[{"doi":"10.1073/pnas.2301449121","related_material":{"link":[{"description":"News on ISTA Website","relation":"press_release","url":"https://ista.ac.at/en/news/neuronal-insights-flash-and-freeze-fracture/"}],"record":[{"status":"public","relation":"research_data","id":"13173"},{"status":"public","relation":"dissertation_contains","id":"19271"}]},"acknowledgement":"We thank Erwin Neher and Ipe Ninan for critical comments on the manuscript. This project has received funding from the European Research Council (ERC) and European Commission, under the European Union’s Horizon 2020 research and innovation program (ERC grant agreement no. 694539 to R.S. and the Marie Skłodowska-Curie grant agreement no. 665385 to C.Ö.). This study was supported by the Cooperative Study Program of Center for Animal Resources and Collaborative Study of NINS. We thank Kohgaku Eguchi for statistical analysis, Yu Kasugai for additional EM imaging, Robert Beattie for the design of the slice recovery chamber for Flash and Freeze experiments, Todor Asenov from the ISTA machine shop for custom part preparations for high-pressure freezing, the ISTA preclinical facility for animal caretaking, and the ISTA EM facilities for technical support.","file":[{"success":1,"file_id":"15110","file_size":13648221,"file_name":"2024_PNAS_Koppensteiner.pdf","checksum":"b25b2a057c266ff317a48b0d54d6fc8a","creator":"dernst","relation":"main_file","date_updated":"2024-03-12T13:42:42Z","date_created":"2024-03-12T13:42:42Z","access_level":"open_access","content_type":"application/pdf"}],"project":[{"_id":"25CA28EA-B435-11E9-9278-68D0E5697425","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","grant_number":"694539","call_identifier":"H2020"},{"call_identifier":"H2020","name":"International IST Doctoral Program","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"}],"researchdata_availability":"yes","publication":"Proceedings of the National Academy of Sciences of the United States of America","article_type":"original","abstract":[{"lang":"eng","text":"GABAB receptor (GBR) activation inhibits neurotransmitter release in axon terminals in the brain, except in medial habenula (MHb) terminals, which show robust potentiation. However, mechanisms underlying this enigmatic potentiation remain elusive. Here, we report that GBR activation on MHb terminals induces an activity-dependent transition from a facilitating, tonic to a depressing, phasic neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked synaptic vesicles (SVs) at the presynaptic active zone (AZ). Strikingly, the depressing phasic release exhibits looser coupling distance than the tonic release. Furthermore, the tonic and phasic release are selectively affected by deletion of synaptoporin (SPO) and Ca\r\n            <jats:sup>2+</jats:sup>\r\n            -dependent activator protein for secretion 2 (CAPS2), respectively. SPO modulates augmentation, the short-term plasticity associated with tonic release, and CAPS2 retains the increased RRP for initial responses in phasic response trains. The cytosolic protein CAPS2 showed a SV-associated distribution similar to the vesicular transmembrane protein SPO, and they were colocalized in the same terminals. We developed the “Flash and Freeze-fracture” method, and revealed the release of SPO-associated vesicles in both tonic and phasic modes and activity-dependent recruitment of CAPS2 to the AZ during phasic release, which lasted several minutes. Overall, these results indicate that GBR activation translocates CAPS2 to the AZ along with the fusion of CAPS2-associated SVs, contributing to persistency of the RRP increase. Thus, we identified structural and molecular mechanisms underlying tonic and phasic neurotransmitter release and their transition by GBR activation in MHb terminals."}],"quality_controlled":"1","article_processing_charge":"Yes (in subscription journal)","ec_funded":1,"fulldoi":"https://doi.org/10.1073/pnas.2301449121","type":"journal_article","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png"},"publisher":"National Academy of Sciences","scopus_import":"1","corr_author":"1","publication_status":"published","oa_version":"Published Version","article_number":"e2301449121","volume":121,"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"date_created":"2024-03-05T09:23:55Z","citation":{"mla":"Koppensteiner, Peter, et al. “GABAB Receptors Induce Phasic Release from Medial Habenula Terminals through Activity-Dependent Recruitment of Release-Ready Vesicles.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 121, no. 8, e2301449121, National Academy of Sciences, 2024, doi:<a href=\"https://doi.org/10.1073/pnas.2301449121\">10.1073/pnas.2301449121</a>.","short":"P. Koppensteiner, P. Bhandari, C. Önal, C. Borges Merjane, E. Le Monnier, U. Roy, Y. Nakamura, T. Sadakata, M. Sanbo, M. Hirabayashi, J. Rhee, N. Brose, P.M. Jonas, R. Shigemoto, Proceedings of the National Academy of Sciences of the United States of America 121 (2024).","apa":"Koppensteiner, P., Bhandari, P., Önal, C., Borges Merjane, C., Le Monnier, E., Roy, U., … Shigemoto, R. (2024). GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2301449121\">https://doi.org/10.1073/pnas.2301449121</a>","ama":"Koppensteiner P, Bhandari P, Önal C, et al. GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2024;121(8). doi:<a href=\"https://doi.org/10.1073/pnas.2301449121\">10.1073/pnas.2301449121</a>","ieee":"P. Koppensteiner <i>et al.</i>, “GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 121, no. 8. National Academy of Sciences, 2024.","ista":"Koppensteiner P, Bhandari P, Önal C, Borges Merjane C, Le Monnier E, Roy U, Nakamura Y, Sadakata T, Sanbo M, Hirabayashi M, Rhee J, Brose N, Jonas PM, Shigemoto R. 2024. GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. Proceedings of the National Academy of Sciences of the United States of America. 121(8), e2301449121.","chicago":"Koppensteiner, Peter, Pradeep Bhandari, Cihan Önal, Carolina Borges Merjane, Elodie Le Monnier, Utsa Roy, Yukihiro Nakamura, et al. “GABAB Receptors Induce Phasic Release from Medial Habenula Terminals through Activity-Dependent Recruitment of Release-Ready Vesicles.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences, 2024. <a href=\"https://doi.org/10.1073/pnas.2301449121\">https://doi.org/10.1073/pnas.2301449121</a>."},"OA_type":"hybrid","year":"2024","department":[{"_id":"RySh"},{"_id":"PeJo"}],"status":"public","APC_amount":"5887,8 EUR","has_accepted_license":"1","oa":1,"author":[{"first_name":"Peter","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","last_name":"Koppensteiner","orcid":"0000-0002-3509-1948","full_name":"Koppensteiner, Peter"},{"id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","last_name":"Bhandari","first_name":"Pradeep","orcid":"0000-0003-0863-4481","full_name":"Bhandari, Pradeep"},{"orcid":"0000-0002-2771-2011","full_name":"Önal, Hüseyin C","first_name":"Hüseyin C","id":"4659D740-F248-11E8-B48F-1D18A9856A87","last_name":"Önal"},{"last_name":"Borges Merjane","id":"4305C450-F248-11E8-B48F-1D18A9856A87","first_name":"Carolina","full_name":"Borges Merjane, Carolina","orcid":"0000-0003-0005-401X"},{"first_name":"Elodie","id":"3B59276A-F248-11E8-B48F-1D18A9856A87","last_name":"Le Monnier","full_name":"Le Monnier, Elodie"},{"last_name":"Roy","id":"4d26cf11-5355-11ee-ae5a-eb05e255b9b2","first_name":"Utsa","full_name":"Roy, Utsa"},{"first_name":"Yukihiro","last_name":"Nakamura","full_name":"Nakamura, Yukihiro"},{"last_name":"Sadakata","first_name":"Tetsushi","full_name":"Sadakata, Tetsushi"},{"full_name":"Sanbo, Makoto","first_name":"Makoto","last_name":"Sanbo"},{"full_name":"Hirabayashi, Masumi","last_name":"Hirabayashi","first_name":"Masumi"},{"full_name":"Rhee, JeongSeop","first_name":"JeongSeop","last_name":"Rhee"},{"full_name":"Brose, Nils","first_name":"Nils","last_name":"Brose"},{"orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M"},{"first_name":"Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444"}],"external_id":{"pmid":["38346189"],"isi":["001208567300006"]},"month":"02","date_published":"2024-02-20T00:00:00Z","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","date_updated":"2026-10-25T23:31:31Z","ddc":["570"],"das_tickbox":"1","OA_place":"publisher","file_date_updated":"2024-03-12T13:42:42Z","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"supplementarymaterial":"yes","intvolume":"       121","_id":"15084","language":[{"iso":"eng"}],"day":"20","issue":"8","isi":1,"pmid":1,"title":"GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles"},{"fulldoi":"https://doi.org/10.1371/journal.pone.0277148","ec_funded":1,"type":"journal_article","license":"https://creativecommons.org/licenses/by/4.0/","scopus_import":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"publisher":"Public Library of Science","publication_status":"published","oa_version":"Published Version","acknowledged_ssus":[{"_id":"EM-Fac"}],"article_number":"e0277148","volume":18,"acknowledgement":"We thank the IST Austria Electron Microscopy Facility for technical support, and Diccon Coyle, Andrea Lőrincz and Zoltan Nusser for their helpful comments and discussions.\r\nFunding for JSR and RAS was from the Wellcome Trust (203048; 224499; https://\r\nwellcome.org/). RAS is in receipt of a Wellcome Trust Principal Research Fellowship (224499).\r\nFunding for CBM and PJ was from Fond zur Förderung der Wissenschaftlichen Forschung (V\r\n739-B27 Elise-Richter Programme to CBM, Z 312-B27 Wittgenstein Award to PJ; \r\nhttps://www.fwf.ac.at). PJ received funding from the European Research Council (ERC; https://erc.europa.eu) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 692692). NH was supported by a European\r\nResearch Council Advanced Grant (ERC-AG787157).","doi":"10.1371/journal.pone.0277148","file":[{"date_updated":"2023-03-27T06:51:09Z","date_created":"2023-03-27T06:51:09Z","content_type":"application/pdf","access_level":"open_access","file_size":7290413,"checksum":"2380331ec27cc87808826fc64419ac1c","creator":"dernst","file_name":"2023_PLoSOne_Rothman.pdf","file_id":"12770","success":1,"relation":"main_file"}],"abstract":[{"lang":"eng","text":"Stereological methods for estimating the 3D particle size and density from 2D projections are essential to many research fields. These methods are, however, prone to errors arising from undetected particle profiles due to sectioning and limited resolution, known as ‘lost caps’. A potential solution developed by Keiding, Jensen, and Ranek in 1972, which we refer to as the Keiding model, accounts for lost caps by quantifying the smallest detectable profile in terms of its limiting ‘cap angle’ (ϕ), a size-independent measure of a particle’s distance from the section surface. However, this simple solution has not been widely adopted nor tested. Rather, model-independent design-based stereological methods, which do not explicitly account for lost caps, have come to the fore. Here, we provide the first experimental validation of the Keiding model by comparing the size and density of particles estimated from 2D projections with direct measurement from 3D EM reconstructions of the same tissue. We applied the Keiding model to estimate the size and density of somata, nuclei and vesicles in the cerebellum of mice and rats, where high packing density can be problematic for design-based methods. Our analysis reveals a Gaussian distribution for ϕ rather than a single value. Nevertheless, curve fits of the Keiding model to the 2D diameter distribution accurately estimate the mean ϕ and 3D diameter distribution. While systematic testing using simulations revealed an upper limit to determining ϕ, our analysis shows that estimated ϕ can be used to determine the 3D particle density from the 2D density under a wide range of conditions, and this method is potentially more accurate than minimum-size-based lost-cap corrections and disector methods. Our results show the Keiding model provides an efficient means of accurately estimating the size and density of particles from 2D projections even under conditions of a high density."}],"article_type":"original","publication":"PLoS ONE","project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312","name":"Synaptic communication in neuronal microcircuits"},{"call_identifier":"FWF","name":"Structural plasticity at mossy fiber-CA3 synapses","grant_number":"V00739","_id":"2696E7FE-B435-11E9-9278-68D0E5697425"}],"article_processing_charge":"No","quality_controlled":"1","date_published":"2023-03-17T00:00:00Z","date_updated":"2025-04-23T08:50:50Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"file_date_updated":"2023-03-27T06:51:09Z","publication_identifier":{"eissn":["1932-6203"]},"intvolume":"        18","day":"17","isi":1,"issue":"3 March","pmid":1,"language":[{"iso":"eng"}],"_id":"12759","title":"Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy","department":[{"_id":"PeJo"}],"date_created":"2023-03-26T22:01:07Z","citation":{"ista":"Rothman JS, Borges Merjane C, Holderith N, Jonas PM, Angus Silver R. 2023. Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy. PLoS ONE. 18(3 March), e0277148.","chicago":"Rothman, Jason Seth, Carolina Borges Merjane, Noemi Holderith, Peter M Jonas, and R. Angus Silver. “Validation of a Stereological Method for Estimating Particle Size and Density from 2D Projections with High Accuracy.” <i>PLoS ONE</i>. Public Library of Science, 2023. <a href=\"https://doi.org/10.1371/journal.pone.0277148\">https://doi.org/10.1371/journal.pone.0277148</a>.","ieee":"J. S. Rothman, C. Borges Merjane, N. Holderith, P. M. Jonas, and R. Angus Silver, “Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy,” <i>PLoS ONE</i>, vol. 18, no. 3 March. Public Library of Science, 2023.","mla":"Rothman, Jason Seth, et al. “Validation of a Stereological Method for Estimating Particle Size and Density from 2D Projections with High Accuracy.” <i>PLoS ONE</i>, vol. 18, no. 3 March, e0277148, Public Library of Science, 2023, doi:<a href=\"https://doi.org/10.1371/journal.pone.0277148\">10.1371/journal.pone.0277148</a>.","ama":"Rothman JS, Borges Merjane C, Holderith N, Jonas PM, Angus Silver R. Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy. <i>PLoS ONE</i>. 2023;18(3 March). doi:<a href=\"https://doi.org/10.1371/journal.pone.0277148\">10.1371/journal.pone.0277148</a>","short":"J.S. Rothman, C. Borges Merjane, N. Holderith, P.M. Jonas, R. Angus Silver, PLoS ONE 18 (2023).","apa":"Rothman, J. S., Borges Merjane, C., Holderith, N., Jonas, P. M., &#38; Angus Silver, R. (2023). Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy. <i>PLoS ONE</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pone.0277148\">https://doi.org/10.1371/journal.pone.0277148</a>"},"year":"2023","status":"public","author":[{"last_name":"Rothman","first_name":"Jason Seth","full_name":"Rothman, Jason Seth"},{"orcid":"0000-0003-0005-401X","full_name":"Borges Merjane, Carolina","first_name":"Carolina","last_name":"Borges Merjane","id":"4305C450-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Holderith, Noemi","last_name":"Holderith","first_name":"Noemi"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","first_name":"Peter M","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804"},{"full_name":"Angus Silver, R.","first_name":"R.","last_name":"Angus Silver"}],"oa":1,"has_accepted_license":"1","month":"03","external_id":{"isi":["001024737400001"],"pmid":["36930689"]}},{"external_id":{"pmid":["33616036"]},"month":"02","oa":1,"has_accepted_license":"1","author":[{"full_name":"Balmer, Timothy S","first_name":"Timothy S","last_name":"Balmer"},{"orcid":"0000-0003-0005-401X","full_name":"Borges Merjane, Carolina","first_name":"Carolina","last_name":"Borges Merjane","id":"4305C450-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Laurence O","last_name":"Trussell","full_name":"Trussell, Laurence O"}],"status":"public","year":"2021","date_created":"2024-04-03T07:58:11Z","citation":{"mla":"Balmer, Timothy S., et al. “Incomplete Removal of Extracellular Glutamate Controls Synaptic Transmission and Integration at a Cerebellar Synapse.” <i>ELife</i>, vol. 10, e63819, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/elife.63819\">10.7554/elife.63819</a>.","ama":"Balmer TS, Borges Merjane C, Trussell LO. Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/elife.63819\">10.7554/elife.63819</a>","apa":"Balmer, T. S., Borges Merjane, C., &#38; Trussell, L. O. (2021). Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.63819\">https://doi.org/10.7554/elife.63819</a>","short":"T.S. Balmer, C. Borges Merjane, L.O. Trussell, ELife 10 (2021).","ista":"Balmer TS, Borges Merjane C, Trussell LO. 2021. Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse. eLife. 10, e63819.","chicago":"Balmer, Timothy S, Carolina Borges Merjane, and Laurence O Trussell. “Incomplete Removal of Extracellular Glutamate Controls Synaptic Transmission and Integration at a Cerebellar Synapse.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/elife.63819\">https://doi.org/10.7554/elife.63819</a>.","ieee":"T. S. Balmer, C. Borges Merjane, and L. O. Trussell, “Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021."},"department":[{"_id":"PeJo"}],"title":"Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"language":[{"iso":"eng"}],"_id":"15273","pmid":1,"day":"22","publication_identifier":{"issn":["2050-084X"]},"intvolume":"        10","file_date_updated":"2024-04-09T11:13:07Z","date_published":"2021-02-22T00:00:00Z","ddc":["570"],"date_updated":"2024-04-09T11:15:01Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","quality_controlled":"1","article_processing_charge":"Yes","publication":"eLife","abstract":[{"lang":"eng","text":"Synapses of glutamatergic mossy fibers (MFs) onto cerebellar unipolar brush cells (UBCs) generate slow excitatory (ON) or inhibitory (OFF) postsynaptic responses dependent on the complement of glutamate receptors expressed on the UBC’s large dendritic brush. Using mouse brain slice recording and computational modeling of synaptic transmission, we found that substantial glutamate is maintained in the UBC synaptic cleft, sufficient to modify spontaneous firing in OFF UBCs and tonically desensitize AMPARs of ON UBCs. The source of this ambient glutamate was spontaneous, spike-independent exocytosis from the MF terminal, and its level was dependent on activity of glutamate transporters EAAT1–2. Increasing levels of ambient glutamate shifted the polarity of evoked synaptic responses in ON UBCs and altered the phase of responses to in vivo-like synaptic activity. Unlike classical fast synapses, receptors at the UBC synapse are virtually always exposed to a significant level of glutamate, which varies in a graded manner during transmission."}],"article_type":"original","file":[{"file_id":"15307","success":1,"file_name":"2021_eLife_Balmer.pdf","checksum":"bbd4de2e54b7fbc11fba14f59e87fe3f","file_size":6997954,"creator":"dernst","relation":"main_file","date_updated":"2024-04-09T11:13:07Z","date_created":"2024-04-09T11:13:07Z","access_level":"open_access","content_type":"application/pdf"}],"doi":"10.7554/elife.63819","volume":10,"article_number":"e63819","oa_version":"Published Version","publication_status":"published","publisher":"eLife Sciences Publications","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"type":"journal_article","fulldoi":"https://doi.org/10.7554/elife.63819"},{"acknowledged_ssus":[{"_id":"M-Shop"}],"page":"2947–2967","volume":16,"publication_status":"published","oa_version":"Submitted Version","corr_author":"1","scopus_import":"1","publisher":"Springer Nature","ec_funded":1,"fulldoi":"https://doi.org/10.1038/s41596-021-00526-0","type":"journal_article","article_processing_charge":"No","quality_controlled":"1","abstract":[{"text":"Rigorous investigation of synaptic transmission requires analysis of unitary synaptic events by simultaneous recording from presynaptic terminals and postsynaptic target neurons. However, this has been achieved at only a limited number of model synapses, including the squid giant synapse and the mammalian calyx of Held. Cortical presynaptic terminals have been largely inaccessible to direct presynaptic recording, due to their small size. Here, we describe a protocol for improved subcellular patch-clamp recording in rat and mouse brain slices, with the synapse in a largely intact environment. Slice preparation takes ~2 h, recording ~3 h and post hoc morphological analysis 2 d. Single presynaptic hippocampal mossy fiber terminals are stimulated minimally invasively in the bouton-attached configuration, in which the cytoplasmic content remains unperturbed, or in the whole-bouton configuration, in which the cytoplasmic composition can be precisely controlled. Paired pre–postsynaptic recordings can be integrated with biocytin labeling and morphological analysis, allowing correlative investigation of synapse structure and function. Paired recordings can be obtained from mossy fiber terminals in slices from both rats and mice, implying applicability to genetically modified synapses. Paired recordings can also be performed together with axon tract stimulation or optogenetic activation, allowing comparison of unitary and compound synaptic events in the same target cell. Finally, paired recordings can be combined with spontaneous event analysis, permitting collection of miniature events generated at a single identified synapse. In conclusion, the subcellular patch-clamp techniques detailed here should facilitate analysis of biophysics, plasticity and circuit function of cortical synapses in the mammalian central nervous system.","lang":"eng"}],"article_type":"original","publication":"Nature Protocols","project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","call_identifier":"H2020"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312","name":"Synaptic communication in neuronal microcircuits","call_identifier":"FWF"},{"grant_number":"V00739","name":"Structural plasticity at mossy fiber-CA3 synapses","_id":"2696E7FE-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"file":[{"relation":"main_file","file_id":"9639","creator":"cziletti","file_size":38574802,"checksum":"7eb580abd8893cdb0b410cf41bc8c263","file_name":"VandaeletalAuthorVersion2021.pdf","access_level":"open_access","embargo":"2021-12-01","content_type":"application/pdf","date_created":"2021-07-08T12:27:55Z","date_updated":"2021-12-02T23:30:05Z"}],"acknowledgement":"This project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award to P.J., V 739-B27 to C.B.M.). We are grateful to F. Marr and C. Altmutter for excellent technical assistance and cell reconstruction, E. Kralli-Beller for manuscript editing, and the Scientific Service Units of IST Austria, especially T. Asenov and Miba machine shop, for maximally efficient support.","doi":"10.1038/s41596-021-00526-0","title":"Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses","day":"01","pmid":1,"issue":"6","isi":1,"language":[{"iso":"eng"}],"_id":"9438","file_date_updated":"2021-12-02T23:30:05Z","publication_identifier":{"eissn":["1750-2799"],"issn":["1754-2189"]},"intvolume":"        16","date_published":"2021-06-01T00:00:00Z","date_updated":"2025-04-22T22:30:43Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"month":"06","external_id":{"pmid":["33990799"],"isi":["000650528700003"]},"author":[{"full_name":"Vandael, David H","orcid":"0000-0001-7577-1676","last_name":"Vandael","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","first_name":"David H"},{"full_name":"Okamoto, Yuji","orcid":"0000-0003-0408-6094","id":"3337E116-F248-11E8-B48F-1D18A9856A87","last_name":"Okamoto","first_name":"Yuji"},{"id":"4305C450-F248-11E8-B48F-1D18A9856A87","last_name":"Borges Merjane","first_name":"Carolina","full_name":"Borges Merjane, Carolina","orcid":"0000-0003-0005-401X"},{"full_name":"Vargas Barroso, Victor M","id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87","last_name":"Vargas Barroso","first_name":"Victor M"},{"first_name":"Benjamin","last_name":"Suter","id":"4952F31E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9885-6936","full_name":"Suter, Benjamin"},{"orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","first_name":"Peter M"}],"oa":1,"has_accepted_license":"1","status":"public","department":[{"_id":"PeJo"}],"date_created":"2021-05-30T22:01:24Z","citation":{"chicago":"Vandael, David H, Yuji Okamoto, Carolina Borges Merjane, Victor M Vargas Barroso, Benjamin Suter, and Peter M Jonas. “Subcellular Patch-Clamp Techniques for Single-Bouton Stimulation and Simultaneous Pre- and Postsynaptic Recording at Cortical Synapses.” <i>Nature Protocols</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41596-021-00526-0\">https://doi.org/10.1038/s41596-021-00526-0</a>.","ista":"Vandael DH, Okamoto Y, Borges Merjane C, Vargas Barroso VM, Suter B, Jonas PM. 2021. Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses. Nature Protocols. 16(6), 2947–2967.","ieee":"D. H. Vandael, Y. Okamoto, C. Borges Merjane, V. M. Vargas Barroso, B. Suter, and P. M. Jonas, “Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses,” <i>Nature Protocols</i>, vol. 16, no. 6. Springer Nature, pp. 2947–2967, 2021.","mla":"Vandael, David H., et al. “Subcellular Patch-Clamp Techniques for Single-Bouton Stimulation and Simultaneous Pre- and Postsynaptic Recording at Cortical Synapses.” <i>Nature Protocols</i>, vol. 16, no. 6, Springer Nature, 2021, pp. 2947–2967, doi:<a href=\"https://doi.org/10.1038/s41596-021-00526-0\">10.1038/s41596-021-00526-0</a>.","ama":"Vandael DH, Okamoto Y, Borges Merjane C, Vargas Barroso VM, Suter B, Jonas PM. Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses. <i>Nature Protocols</i>. 2021;16(6):2947–2967. doi:<a href=\"https://doi.org/10.1038/s41596-021-00526-0\">10.1038/s41596-021-00526-0</a>","apa":"Vandael, D. H., Okamoto, Y., Borges Merjane, C., Vargas Barroso, V. M., Suter, B., &#38; Jonas, P. M. (2021). Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses. <i>Nature Protocols</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41596-021-00526-0\">https://doi.org/10.1038/s41596-021-00526-0</a>","short":"D.H. Vandael, Y. Okamoto, C. Borges Merjane, V.M. Vargas Barroso, B. Suter, P.M. Jonas, Nature Protocols 16 (2021) 2947–2967."},"year":"2021"},{"status":"public","department":[{"_id":"PeJo"}],"citation":{"mla":"Vandael, David H., et al. “Short-Term Plasticity at Hippocampal Mossy Fiber Synapses Is Induced by Natural Activity Patterns and Associated with Vesicle Pool Engram Formation.” <i>Neuron</i>, vol. 107, no. 3, Elsevier, 2020, pp. 509–21, doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.05.013\">10.1016/j.neuron.2020.05.013</a>.","short":"D.H. Vandael, C. Borges Merjane, X. Zhang, P.M. Jonas, Neuron 107 (2020) 509–521.","apa":"Vandael, D. H., Borges Merjane, C., Zhang, X., &#38; Jonas, P. M. (2020). Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2020.05.013\">https://doi.org/10.1016/j.neuron.2020.05.013</a>","ama":"Vandael DH, Borges Merjane C, Zhang X, Jonas PM. Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation. <i>Neuron</i>. 2020;107(3):509-521. doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.05.013\">10.1016/j.neuron.2020.05.013</a>","ieee":"D. H. Vandael, C. Borges Merjane, X. Zhang, and P. M. Jonas, “Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation,” <i>Neuron</i>, vol. 107, no. 3. Elsevier, pp. 509–521, 2020.","chicago":"Vandael, David H, Carolina Borges Merjane, Xiaomin Zhang, and Peter M Jonas. “Short-Term Plasticity at Hippocampal Mossy Fiber Synapses Is Induced by Natural Activity Patterns and Associated with Vesicle Pool Engram Formation.” <i>Neuron</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.neuron.2020.05.013\">https://doi.org/10.1016/j.neuron.2020.05.013</a>.","ista":"Vandael DH, Borges Merjane C, Zhang X, Jonas PM. 2020. Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation. Neuron. 107(3), 509–521."},"date_created":"2020-06-22T13:29:05Z","year":"2020","month":"08","external_id":{"pmid":["32492366"],"isi":["000556135600004"]},"author":[{"last_name":"Vandael","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","first_name":"David H","orcid":"0000-0001-7577-1676","full_name":"Vandael, David H"},{"full_name":"Borges Merjane, Carolina","orcid":"0000-0003-0005-401X","last_name":"Borges Merjane","id":"4305C450-F248-11E8-B48F-1D18A9856A87","first_name":"Carolina"},{"full_name":"Zhang, Xiaomin","first_name":"Xiaomin","last_name":"Zhang","id":"423EC9C2-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804"}],"has_accepted_license":"1","oa":1,"file_date_updated":"2020-11-25T11:23:02Z","publication_identifier":{"eissn":["10974199"],"issn":["0896-6273"]},"intvolume":"       107","date_updated":"2025-04-15T08:29:09Z","ddc":["570"],"date_published":"2020-08-05T00:00:00Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","title":"Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation","day":"05","issue":"3","pmid":1,"isi":1,"_id":"8001","language":[{"iso":"eng"}],"file":[{"relation":"main_file","success":1,"file_id":"8811","file_name":"2020_Neuron_Vandael.pdf","checksum":"4030b2be0c9625d54694a1e9fb00305e","creator":"dernst","file_size":4390833,"access_level":"open_access","content_type":"application/pdf","date_created":"2020-11-25T11:23:02Z","date_updated":"2020-11-25T11:23:02Z"}],"acknowledgement":"This project received funding from the European Research Council (ERC) under the European Union Horizon 2020 Research and Innovation Program (grant agreement 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung ( Z 312-B27 , Wittgenstein award to P.J. and V 739-B27 to C.B.-M.). We thank Drs. Jozsef Csicsvari, Jose Guzman, Erwin Neher, and Ryuichi Shigemoto for commenting on earlier versions of the manuscript. We are grateful to Walter Kaufmann, Daniel Gütl, and Vanessa Zheden for EM training; Alois Schlögl for programming; Florian Marr for excellent technical assistance and cell reconstruction; Christina Altmutter for technical help; Eleftheria Kralli-Beller for manuscript editing; Taija Makinen for providing the Prox1-CreERT2 mouse line; and the Scientific Service Units of IST Austria for support.","related_material":{"link":[{"description":"News on IST Homepage","url":"https://ist.ac.at/en/news/possible-physical-trace-of-short-term-memory-found/","relation":"press_release"}]},"doi":"10.1016/j.neuron.2020.05.013","article_processing_charge":"No","quality_controlled":"1","abstract":[{"text":"Post-tetanic potentiation (PTP) is an attractive candidate mechanism for hippocampus-dependent short-term memory. Although PTP has a uniquely large magnitude at hippocampal mossy fiber-CA3 pyramidal neuron synapses, it is unclear whether it can be induced by natural activity and whether its lifetime is sufficient to support short-term memory. We combined in vivo recordings from granule cells (GCs), in vitro paired recordings from mossy fiber terminals and postsynaptic CA3 neurons, and “flash and freeze” electron microscopy. PTP was induced at single synapses and showed a low induction threshold adapted to sparse GC activity in vivo. PTP was mainly generated by enlargement of the readily releasable pool of synaptic vesicles, allowing multiplicative interaction with other plasticity forms. PTP was associated with an increase in the docked vesicle pool, suggesting formation of structural “pool engrams.” Absence of presynaptic activity extended the lifetime of the potentiation, enabling prolonged information storage in the hippocampal network.","lang":"eng"}],"article_type":"original","publication":"Neuron","project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","call_identifier":"H2020"},{"call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"Synaptic communication in neuronal microcircuits","grant_number":"Z00312"},{"name":"Structural plasticity at mossy fiber-CA3 synapses","grant_number":"V00739","_id":"2696E7FE-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"scopus_import":"1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png"},"publisher":"Elsevier","ec_funded":1,"fulldoi":"https://doi.org/10.1016/j.neuron.2020.05.013","type":"journal_article","acknowledged_ssus":[{"_id":"SSU"}],"page":"509-521","volume":107,"publication_status":"published","oa_version":"Published Version","corr_author":"1"},{"status":"public","year":"2020","date_created":"2020-02-10T15:59:45Z","citation":{"ieee":"C. Borges Merjane, O. Kim, and P. M. Jonas, “Functional electron microscopy (‘Flash and Freeze’) of identified cortical synapses in acute brain slices,” <i>Neuron</i>, vol. 105. Elsevier, pp. 992–1006, 2020.","ista":"Borges Merjane C, Kim O, Jonas PM. 2020. Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices. Neuron. 105, 992–1006.","chicago":"Borges Merjane, Carolina, Olena Kim, and Peter M Jonas. “Functional Electron Microscopy (‘Flash and Freeze’) of Identified Cortical Synapses in Acute Brain Slices.” <i>Neuron</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.neuron.2019.12.022\">https://doi.org/10.1016/j.neuron.2019.12.022</a>.","apa":"Borges Merjane, C., Kim, O., &#38; Jonas, P. M. (2020). Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2019.12.022\">https://doi.org/10.1016/j.neuron.2019.12.022</a>","short":"C. Borges Merjane, O. Kim, P.M. Jonas, Neuron 105 (2020) 992–1006.","ama":"Borges Merjane C, Kim O, Jonas PM. Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices. <i>Neuron</i>. 2020;105:992-1006. doi:<a href=\"https://doi.org/10.1016/j.neuron.2019.12.022\">10.1016/j.neuron.2019.12.022</a>","mla":"Borges Merjane, Carolina, et al. “Functional Electron Microscopy (‘Flash and Freeze’) of Identified Cortical Synapses in Acute Brain Slices.” <i>Neuron</i>, vol. 105, Elsevier, 2020, pp. 992–1006, doi:<a href=\"https://doi.org/10.1016/j.neuron.2019.12.022\">10.1016/j.neuron.2019.12.022</a>."},"department":[{"_id":"PeJo"}],"external_id":{"isi":["000520854700008"],"pmid":["31928842"]},"month":"03","oa":1,"has_accepted_license":"1","author":[{"orcid":"0000-0003-0005-401X","full_name":"Borges Merjane, Carolina","first_name":"Carolina","last_name":"Borges Merjane","id":"4305C450-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Olena","last_name":"Kim","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2344-1039","full_name":"Kim, Olena"},{"first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M"}],"intvolume":"       105","publication_identifier":{"issn":["0896-6273"]},"file_date_updated":"2020-11-20T08:58:53Z","date_updated":"2026-10-25T23:30:04Z","date_published":"2020-03-18T00:00:00Z","ddc":["570"],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","title":"Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices","language":[{"iso":"eng"}],"_id":"7473","pmid":1,"isi":1,"day":"18","file":[{"access_level":"open_access","content_type":"application/pdf","date_updated":"2020-11-20T08:58:53Z","date_created":"2020-11-20T08:58:53Z","relation":"main_file","success":1,"file_id":"8778","creator":"dernst","file_size":9712957,"checksum":"3582664addf26859e86ac5bec3e01416","file_name":"2020_Neuron_BorgesMerjane.pdf"}],"doi":"10.1016/j.neuron.2019.12.022","related_material":{"record":[{"id":"11196","status":"public","relation":"dissertation_contains"}],"link":[{"description":"News on IST Homepage","url":"https://ist.ac.at/en/news/flash-and-freeze-reveals-dynamics-of-nerve-connections/","relation":"press_release"}]},"acknowledgement":"This project has received funding from the European Research Council (ERC) and European Commission (EC), under the European Union’s Horizon 2020 research and innovation programme (ERC grant agreement No. 692692 and Marie Sklodowska-Curie 708497) and from Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27 Wittgenstein award and DK W1205-B09). We thank Johann Danzl and Ryuichi Shigemoto for critically reading the manuscript; Walter Kaufmann, Daniel Gutl, and Vanessa Zheden for extensive EM training, advice, and experimental assistance; Benjamin Suter for substantial help with light stimulation, ImageJ plugins for analysis, and manuscript editing; Florian Marr and Christina Altmutter for technical support; Eleftheria Kralli-Beller for manuscript editing; Julia König and Paul Wurzinger (Leica Microsystems) for helpful technical discussions; and Taija Makinen for providing the Prox1-CreERT2 mouse line.","quality_controlled":"1","article_processing_charge":"No","publication":"Neuron","project":[{"call_identifier":"H2020","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","name":"Presynaptic calcium channels distribution and impact on coupling at the hippocampal mossy fiber synapse","grant_number":"708497","_id":"25BAF7B2-B435-11E9-9278-68D0E5697425"},{"name":"Synaptic communication in neuronal microcircuits","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"_id":"25C3DBB6-B435-11E9-9278-68D0E5697425","grant_number":"W01205","name":"Zellkommunikation in Gesundheit und Krankheit","call_identifier":"FWF"}],"article_type":"original","abstract":[{"lang":"eng","text":"How structural and functional properties of synapses relate to each other is a fundamental question in neuroscience. Electrophysiology has elucidated mechanisms of synaptic transmission, and electron microscopy (EM) has provided insight into morphological properties of synapses. Here we describe an enhanced method for functional EM (“flash and freeze”), combining optogenetic stimulation with high-pressure freezing. We demonstrate that the improved method can be applied to intact networks in acute brain slices and organotypic slice cultures from mice. As a proof of concept, we probed vesicle pool changes during synaptic transmission at the hippocampal mossy fiber-CA3 pyramidal neuron synapse. Our findings show overlap of the docked vesicle pool and the functionally defined readily releasable pool and provide evidence of fast endocytosis at this synapse. Functional EM with acute slices and slice cultures has the potential to reveal the structural and functional mechanisms of transmission in intact, genetically perturbed, and disease-affected synapses."}],"publisher":"Elsevier","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png"},"scopus_import":"1","type":"journal_article","fulldoi":"https://doi.org/10.1016/j.neuron.2019.12.022","ec_funded":1,"volume":105,"page":"992-1006","corr_author":"1","oa_version":"Published Version","publication_status":"published"},{"citation":{"ama":"Kim O, Borges Merjane C, Jonas PM. Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy. In: <i>Intrinsic Activity</i>. Vol 7. Austrian Pharmacological Society; 2019. doi:<a href=\"https://doi.org/10.25006/ia.7.s1-a3.27\">10.25006/ia.7.s1-a3.27</a>","apa":"Kim, O., Borges Merjane, C., &#38; Jonas, P. M. (2019). Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy. In <i>Intrinsic Activity</i> (Vol. 7). Innsbruck, Austria: Austrian Pharmacological Society. <a href=\"https://doi.org/10.25006/ia.7.s1-a3.27\">https://doi.org/10.25006/ia.7.s1-a3.27</a>","short":"O. Kim, C. Borges Merjane, P.M. Jonas, in:, Intrinsic Activity, Austrian Pharmacological Society, 2019.","mla":"Kim, Olena, et al. “Functional Analysis of the Docked Vesicle Pool in Hippocampal Mossy Fiber Terminals by Electron Microscopy.” <i>Intrinsic Activity</i>, vol. 7, no. Suppl. 1, A3.27, Austrian Pharmacological Society, 2019, doi:<a href=\"https://doi.org/10.25006/ia.7.s1-a3.27\">10.25006/ia.7.s1-a3.27</a>.","ista":"Kim O, Borges Merjane C, Jonas PM. 2019. Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy. Intrinsic Activity. ANA: Austrian Neuroscience Association ; APHAR: Austrian Pharmacological Society vol. 7, A3.27.","chicago":"Kim, Olena, Carolina Borges Merjane, and Peter M Jonas. “Functional Analysis of the Docked Vesicle Pool in Hippocampal Mossy Fiber Terminals by Electron Microscopy.” In <i>Intrinsic Activity</i>, Vol. 7. Austrian Pharmacological Society, 2019. <a href=\"https://doi.org/10.25006/ia.7.s1-a3.27\">https://doi.org/10.25006/ia.7.s1-a3.27</a>.","ieee":"O. Kim, C. Borges Merjane, and P. M. Jonas, “Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy,” in <i>Intrinsic Activity</i>, Innsbruck, Austria, 2019, vol. 7, no. Suppl. 1."},"date_created":"2022-04-20T15:06:05Z","year":"2019","department":[{"_id":"PeJo"}],"status":"public","oa":1,"conference":{"location":"Innsbruck, Austria","name":"ANA: Austrian Neuroscience Association ; APHAR: Austrian Pharmacological Society","end_date":"2019-09-27","start_date":"2019-09-25"},"author":[{"last_name":"Kim","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","first_name":"Olena","full_name":"Kim, Olena","orcid":"0000-0003-2344-1039"},{"first_name":"Carolina","id":"4305C450-F248-11E8-B48F-1D18A9856A87","last_name":"Borges Merjane","orcid":"0000-0003-0005-401X","full_name":"Borges Merjane, Carolina"},{"full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","first_name":"Peter M"}],"month":"09","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_updated":"2026-10-25T23:30:04Z","date_published":"2019-09-11T00:00:00Z","ddc":["570"],"intvolume":"         7","publication_identifier":{"issn":["2309-8503"]},"language":[{"iso":"eng"}],"_id":"11222","day":"11","issue":"Suppl. 1","title":"Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy","keyword":["hippocampus","mossy fibers","readily releasable pool","electron microscopy"],"doi":"10.25006/ia.7.s1-a3.27","acknowledgement":"This work was supported by the ERC and EU Horizon 2020 (ERC 692692; MSC-IF 708497) and FWF Z 312-B27 Wittgenstein award; W 1205-B09).","related_material":{"record":[{"id":"11196","relation":"dissertation_contains","status":"public"}]},"project":[{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"_id":"25BAF7B2-B435-11E9-9278-68D0E5697425","grant_number":"708497","name":"Presynaptic calcium channels distribution and impact on coupling at the hippocampal mossy fiber synapse","call_identifier":"H2020"},{"call_identifier":"FWF","_id":"25C3DBB6-B435-11E9-9278-68D0E5697425","name":"Zellkommunikation in Gesundheit und Krankheit","grant_number":"W01205"},{"call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"Synaptic communication in neuronal microcircuits","grant_number":"Z00312"}],"publication":"Intrinsic Activity","quality_controlled":"1","article_processing_charge":"No","ec_funded":1,"fulldoi":"https://doi.org/10.25006/ia.7.s1-a3.27","type":"conference_abstract","publisher":"Austrian Pharmacological Society","main_file_link":[{"url":"https://www.intrinsicactivity.org/2019/7/S1/A3.27/","open_access":"1"}],"corr_author":"1","publication_status":"published","oa_version":"Published Version","article_number":"A3.27","volume":7},{"pubrep_id":"715","publication":"eLife","project":[{"call_identifier":"FP7","grant_number":"268548","name":"Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons","_id":"25C0F108-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"}],"abstract":[{"text":"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.","lang":"eng"}],"quality_controlled":"1","article_processing_charge":"No","doi":"10.7554/eLife.17977","file":[{"content_type":"application/pdf","access_level":"open_access","date_updated":"2020-07-14T12:44:44Z","date_created":"2018-12-12T10:17:05Z","relation":"main_file","file_name":"IST-2016-715-v1+1_e17977-download.pdf","checksum":"a7201280c571bed88ebd459ce5ce6a47","creator":"system","file_size":1477891,"file_id":"5257"}],"corr_author":"1","oa_version":"Published Version","publication_status":"published","volume":5,"article_number":"e17977","acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"PreCl"}],"type":"journal_article","ec_funded":1,"fulldoi":"https://doi.org/10.7554/eLife.17977","publisher":"eLife Sciences Publications","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"scopus_import":"1","has_accepted_license":"1","oa":1,"author":[{"full_name":"Vyleta, Nicholas","first_name":"Nicholas","last_name":"Vyleta","id":"36C4978E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Borges Merjane, Carolina","orcid":"0000-0003-0005-401X","first_name":"Carolina","id":"4305C450-F248-11E8-B48F-1D18A9856A87","last_name":"Borges Merjane"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","first_name":"Peter M","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804"}],"external_id":{"isi":["000387034600001"]},"month":"10","year":"2016","citation":{"ieee":"N. Vyleta, C. Borges Merjane, and P. M. Jonas, “Plasticity-dependent, full detonation at hippocampal mossy fiber–CA3 pyramidal neuron synapses,” <i>eLife</i>, vol. 5. eLife Sciences Publications, 2016.","chicago":"Vyleta, Nicholas, Carolina Borges Merjane, and Peter M Jonas. “Plasticity-Dependent, Full Detonation at Hippocampal Mossy Fiber–CA3 Pyramidal Neuron Synapses.” <i>ELife</i>. eLife Sciences Publications, 2016. <a href=\"https://doi.org/10.7554/eLife.17977\">https://doi.org/10.7554/eLife.17977</a>.","ista":"Vyleta N, Borges Merjane C, Jonas PM. 2016. Plasticity-dependent, full detonation at hippocampal mossy fiber–CA3 pyramidal neuron synapses. eLife. 5, e17977.","mla":"Vyleta, Nicholas, et al. “Plasticity-Dependent, Full Detonation at Hippocampal Mossy Fiber–CA3 Pyramidal Neuron Synapses.” <i>ELife</i>, vol. 5, e17977, eLife Sciences Publications, 2016, doi:<a href=\"https://doi.org/10.7554/eLife.17977\">10.7554/eLife.17977</a>.","apa":"Vyleta, N., Borges Merjane, C., &#38; Jonas, P. M. (2016). Plasticity-dependent, full detonation at hippocampal mossy fiber–CA3 pyramidal neuron synapses. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.17977\">https://doi.org/10.7554/eLife.17977</a>","short":"N. Vyleta, C. Borges Merjane, P.M. Jonas, ELife 5 (2016).","ama":"Vyleta N, Borges Merjane C, Jonas PM. Plasticity-dependent, full detonation at hippocampal mossy fiber–CA3 pyramidal neuron synapses. <i>eLife</i>. 2016;5. doi:<a href=\"https://doi.org/10.7554/eLife.17977\">10.7554/eLife.17977</a>"},"date_created":"2018-12-11T11:51:22Z","department":[{"_id":"PeJo"}],"status":"public","_id":"1323","language":[{"iso":"eng"}],"isi":1,"day":"25","title":"Plasticity-dependent, full detonation at hippocampal mossy fiber–CA3 pyramidal neuron synapses","publist_id":"5947","date_updated":"2025-09-22T08:26:29Z","ddc":["571","572"],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","date_published":"2016-10-25T00:00:00Z","intvolume":"         5","file_date_updated":"2020-07-14T12:44:44Z"}]