key determinant in neuronal network dynamics. The mechanisms controlling synaptic weight, especially on the presynaptic side, remain elusive. Using single-synapse imaging of the neurotransmitter glutamate combined with super-resolution imaging of presynaptic proteins, we identify a presynaptic mechanism for setting weight in central glutamatergic synapses. In the presynaptic terminal, Munc13-1 molecules form multiple and discrete supramolecular self-assemblies that serve as independent vesicular release sites by recruiting syntaxin-1, a soluble N-ethylmaleimide-sensitive-factor attachment receptor (SNARE) protein essential for synaptic vesicle exocytosis. The multiplicity of these Munc13-1 assemblies affords multiple stable states conferring presynaptic weight, potentially encoding several bits of information at individual synapses. Supramolecular assembling enables a stable synaptic weight, which confers robustness of synaptic computation on neuronal circuits and may be a general mechanism by which biological processes operate despite the presence of molecular noise.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“Furthermore, we discovered that forskolin slightly reduced the distance between CaV2.1 (P/Q-type) Ca2+ channels and Munc13-1, an essential vesicle priming protein and putative marker of primed vesicles [14,40–45].”
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 [45]
In the citing paper
“and Munc13-1/2, putative markers of primed vesicles [14,42–45,60,61].”
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 [45]
Citations
Cites
The chemical basis of morphogenesis
Turing, A. M. (1952) · Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences · doi:10.1098/rstb.1952.0012 · Cited by 11,733
Whitesides, G. M., & Grzybowski, B. A. (2002) · Science · doi:10.1126/science.1070821 · Cited by 7,550
Short-Term Synaptic Plasticity
Zucker, R. S., & Regehr, W. G. (2002) · Annual Review of Physiology · doi:10.1146/annurev.physiol.64.092501.114547 · Cited by 5,068
Malenka, R. C., & Bear, M. F. (2004) · Neuron · doi:10.1016/j.neuron.2004.09.012 · Cited by 3,968
Three-Dimensional Super-Resolution Imaging by Stochastic Optical Reconstruction Microscopy
Huang, B., Wang, W.-Q., Bates, M., & Zhuang, X. (2008) · Science · doi:10.1126/science.1153529 · Cited by 2,830
Quantal components of the end‐plate potential
del Castillo, J., & Katz, B. (1954) · The Journal of Physiology · doi:10.1113/jphysiol.1954.sp005129 · Cited by 2,201
Subdiffraction‐Resolution Fluorescence Imaging with Conventional Fluorescent Probes
Heilemann, M., van de Linde, S., Schüttpelz, M., Kasper, R. T., Seefeldt, B., Mukherjee, A., Tinnefeld, P., & Sauer, M. (2008) · Angewandte Chemie International Edition · doi:10.1002/anie.200802376 · Cited by 1,870
Statistical Analysis and Modelling of Spatial Point Patterns
Illian, J., Penttinen, A., Stoyan, H., & Stoyan, D. (2007) · Wiley eBooks · doi:10.1002/9780470725160 · Cited by 1,852
Tsodyks, M. V., & Markram, H. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.2.719 · Cited by 1,634
Multicolor Super-Resolution Imaging with Photo-Switchable Fluorescent Probes
Bates, M., Huang, B., Dempsey, G. T., & Zhuang, X. (2007) · Science · doi:10.1126/science.1146598 · Cited by 1,507
Evaluation of fluorophores for optimal performance in localization-based super-resolution imaging
Dempsey, G. T., Vaughan, J. C., Chen, K. H., Bates, M., & Zhuang, X. (2011) · Nature Methods · doi:10.1038/nmeth.1768 · Cited by 1,405
Heterogeneity of release probability, facilitation, and depletion at central synapses
Dobrunz, L. E., & Stevens, C. F. (1997) · Neuron · doi:10.1016/s0896-6273(00)80338-4 · Cited by 1,183
The release of neural transmitter substances
Katz, B. (1969) · Medical Entomology and Zoology · Cited by 1,126
Direct stochastic optical reconstruction microscopy with standard fluorescent probes
van de Linde, S., Löschberger, A., Klein, T., Heidbreder, M., Wolter, S., Heilemann, M., & Sauer, M. (2011) · Nature Protocols · doi:10.1038/nprot.2011.336 · Cited by 1,104
Definition of the readily releasable pool of vesicles at hippocampal synapses.
Rosenmund, C., & Stevens, C. (1996) · Neuron · doi:10.1016/s0896-6273(00)80146-4 · Cited by 1,084
Südhof, T. C. (2012) · Neuron · doi:10.1016/j.neuron.2012.06.012 · Cited by 1,062
Molecular machines governing exocytosis of synaptic vesicles
Jahn, R., & Fasshauer, D. (2012) · Nature · doi:10.1038/nature11320 · Cited by 1,004
AMPARs and Synaptic Plasticity: The Last 25 Years
Huganir, R. L., & Nicoll, R. A. (2013) · Neuron · doi:10.1016/j.neuron.2013.10.025 · Cited by 968
Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles
Augustin, I., Rosenmund, C., Südhof, T. C., & Brose, N. (1999) · Nature · doi:10.1038/22768 · Cited by 787
Superresolution Imaging of Chemical Synapses in the Brain
Dani, A., Huang, B., Bergan, J. F., Dulac, C. G., & Zhuang, X. (2010) · Neuron · doi:10.1016/j.neuron.2010.11.021 · Cited by 748
The release of neural transmitter substances
Hubbard, J. I. (1970) · Electroencephalography and Clinical Neurophysiology · doi:10.1016/0013-4694(70)90283-x · Cited by 718
Probing protein heterogeneity in the plasma membrane using PALM and pair correlation analysis
Sengupta, P., Jovanović‐Talisman, T., Skoko, D., Renz, M., Veatch, S. L., & Lippincott‐Schwartz, J. (2011) · Nature Methods · doi:10.1038/nmeth.1704 · Cited by 588
Self-organization in cell biology: a brief history
Karsenti, E. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2357 · Cited by 575
Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming
Betz, A., Thakur, P., Junge, H. J., Ashery, U., Rhee, J.-S., Scheuss, V., Rosenmund, C., Rettig, J., & Brose, N. (2001) · Neuron · doi:10.1016/s0896-6273(01)00272-0 · Cited by 425
Munc13-1 is a presynaptic phorbol ester receptor that enhances neurotransmitter release
Betz, A., Ashery, U., Rickmann, M., Augustin, I., Neher, E., Südhof, T. C., Rettig, J., & Brose, N. (1998) · Neuron · doi:10.1016/s0896-6273(00)80520-6 · Cited by 425
The Morphological and Molecular Nature of Synaptic Vesicle Priming at Presynaptic Active Zones
Imig, C., Min, S.-W., Krinner, S., Arancillo, M., Rosenmund, C., Südhof, T. C., Rhee, J., Brose, N., & Cooper, B. H. (2014) · Neuron · doi:10.1016/j.neuron.2014.10.009 · Cited by 389
Munc13 mediates the transition from the closed syntaxin–Munc18 complex to the SNARE complex
Ma, C., Li, W., Xu, Y., & Rizo, J. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2047 · Cited by 363
Diversification of synaptic strength: presynaptic elements
Atwood, H. L., & Karunanithi, S. (2002) · Nature reviews. Neuroscience · doi:10.1038/nrn876 · Cited by 346
Facilitation at single synapses probed with optical quantal analysis
Oertner, T. G., Sabatini, B. L., Nimchinsky, E. A., & Svoboda, K. (2002) · Nature Neuroscience · doi:10.1038/nn867 · Cited by 320
Veatch, S. L., Machta, B. B., Shelby, S. A., Chiang, E. N., Holowka, D. A., & Baird, B. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031457 · Cited by 290
Silver, R., Momiyama, A., & Cull-Candy, S. (1998) · Journal of Physiology · doi:10.1111/j.1469-7793.1998.881bj.x · Cited by 279
High-Probability Uniquantal Transmission at Excitatory Synapses in Barrel Cortex
Silver, R. A., Lübke, J. H. R., Sakmann, B. J., & Feldmeyer, D. (2003) · Science · doi:10.1126/science.1087160 · Cited by 247
Fast vesicle reloading and a large pool sustain high bandwidth transmission at a central synapse
Saviane, C., & Silver, R. A. (2006) · Nature · doi:10.1038/nature04509 · Cited by 241
Neher, E. (2015) · Neuron · doi:10.1016/j.neuron.2015.08.038 · Cited by 236
Unveiling synaptic plasticity: a new graphical and analytical approach
Clements, J. D., & Silver, R. A. (2000) · Trends in Neurosciences · doi:10.1016/s0166-2236(99)01520-9 · Cited by 224
Active zone scaffolds differentially accumulate Unc13 isoforms to tune Ca2+ channel–vesicle coupling
Böhme, M. A., Beis, C., Reddy‐Alla, S., Reynolds, E., Mampell, M. M., Grasskamp, A. T., Lützkendorf, J., Bergeron, D. D., Driller, J. H., Babikir, H. A., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4364 · Cited by 219
Neher, E. (2010) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2010.00144 · Cited by 209
Open Syntaxin Docks Synaptic Vesicles
Hammarlund, M., Palfreyman, M. T., Watanabe, S., Olsen, S. R., & Jørgensen, E. M. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050198 · Cited by 201
Silver, R. A. (2003) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2003.09.030 · Cited by 168
Baddeley, D., Crossman, D. J., Roßberger, S., Cheyne, J. E., Montgomery, J. M., Jayasinghe, I., Cremer, C. G., Cannell, M. B., & Soeller, C. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020645 · Cited by 167
Actin- and Myosin-Dependent Vesicle Loading of Presynaptic Docking Sites Prior to Exocytosis
Miki, T., Malagón, G., Pulido, C., Llano, I., Neher, E., & Marty, A. (2016) · Neuron · doi:10.1016/j.neuron.2016.07.033 · Cited by 164
Enzymatic production of RNAi libraries from cDNAs
Shirane, D., Sugao, K., Namiki, S., Tanabe, M., Iino, M., & Hirose, K. (2004) · Nature Genetics · doi:10.1038/ng1290 · Cited by 160
Self-citationA common molecular basis for membrane docking and functional priming of synaptic vesicles
Siksou, L., Varoqueaux, F., Pascual, O., Triller, A., Brose, N., & Marty, S. (2009) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2009.06811.x · Cited by 160
Role of the synaptic ribbon in transmitting the cone light response
Jackman, S. L., Choi, S., Thoreson, W. B., Rábl, K., Bartoletti, T. M., & Krämer, R. (2009) · Nature Neuroscience · doi:10.1038/nn.2267 · Cited by 160
Neurotransmitter Release at Central Synapses
Stevens, C. F. (2003) · Neuron · doi:10.1016/s0896-6273(03)00643-3 · Cited by 158
Multivesicular Release at Schaffer Collateral–CA1 Hippocampal Synapses
Christie, J. M., & Jahr, C. E. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4307-05.2006 · Cited by 144
Korn, H., Triller, A., Mallet, A., & Faber, D. S. (1981) · Science · doi:10.1126/science.6266015 · Cited by 141
Spatial organization of intracellular communication: insights from imaging
Dehmelt, L., & Bastiaens, P. I. H. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2903 · Cited by 136
Binding of Clostridium botulinum Type C and D Neurotoxins to Ganglioside and Phospholipid
Tsukamoto, K., Kohda, T., Mukamoto, M., Takeuchi, K., Ihara, H., Saito, M., & Kozaki, S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m507596200 · Cited by 129
Andrews-Zwilling, Y. S., Kawabe, H., Reim, K., Varoqueaux, F., & Brose, N. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601421200 · Cited by 105
Quantal Size Is Independent of the Release Probability at Hippocampal Excitatory Synapses
Biró, Á. A., Holderith, N. B., & Nusser, Z. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3688-04.2005 · Cited by 102
Wang, X., Hu, B., Zieba, A., Neumann, N. G., Kasper-Sonnenberg, M., Honsbein, A., Hultqvist, G., Conze, T., Witt, W., Limbach, C., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.1255-09.2009 · Cited by 96
der Kloot, W. V. (1988) · The Journal of Physiology · doi:10.1113/jphysiol.1988.sp017224 · Cited by 94
SIMPLE STOCHASTIC MODELS FOR THE RELEASE OF QUANTA OF TRANSMITTER FROM A NERVE TERMINAL
Vere‐Jones, D. (1966) · Australian Journal of Statistics · doi:10.1111/j.1467-842x.1966.tb00164.x · Cited by 92
Limbach, C., Laue, M. M., Wang, X., Hu, B., Thiede, N., Hultqvist, G., & Kilimann, M. W. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1101707108 · Cited by 92
SNARE Protein Recycling by αSNAP and βSNAP Supports Synaptic Vesicle Priming
Burgalossi, A., Jung, S., Meyer, G., Jockusch, W. J., Jahn, O., Taschenberger, H., O'Connor, V. M., Nishiki, T., Takahashi, M., Brose, N., et al. (2010) · Neuron · doi:10.1016/j.neuron.2010.09.019 · Cited by 89
Ariel, P., Hoppa, M. B., & Ryan, T. A. (2013) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2012.00009 · Cited by 66
Multiquantal release underlies the distribution of synaptic efficacies in the neocortex
Loebel, A. (2009) · Frontiers in Computational Neuroscience · doi:10.3389/neuro.10.027.2009 · Cited by 54
Formation and Stability of Synaptic Receptor Domains
Haselwandter, C. A., Calamai, M., Mehran Kardar, A., Triller, A., & da Silveira, R. A. (2011) · Physical Review Letters · doi:10.1103/physrevlett.106.238104 · Cited by 40
Takikawa, K., Asanuma, D., Namiki, S., Sakamoto, H., Ariyoshi, T., Kimpara, N., & Hirose, K. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201407181 · Cited by 32
Self-citationHuang, C., Bao, J., & Sakaba, T. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2381-10.2010 · Cited by 27
Research works printed but not linked: 1
- Cowan, W.M., Südhof, T.C. & Stevens, C.F. Synapses (Johns Hopkins Univ. Press, Baltimore, 2001).
Cited by
Sorted by citations
Presynaptic calcium channels: specialized control of synaptic neurotransmitter release
DOLPHIN, A. C., & Lee, A. (2020) · Nature reviews. Neuroscience · doi:10.1038/s41583-020-0278-2 · Cited by 291
New insights regarding SNARE proteins in autophagosome-lysosome fusion
Tian, X., Teng, J., & Chen, J. (2020) · Autophagy · doi:10.1080/15548627.2020.1823124 · Cited by 264
Molecular Mechanisms Underlying Neurotransmitter Release
Rizo, J. (2022) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-111821-104732 · Cited by 244
Sensory Processing at Ribbon Synapses in the Retina and the Cochlea
Moser, T., Grabner, C. P., & Schmitz, F. (2019) · Physiological Reviews · doi:10.1152/physrev.00026.2018 · Cited by 215
Mechanism of neurotransmitter release coming into focus
Rizo, J. (2018) · Protein Science · doi:10.1002/pro.3445 · Cited by 210
Metadata
- Authors
- Sakamoto, H., Ariyoshi, T., Kimpara, N., Sugao, K., Taiko, I., Takikawa, K., Asanuma, D., Namiki, S., & Hirose, K.
- Affiliations
- The University of Tokyo (JP)
- Corresponding author
- Hirose, Kenzo
- Venue
- Nature Neuroscience
- Published
- 2017-12-11
- Volume
- 21
- Issue
- 1
- Pages
- 41-49
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2772190072
- Cited by
- 235
- References
- 61
- Citations by year
- 2026: 21 · 2025: 27 · 2024: 33 · 2023: 26 · 2022: 34 · 2021: 32 · 2020: 31 · 2019: 18 · 2018: 11 · 2017: 2
- FWCI
- 8.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (17K08584, 17H04029)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- synaptic weights, Munc13-1, supramolecular self-assembly, presynaptic terminals, glutamate release, syntaxin-1, SNARE proteins, synaptic vesicle exocytosis, glutamatergic synapses, super-resolution imaging
- MeSH terms
- Animals, Calcium, Cells, Cultured, Cytoskeletal Proteins, Embryo, Mammalian, Exocytosis, Hippocampus, Nerve Tissue Proteins, Synaptic Transmission, Neurons, Neuropeptides, Synapses, Synaptic Vesicles, Rats, Sprague-Dawley, Presynaptic Terminals, Glutamic Acid, GTP-Binding Proteins, RNA, Small Interfering, Adaptor Proteins, Signal Transducing, Vesicular Glutamate Transport Protein 1, Syntaxin 1, Rats
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
