Plasticity-dependent, full detonation at hippocampal mossy fiber-CA3 pyramidal neuron synapses
Open accessAbstract
Mossy fiber synapses on CA3 pyramidal cells are 'conditional detonators' that reliably discharge postsynaptic targets. The 'conditional' nature implies that burst activity in dentate gyrus granule cells is required for detonation. Whether single unitary excitatory postsynaptic potentials (EPSPs) trigger spikes in CA3 neurons remains unknown. Mossy fiber synapses exhibit both pronounced short-term facilitation and uniquely large post-tetanic potentiation (PTP). We tested whether PTP could convert mossy fiber synapses from subdetonator into detonator mode, using a recently developed method to selectively and noninvasively stimulate individual presynaptic terminals in rat brain slices. Unitary EPSPs failed to initiate a spike in CA3 neurons under control conditions, but reliably discharged them after induction of presynaptic short-term plasticity. Remarkably, PTP switched mossy fiber synapses into full detonators for tens of seconds. Plasticity-dependent detonation may be critical for efficient coding, storage, and recall of information in the granule cell-CA3 cell network.
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Chemical potentiation markedly regulates the conditional detonation properties of the synapse.
“Thus, chemical potentiation markedly regulates the conditional detonation properties of the synapse [25,50,51].”
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 [51]
The Results report that potentiation markedly changed detonation: after high-frequency stimulation induced post-tetanic potentiation, the probability of a spike from the first stimulus rose from 0.14 to 0.71 at its peak. The paper supports regulation of detonation by potentiation, but the reported intervention was high-frequency stimulation, not chemical potentiation. (LLM, conf=0.86)
Experimental — accuracy not yet measuredChemical potentiation can switch the hippocampal mossy fiber synapse from a subdetonation into a detonation mode.
“The unitary EPSP recordings (Fig 2) provide direct evidence for this hypothesis, demonstrating that chemical potentiation can switch the hippocampal mossy fiber synapse from a subdetonation into a detonation mode [50,51].”
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 [51]
The Results report that post-tetanic potentiation switched mossy fiber–CA3 synapses from subdetonator to full detonator mode. But the potentiation was induced by high-frequency electrical stimulation (Figure 3), not chemical potentiation; Figure 2 concerns facilitation during a short stimulus train. (LLM, conf=0.88)
Experimental — accuracy not yet measuredHippocampal mossy fiber bouton synapses have low initial release probability.
“The hippocampal MFB synapses are synapses with low initial Pr [51,69,70].”
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 [51]
Facilitation and PTP may lead to conditional detonation or plasticity-dependent detonation at this synapse.
“Previous work showed that facilitation and PTP may lead to conditional detonation or plasticity-dependent detonation at this synapse [21,51].”
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 [51]
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Cites
Dynamics of the Hippocampal Ensemble Code for Space
Wilson, M. A., & McNaughton, B. L. (1993) · Science · doi:10.1126/science.8351520 · Cited by 2,350 · see citing works
Pattern Separation in the Dentate Gyrus and CA3 of the Hippocampus
Leutgeb, J. K., Leutgeb, S., Moser, M.-B., & Moser, E. I. (2007) · Science · doi:10.1126/science.1135801 · Cited by 1,601 · see citing works
Silver, R. A. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2864 · Cited by 481 · see citing works
Distinct short-term plasticity at two excitatory synapses in the hippocampus
Salin, P. A., Scanziani, M., Malenka, R. C., & Nicoll, R. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.23.13304 · Cited by 438 · see citing works
Distinct contribution of adult-born hippocampal granule cells to context encoding
Danielson, N. B., Kaifosh, P., Zaremba, J. D., Lovett-Barron, M., Tsai, J., Denny, C. A., Balough, E. M., Goldberg, A. R., Drew, L. J., Hen, R., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.02.019 · Cited by 352 · see citing works
Differential Mechanisms of Transmission at Three Types of Mossy Fiber Synapse
Toth, K., Suares, G., Lawrence, J. J., Philips-Tansey, E., & McBain, C. J. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-22-08279.2000 · Cited by 262 · see citing works
Structural determinants of transmission at large hippocampal mossy fiber synapses
Rollenhagen, A., Sätzler, K., Rodríguez, E. P., Jonas, P., Frotscher, M., & Lübke, J. H. R. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.1946-07.2007 · Cited by 246 · see citing works
Quantal transmission at mossy fibre targets in the CA3 region of the rat hippocampus
Lawrence, J. J., Grinspan, Z. M., & McBain, C. J. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2003.049551 · Cited by 125 · see citing works
Torborg, C. L., Nakashiba, T., Tonegawa, S., & McBain, C. J. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.3099-10.2010 · Cited by 76 · see citing works
Flagged first, then by citations
Research works printed but not linked: 45
- Acsády L Kamondi A Sík A Freund T Buzsáki G 1998 GABAergic cells are the major postsynaptic targets of mossy fibers in the rat hippocampus Journal of Neuroscience 18 3386 3403 9547246 PMC6792657
- Acuna C Liu X Gonzalez A Südhof TC 2015 RIM-BPs mediate tight coupling of action potentials to Ca2+-triggered neurotransmitter release Neuron 87 1234 1247 10.1016/j.neuron.2015.08.027 26402606 · DOI
- Alcami P Franconville R Llano I Marty A 2012 Measuring the firing rate of high-resistance neurons with cell-attached recording Journal of Neuroscience 32 3118 3130 10.1523/JNEUROSCI.5371-11.2012 22378885 PMC6622012 · DOI
- Amaral DG Dent JA 1981 Development of the mossy fibers of the dentate gyrus: I. A light and electron microscopic study of the mossy fibers and their expansions Journal of Comparative Neurology 195 51 86 10.1002/cne.901950106 7204652 · DOI
- Amaral DG Ishizuka N Claiborne B 1990 Neurons, numbers and the hippocampal network Progress in Brain Research 83 1 11 10.1016/s0079-6123(08)61237-6 2203093 · DOI
- Banke TG McBain CJ 2006 GABAergic input onto CA3 hippocampal interneurons remains shunting throughout development Journal of Neuroscience 26 11720 11725 10.1523/JNEUROSCI.2887-06.2006 17093093 PMC6674795 · DOI · Paper page
- Bischofberger J Engel D Li L Geiger JR Jonas P 2006 Patch-clamp recording from mossy fiber terminals in hippocampal slices Nature Protocols 1 2075 2081 10.1038/nprot.2006.312 17487197 · DOI
- Borst JGG Helmchen F Sakmann B 1995 Pre- and postsynaptic whole-cell recordings in the medial nucleus of the trapezoid body of the rat Journal of Physiology 489 825 840 10.1113/jphysiol.1995.sp021095 8788946 PMC1156851 · DOI
- Brecht M Schneider M Sakmann B Margrie TW 2004 Whisker movements evoked by stimulation of single pyramidal cells in rat motor cortex Nature 427 704 710 10.1038/nature02266 14973477 · DOI
- Brown TH Johnston D 1983 Voltage-clamp analysis of mossy fiber synaptic input to hippocampal neurons Journal of Neurophysiology 50 487 507 6136553
- Buzsáki G 1984 Feed-forward inhibition in the hippocampal formation Progress in Neurobiology 22 131 153 10.1016/0301-0082(84)90023-6 6433403 · DOI · Paper page
- Chicurel ME Harris KM 1992 Three-dimensional analysis of the structure and composition of CA3 branched dendritic spines and their synaptic relationships with mossy fiber boutons in the rat hippocampus Journal of Comparative Neurology 325 169 182 10.1002/cne.903250204 1460112 · DOI · Paper page
- Chu Y Fioravante D Leitges M Regehr WG 2014 Calcium-dependent PKC isoforms have specialized roles in short-term synaptic plasticity Neuron 82 859 871 10.1016/j.neuron.2014.04.003 24794094 PMC4097165 · DOI
- Fries P 2009 Neuronal gamma-band synchronization as a fundamental process in cortical computation Annual Review of Neuroscience 32 209 224 10.1146/annurev.neuro.051508.135603 19400723 · DOI · Paper page
- Galimberti I Gogolla N Alberi S Santos AF Muller D Caroni P 2006 Long-term rearrangements of hippocampal mossy fiber terminal connectivity in the adult regulated by experience Neuron 50 749 763 10.1016/j.neuron.2006.04.026 16731513 · DOI
- Geiger JRP Jonas P 2000 Dynamic control of presynaptic Ca2+ inflow by fast-inactivating K+ channels in hippocampal mossy fiber boutons Neuron 28 927 939 10.1016/S0896-6273(00)00164-1 11163277 · DOI
- Griffith WH 1990 Voltage-clamp analysis of posttetanic potentiation of the mossy fiber to CA3 synapse in hippocampus Journal of Neurophysiology 63 491 501 2158522
- Guzman SJ Schlögl A Schmidt-Hieber C 2014 Stimfit: quantifying electrophysiological data with Python Frontiers in Neuroinformatics 8 e17977 10.3389/fninf.2014.00016 PMC3931263 24600389 · DOI
- Habets RL Borst JGG 2005 Post-tetanic potentiation in the rat calyx of Held synapse Journal of Physiology 564 173 187 10.1113/jphysiol.2004.079160 15695246 PMC1456049 · DOI
- Habets RL Borst JGG 2007 Dynamics of the readily releasable pool during post-tetanic potentiation in the rat calyx of Held synapse Journal of Physiology 581 467 478 10.1113/jphysiol.2006.127365 17363387 PMC2075193 · DOI
- Henze DA Wittner L Buzsáki G 2002 Single granule cells reliably discharge targets in the hippocampal CA3 network in vivo Nature Neuroscience 5 790 795 10.1038/nn887 12118256 · DOI · Paper page
- Jonas P Major G Sakmann B 1993 Quantal components of unitary EPSCs at the mossy fibre synapse on CA3 pyramidal cells of rat hippocampus Journal of Physiology 472 615 663 10.1113/jphysiol.1993.sp019965 7908327 PMC1160505 · DOI · Paper page
- Katz B 1969 The Release of Neurotransmitter Substances Liverpool Liverpool University Press
- Kim S Guzman SJ Hu H Jonas P 2012 Active dendrites support efficient initiation of dendritic spikes in hippocampal CA3 pyramidal neurons Nature Neuroscience 15 600 606 10.1038/nn.3060 22388958 PMC3617474 · DOI
- Koch C Segev I 2000 The role of single neurons in information processing Nature Neuroscience 3 1171 1177 10.1038/81444 11127834 · DOI
- Korogod N Lou X Schneggenburger R 2005 Presynaptic Ca2+ requirements and developmental regulation of posttetanic potentiation at the calyx of Held Journal of Neuroscience 25 5127 5137 10.1523/JNEUROSCI.1295-05.2005 15917453 PMC6724817 · DOI
- Langdon RB Johnson JW Barrionuevo G 1995 Posttetanic potentiation and presynaptically induced long-term potentiation at the mossy fiber synapse in rat hippocampus Journal of Neurobiology 26 370 385 10.1002/neu.480260309 7775970 · DOI
- Lisman JE 1999 Relating hippocampal circuitry to function: recall of memory sequences by reciprocal dentate-CA3 interactions Neuron 22 233 242 10.1016/S0896-6273(00)81085-5 10069330 · DOI · Paper page
- Liu X Ramirez S Pang PT Puryear CB Govindarajan A Deisseroth K Tonegawa S 2012 Optogenetic stimulation of a hippocampal engram activates fear memory recall Nature 484 381 385 10.1038/nature11028 22441246 PMC3331914 · DOI
- London M Häusser M 2005 Dendritic computation Annual Review Neuroscience 28 503 532 10.1146/annurev.neuro.28.061604.135703 16033324 · DOI · Paper page
- Mori M Abegg MH Gähwiler BH Gerber U 2004 A frequency-dependent switch from inhibition to excitation in a hippocampal unitary circuit Nature 431 453 456 10.1038/nature02854 15386013 · DOI
- Neunuebel JP Knierim JJ 2012 Spatial firing correlates of physiologically distinct cell types of the rat dentate gyrus Journal of Neuroscience 32 3848 3858 10.1523/JNEUROSCI.6038-11.2012 22423105 PMC3321836 · DOI
- Nicoll RA Schmitz D 2005 Synaptic plasticity at hippocampal mossy fibre synapses Nature Reviews Neuroscience 6 863 876 10.1038/nrn1786 16261180 · DOI · Paper page
- Patton PE McNaughton B 1995 Connection matrix of the hippocampal formation: I. The dentate gyrus Hippocampus 5 245 286 10.1002/hipo.450050402 8589792 · DOI
- Pelkey KA McBain CJ 2005 How to dismantle a detonator synapse Neuron 45 327 329 10.1016/j.neuron.2005.01.018 15694316 · DOI
- Perkins KL 2006 Cell-attached voltage-clamp and current-clamp recording and stimulation techniques in brain slices Journal of Neuroscience Methods 154 1 18 10.1016/j.jneumeth.2006.02.010 16554092 PMC2373773 · DOI
- Pernía-Andrade AJ Jonas P 2014 Theta-gamma-modulated synaptic currents in hippocampal granule cells in vivo define a mechanism for network oscillations Neuron 81 140 152 10.1016/j.neuron.2013.09.046 24333053 PMC3909463 · DOI
- Pilz GA Carta S Stäuble A Ayaz A Jessberger S Helmchen F 2016 Functional imaging of dentate granule cells in the adult mouse hippocampus Journal of Neuroscience 36 7407 7414 10.1523/JNEUROSCI.3065-15.2016 27413151 PMC6705545 · DOI
- Quiroga RQ Reddy L Kreiman G Koch C Fried I 2005 Invariant visual representation by single neurons in the human brain Nature 435 1102 1107 10.1038/nature03687 15973409 · DOI · Paper page
- Szabadics J Soltesz I 2009 Functional specificity of mossy fiber innervation of GABAergic cells in the hippocampus Journal of Neuroscience 29 4239 4251 10.1523/JNEUROSCI.5390-08.2009 19339618 PMC6665380 · DOI
- Treves A Rolls ET 1994 Computational analysis of the role of the hippocampus in memory Hippocampus 4 374 391 10.1002/hipo.450040319 7842058 · DOI · Paper page
- Urban NN Henze DA Barrionuevo G 2001 Revisiting the role of the hippocampal mossy fiber synapse Hippocampus 11 408 417 10.1002/hipo.1055 11530845 · DOI
- Vyleta NP Jonas P 2014 Loose coupling between Ca2+ channels and release sensors at a plastic hippocampal synapse Science 343 665 670 10.1126/science.1244811 24503854 · DOI · Paper page
- Vyleta NP Borges-Merjane C Zhang X Jonas P 2016 Plasticity-dependent, full detonation at hippocampal mossy fiber-CA3 pyramidal neuron synapses Society for Neuroscience Abstracts 504 09 PMC5079747 27780032
- Zucker RS Regehr WG 2002 Short-term synaptic plasticity Annual Review of Physiology 64 355 405 10.1146/annurev.physiol.64.092501.114547 11826273 · DOI · Paper page
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Shahoha, M., Cohen, R., Ben-Simon, Y., & Ashery, U. (2022) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2022.861215 · Cited by 46 · see citing works
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Vandael, D., & Jonas, P. (2024) · Science · doi:10.1126/science.adg6757 · Cited by 45 · see citing works
Martinello, K., Giacalone, E., Migliore, M., Brown, D. A., & Shah, M. M. (2019) · Communications Biology · doi:10.1038/s42003-019-0408-4 · Cited by 32 · see citing works
Kim, O., Okamoto, Y., Kaufmann, W. A., Brose, N., Shigemoto, R., & Jonas, P. (2024) · PLOS Biology · doi:10.1371/journal.pbio.3002879 · Cited by 15 · see citing works
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- Authors
- Vyleta, N. P., Borges-Merjane, C., & Jonas, P.
- Affiliations
- Institute of Science and Technology Austria (AT)
- Institute of Science and Technology Austria, Klosterneuburg, Austria
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2016-10-25
- Volume
- 5
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC5079747
- OpenAlex
- W2535386109
- Cited by
- 91
- References
- 9
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 10 · 2023: 8 · 2022: 7 · 2021: 14 · 2020: 10 · 2019: 13 · 2018: 9 · 2017: 5 · 2016: 1
- FWCI
- 5.25
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (2T32HL083808)
- People Programme (291734)
- European Research Council (268548, 692692)
- Austrian Science Fund (FWF P 24909-B24)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- mossy fiber synapses, CA3 pyramidal cells, post-tetanic potentiation, short-term plasticity, excitatory postsynaptic potentials, dentate gyrus granule cells, hippocampus, synaptic facilitation
- MeSH terms
- Animals, Neuronal Plasticity, Synapses, Pyramidal Cells, Mossy Fibers, Hippocampal, Excitatory Postsynaptic Potentials, Rats, CA3 Region, Hippocampal
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