[{"year":"2026","keyword":["hypocampus","ca3 simulations","modelling"],"type":"software","citation":{"ieee":"A. Schlögl, “CA3Simu v1.06 (vargas2026v1).” Institute of Science and Technology Austria, 2026.","ama":"Schlögl A. CA3Simu v1.06 (vargas2026v1). 2026. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-21442\">10.15479/AT-ISTA-21442</a>","mla":"Schlögl, Alois. <i>CA3Simu v1.06 (Vargas2026v1)</i>. Institute of Science and Technology Austria, 2026, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-21442\">10.15479/AT-ISTA-21442</a>.","chicago":"Schlögl, Alois. “CA3Simu v1.06 (Vargas2026v1).” Institute of Science and Technology Austria, 2026. <a href=\"https://doi.org/10.15479/AT-ISTA-21442\">https://doi.org/10.15479/AT-ISTA-21442</a>.","ista":"Schlögl A. 2026. CA3Simu v1.06 (vargas2026v1), Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT-ISTA-21442\">10.15479/AT-ISTA-21442</a>.","short":"A. Schlögl, (2026).","apa":"Schlögl, A. (2026). CA3Simu v1.06 (vargas2026v1). Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-21442\">https://doi.org/10.15479/AT-ISTA-21442</a>"},"month":"03","file":[{"content_type":"application/gzip","date_updated":"2026-03-12T08:19:14Z","creator":"schloegl","relation":"main_file","access_level":"open_access","date_created":"2026-03-12T08:19:14Z","file_size":160410,"checksum":"441c8827717dcda05f91c127d15cf1e9","file_name":"ca3simu-vargas2026v1.tar.gz","file_id":"21443","success":1},{"creator":"schloegl","content_type":"text/markdown","date_updated":"2026-03-12T10:24:45Z","access_level":"open_access","relation":"main_file","file_size":10923,"date_created":"2026-03-12T10:24:45Z","checksum":"3c0092076228a15c0a7ae703192d43ea","file_name":"README.md","success":1,"file_id":"21445"}],"corr_author":"1","date_updated":"2026-03-12T11:28:52Z","oa":1,"status":"public","user_id":"68b8ca59-c5b3-11ee-8790-cd641c68093d","author":[{"last_name":"Schlögl","full_name":"Schlögl, Alois","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5621-8100","first_name":"Alois"}],"title":"CA3Simu v1.06 (vargas2026v1)","date_created":"2026-03-12T08:20:46Z","publisher":"Institute of Science and Technology Austria","project":[{"name":"Synaptic mechanisms of engram storage and retrieval in CA3 hippocampal microcircuits","_id":"e62b56fe-ab3c-11f0-94c7-d181dd352b3b","grant_number":"101199096"},{"name":"Mechanisms of GABA release in hippocampal circuits","grant_number":"P36232","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5"},{"grant_number":"PAT 4178023","_id":"8d9195e9-16d5-11f0-9cad-d075be887a1e","name":"Synaptic networks of human brain"},{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692"}],"doi":"10.15479/AT-ISTA-21442","file_date_updated":"2026-03-12T10:24:45Z","has_accepted_license":"1","tmp":{"name":"GNU General Public License 3.0","short":"GPL 3.0","legal_code_url":"https://www.gnu.org/licenses/gpl-3.0.en.html"},"date_published":"2026-03-12T00:00:00Z","department":[{"_id":"ScienComp"},{"_id":"PeJo"}],"day":"12","license":"https://opensource.org/licenses/GPL-3.0","ec_funded":1,"_id":"21442"},{"oa":1,"status":"public","ddc":["570"],"acknowledgement":"We thank Andrea Navas-Olive and Rebecca J. Morse-Mora for critically reading an earlier version of the manuscript. We also thank Florian Marr and Christina Altmutter for excellent technical assistance, Alois Schlögl for programming and data-handling assistance, Todor Asenov for technical support, and Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA. We are particularly grateful for assistance from the Imaging and Optics Facility, Preclinical Facility, Lab Support Facility, and Miba Machine Shop. The project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 692692 to P.J., Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 to J.F.W., and an ISTplus Fellowship through Marie Skłodowska-Curie grant agreement no. 754411 to V.V.-B.), the Austrian Science Fund (P 36232-B, PAT 4178023, and Cluster of Excellence 10.55776/COE16 to P.J.), and a CONACyT fellowship (289638 to V.V.-B.) and was supported by a non-stipendiary EMBO fellowship (ALTF 756–2020 to J.F.W.).","publication_status":"published","type":"journal_article","volume":44,"month":"08","file":[{"date_created":"2025-08-04T06:53:07Z","checksum":"556ff9760661ecd23949d75031043b1f","file_size":27695214,"file_name":"2025_CellReports_Watson.pdf","success":1,"file_id":"20106","creator":"dernst","content_type":"application/pdf","date_updated":"2025-08-04T06:53:07Z","access_level":"open_access","relation":"main_file"}],"corr_author":"1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"oa_version":"Published Version","article_number":"116080","publication":"Cell Reports","day":"01","ec_funded":1,"_id":"20099","publisher":"Elsevier","external_id":{"isi":["001544472300002"]},"project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"name":"Synaptic computations of the hippocampal CA3 circuitry","call_identifier":"H2020","grant_number":"101026635","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9"},{"grant_number":"P36232","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","name":"Mechanisms of GABA release in hippocampal circuits"},{"grant_number":"754411","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","name":"ISTplus - Postdoctoral Fellowships"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"has_accepted_license":"1","date_updated":"2025-09-30T14:12:02Z","isi":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","author":[{"full_name":"Watson, Jake","last_name":"Watson","first_name":"Jake","orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"full_name":"Vargas Barroso, Victor M","last_name":"Vargas Barroso","first_name":"Victor M","id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Jonas","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","first_name":"Peter M"}],"title":"Cell-specific wiring routes information flow through hippocampal CA3","OA_place":"publisher","year":"2025","citation":{"ieee":"J. Watson, V. M. Vargas Barroso, and P. M. Jonas, “Cell-specific wiring routes information flow through hippocampal CA3,” <i>Cell Reports</i>, vol. 44, no. 8. Elsevier, 2025.","ama":"Watson J, Vargas Barroso VM, Jonas PM. Cell-specific wiring routes information flow through hippocampal CA3. <i>Cell Reports</i>. 2025;44(8). doi:<a href=\"https://doi.org/10.1016/j.celrep.2025.116080\">10.1016/j.celrep.2025.116080</a>","apa":"Watson, J., Vargas Barroso, V. M., &#38; Jonas, P. M. (2025). Cell-specific wiring routes information flow through hippocampal CA3. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2025.116080\">https://doi.org/10.1016/j.celrep.2025.116080</a>","mla":"Watson, Jake, et al. “Cell-Specific Wiring Routes Information Flow through Hippocampal CA3.” <i>Cell Reports</i>, vol. 44, no. 8, 116080, Elsevier, 2025, doi:<a href=\"https://doi.org/10.1016/j.celrep.2025.116080\">10.1016/j.celrep.2025.116080</a>.","short":"J. Watson, V.M. Vargas Barroso, P.M. Jonas, Cell Reports 44 (2025).","ista":"Watson J, Vargas Barroso VM, Jonas PM. 2025. Cell-specific wiring routes information flow through hippocampal CA3. Cell Reports. 44(8), 116080.","chicago":"Watson, Jake, Victor M Vargas Barroso, and Peter M Jonas. “Cell-Specific Wiring Routes Information Flow through Hippocampal CA3.” <i>Cell Reports</i>. Elsevier, 2025. <a href=\"https://doi.org/10.1016/j.celrep.2025.116080\">https://doi.org/10.1016/j.celrep.2025.116080</a>."},"publication_identifier":{"issn":["2639-1856"],"eissn":["2211-1247"]},"language":[{"iso":"eng"}],"DOAJ_listed":"1","article_processing_charge":"Yes","date_published":"2025-08-01T00:00:00Z","abstract":[{"text":"The hippocampus, critical for learning and memory, is dogmatically described as a trisynaptic circuit where dentate gyrus granule cells (GCs), CA3 pyramidal neurons (PNs), and CA1 PNs are serially connected. However, CA3 also forms an autoassociative network, and its PNs have diverse morphologies, intrinsic properties, and GC input levels. How PN subtypes compose this recurrent network is unknown. To determine the synaptic arrangement of identified CA3 PNs, we combine multicellular patch-clamp recording and post hoc morphological analysis in mouse hippocampal slices. PNs can be divided into distinct “superficial” and “deep” subclasses, the latter including previously reported “athorny” cells. Subclasses have distinct input-output transformations and asymmetric connectivity, which is more abundant from superficial to deep PNs, splitting CA3 locally into two parallel recurrent networks. Coincident spontaneous inhibition occurs frequently within but not between subclasses, implying subclass-specific inhibitory innervation. Our results suggest two separately controlled sublayers for parallel information processing in hippocampal CA3.","lang":"eng"}],"department":[{"_id":"PeJo"}],"license":"https://creativecommons.org/licenses/by/4.0/","date_created":"2025-08-03T22:01:30Z","OA_type":"gold","intvolume":"        44","PlanS_conform":"1","doi":"10.1016/j.celrep.2025.116080","issue":"8","article_type":"original","file_date_updated":"2025-08-04T06:53:07Z","scopus_import":"1","quality_controlled":"1"},{"volume":603,"corr_author":"1","file":[{"success":1,"file_id":"20949","file_size":10875254,"checksum":"3326e49795f44a7c51c16ecbcce58cde","date_created":"2026-01-05T13:13:06Z","file_name":"2025_JourPhysiology_Greger.pdf","access_level":"open_access","relation":"main_file","creator":"dernst","content_type":"application/pdf","date_updated":"2026-01-05T13:13:06Z"}],"month":"11","publication_status":"published","type":"journal_article","acknowledgement":"This work was supported by Biological Services teams at both the Laboratory of Molecular Biology and Ares facilities. The authors are very grateful to Prof. Helmut Kessels and Dr. Hinze Ho for initial discussions that led to this study, Dr. Andrew Penn for constructive feedback on the project, Xinyao Dou for comments on the study, and Profs. Peter Jonas and Roger Nicoll for feedback on the manuscript. Funding was provided by the Medical Research Council (MRC – MC_U105174197 to I.H.G.) and the European Union's Horizon 2020 programme through a Marie Skłodowska-Curie Actions Individual Fellowship (MSCA-IF 101026635 to J.F.W.).","page":"7189-7205","status":"public","ddc":["570"],"oa":1,"has_accepted_license":"1","project":[{"name":"Synaptic computations of the hippocampal CA3 circuitry","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","grant_number":"101026635","call_identifier":"H2020"}],"external_id":{"pmid":["41015537"],"isi":["001581924700001"]},"publisher":"Wiley","day":"15","publication":"Journal of Physiology","_id":"20457","ec_funded":1,"oa_version":"Published Version","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"pmid":1,"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1469-7793"],"issn":["0022-3751"]},"article_processing_charge":"Yes (in subscription journal)","year":"2025","citation":{"ieee":"I. H. Greger and J. Watson, “‘Mini analysis’ misrepresents changes in synaptic properties due to incomplete event detection,” <i>Journal of Physiology</i>, vol. 603, no. 22. Wiley, pp. 7189–7205, 2025.","ama":"Greger IH, Watson J. ‘Mini analysis’ misrepresents changes in synaptic properties due to incomplete event detection. <i>Journal of Physiology</i>. 2025;603(22):7189-7205. doi:<a href=\"https://doi.org/10.1113/JP288183\">10.1113/JP288183</a>","apa":"Greger, I. H., &#38; Watson, J. (2025). ‘Mini analysis’ misrepresents changes in synaptic properties due to incomplete event detection. <i>Journal of Physiology</i>. Wiley. <a href=\"https://doi.org/10.1113/JP288183\">https://doi.org/10.1113/JP288183</a>","mla":"Greger, Ingo H., and Jake Watson. “‘Mini Analysis’ Misrepresents Changes in Synaptic Properties Due to Incomplete Event Detection.” <i>Journal of Physiology</i>, vol. 603, no. 22, Wiley, 2025, pp. 7189–205, doi:<a href=\"https://doi.org/10.1113/JP288183\">10.1113/JP288183</a>.","chicago":"Greger, Ingo H., and Jake Watson. “‘Mini Analysis’ Misrepresents Changes in Synaptic Properties Due to Incomplete Event Detection.” <i>Journal of Physiology</i>. Wiley, 2025. <a href=\"https://doi.org/10.1113/JP288183\">https://doi.org/10.1113/JP288183</a>.","ista":"Greger IH, Watson J. 2025. ‘Mini analysis’ misrepresents changes in synaptic properties due to incomplete event detection. Journal of Physiology. 603(22), 7189–7205.","short":"I.H. Greger, J. Watson, Journal of Physiology 603 (2025) 7189–7205."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"‘Mini analysis’ misrepresents changes in synaptic properties due to incomplete event detection","author":[{"first_name":"Ingo H.","full_name":"Greger, Ingo H.","last_name":"Greger"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake","orcid":"0000-0002-8698-3823","last_name":"Watson","full_name":"Watson, Jake"}],"OA_place":"publisher","date_updated":"2026-01-05T13:13:32Z","isi":1,"related_material":{"link":[{"url":"https://github.com/jakefwatson/miniplace","relation":"software"}]},"file_date_updated":"2026-01-05T13:13:06Z","article_type":"original","issue":"22","quality_controlled":"1","scopus_import":"1","intvolume":"       603","date_created":"2025-10-12T22:01:27Z","OA_type":"hybrid","doi":"10.1113/JP288183","PlanS_conform":"1","department":[{"_id":"PeJo"}],"date_published":"2025-11-15T00:00:00Z","abstract":[{"text":"Patch-clamp recording of miniature postsynaptic currents (mPSCs, or ‘minis’) is used extensively to investigate the functional properties of synapses. With this approach, spontaneous synaptic transmission events are recorded in an attempt to determine quantal synaptic parameters or the effect of synaptic manipulations. However, at the majority of brain synapses these events are small, with many undetectable due to recording noise. The effects of incomplete detection were well appreciated in the early years of synaptic physiology analysis, but appear to be increasingly forgotten. Here we sought to characterise the consequences of incomplete detection on the interpretability of mini analysis, using simulated mPSC data to give full control over event parameters. We demonstrate that commonly reported measures such as mean event amplitude and frequency, are misrepresented by the loss of undetected events. Probabilistic loss of small events results in detected event amplitude distributions that appear biologically complete, yet do not reflect the underlying synaptic properties. With both simulated and experimental datasets, we demonstrate that specific changes in event amplitude are primarily detected as changes in frequency, compromising classical biological interpretations. To facilitate more robust data analysis and interpretation, we detail a means for experimental estimation of the event detection limit and provide practical recommendations for data analysis. Together, our study highlights how mini analysis is prone to falsely reporting synaptic changes, raising awareness of these considerations, and provides a framework for more robust data analysis and interpretation.","lang":"eng"}]},{"date_updated":"2025-12-01T15:04:34Z","isi":1,"author":[{"first_name":"Katharina","orcid":"0000-0002-1485-0351","id":"39302e62-fcfc-11ec-8196-8b01447dbd3d","full_name":"Lichter, Katharina","last_name":"Lichter"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Kiss, shrink, run","citation":{"ista":"Lichter K. 2025. Kiss, shrink, run. Science. 390(6770), 236–237.","chicago":"Lichter, Katharina. “Kiss, Shrink, Run.” <i>Science</i>. AAAS, 2025. <a href=\"https://doi.org/10.1126/science.aec0091\">https://doi.org/10.1126/science.aec0091</a>.","short":"K. Lichter, Science 390 (2025) 236–237.","mla":"Lichter, Katharina. “Kiss, Shrink, Run.” <i>Science</i>, vol. 390, no. 6770, AAAS, 2025, pp. 236–37, doi:<a href=\"https://doi.org/10.1126/science.aec0091\">10.1126/science.aec0091</a>.","apa":"Lichter, K. (2025). Kiss, shrink, run. <i>Science</i>. AAAS. <a href=\"https://doi.org/10.1126/science.aec0091\">https://doi.org/10.1126/science.aec0091</a>","ama":"Lichter K. Kiss, shrink, run. <i>Science</i>. 2025;390(6770):236-237. doi:<a href=\"https://doi.org/10.1126/science.aec0091\">10.1126/science.aec0091</a>","ieee":"K. Lichter, “Kiss, shrink, run,” <i>Science</i>, vol. 390, no. 6770. AAAS, pp. 236–237, 2025."},"year":"2025","article_processing_charge":"No","language":[{"iso":"eng"}],"publication_identifier":{"issn":["0036-8075"],"eissn":["1095-9203"]},"abstract":[{"text":"A unified mechanism directs synaptic vesicle release","lang":"eng"}],"date_published":"2025-10-16T00:00:00Z","department":[{"_id":"PeJo"}],"doi":"10.1126/science.aec0091","intvolume":"       390","date_created":"2025-10-26T23:01:34Z","OA_type":"closed access","quality_controlled":"1","scopus_import":"1","article_type":"comment","issue":"6770","status":"public","page":"236-237","acknowledgement":"The author thanks P. Jonas for feedback on the manuscript and acknowledges support from the European Union’s Horizon 2020 research and innovation program under Marie Skłodowska-Curie grant agreement no. 101034413.","publication_status":"published","type":"journal_article","corr_author":"1","month":"10","volume":390,"pmid":1,"oa_version":"None","ec_funded":1,"_id":"20532","publication":"Science","day":"16","project":[{"name":"IST-BRIDGE: International postdoctoral program","grant_number":"101034413","call_identifier":"H2020","_id":"fc2ed2f7-9c52-11eb-aca3-c01059dda49c"}],"external_id":{"pmid":["41100630"],"isi":["001610669900024"]},"publisher":"AAAS"},{"date_updated":"2026-01-12T09:31:56Z","title":"Spatiotemporal patterns differentiate hippocampal sharp-wave ripples from interictal epileptiform discharges in mice and humans","author":[{"last_name":"Maslarova","full_name":"Maslarova, Anna","first_name":"Anna"},{"first_name":"Jiyun N.","full_name":"Shin, Jiyun N.","last_name":"Shin"},{"id":"739d26c9-52e8-11ee-8d72-f14d3893b4ce","orcid":"0000-0002-9280-8597","first_name":"Andrea C","last_name":"Navas Olivé","full_name":"Navas Olivé, Andrea C"},{"first_name":"Mihály","full_name":"Vöröslakos, Mihály","last_name":"Vöröslakos"},{"first_name":"Hajo","last_name":"Hamer","full_name":"Hamer, Hajo"},{"first_name":"Arnd","last_name":"Doerfler","full_name":"Doerfler, Arnd"},{"first_name":"Simon","last_name":"Henin","full_name":"Henin, Simon"},{"last_name":"Buzsáki","full_name":"Buzsáki, György","first_name":"György"},{"first_name":"Anli","full_name":"Liu, Anli","last_name":"Liu"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","OA_place":"publisher","year":"2025","citation":{"ama":"Maslarova A, Shin JN, Navas Olivé AC, et al. Spatiotemporal patterns differentiate hippocampal sharp-wave ripples from interictal epileptiform discharges in mice and humans. <i>Nature Communications</i>. 2025;16. doi:<a href=\"https://doi.org/10.1038/s41467-025-66562-6\">10.1038/s41467-025-66562-6</a>","ieee":"A. Maslarova <i>et al.</i>, “Spatiotemporal patterns differentiate hippocampal sharp-wave ripples from interictal epileptiform discharges in mice and humans,” <i>Nature Communications</i>, vol. 16. Springer Nature, 2025.","apa":"Maslarova, A., Shin, J. N., Navas Olivé, A. C., Vöröslakos, M., Hamer, H., Doerfler, A., … Liu, A. (2025). Spatiotemporal patterns differentiate hippocampal sharp-wave ripples from interictal epileptiform discharges in mice and humans. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-025-66562-6\">https://doi.org/10.1038/s41467-025-66562-6</a>","ista":"Maslarova A, Shin JN, Navas Olivé AC, Vöröslakos M, Hamer H, Doerfler A, Henin S, Buzsáki G, Liu A. 2025. Spatiotemporal patterns differentiate hippocampal sharp-wave ripples from interictal epileptiform discharges in mice and humans. Nature Communications. 16, 11636.","short":"A. Maslarova, J.N. Shin, A.C. Navas Olivé, M. Vöröslakos, H. Hamer, A. Doerfler, S. Henin, G. Buzsáki, A. Liu, Nature Communications 16 (2025).","chicago":"Maslarova, Anna, Jiyun N. Shin, Andrea C Navas Olivé, Mihály Vöröslakos, Hajo Hamer, Arnd Doerfler, Simon Henin, György Buzsáki, and Anli Liu. “Spatiotemporal Patterns Differentiate Hippocampal Sharp-Wave Ripples from Interictal Epileptiform Discharges in Mice and Humans.” <i>Nature Communications</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1038/s41467-025-66562-6\">https://doi.org/10.1038/s41467-025-66562-6</a>.","mla":"Maslarova, Anna, et al. “Spatiotemporal Patterns Differentiate Hippocampal Sharp-Wave Ripples from Interictal Epileptiform Discharges in Mice and Humans.” <i>Nature Communications</i>, vol. 16, 11636, Springer Nature, 2025, doi:<a href=\"https://doi.org/10.1038/s41467-025-66562-6\">10.1038/s41467-025-66562-6</a>."},"publication_identifier":{"eissn":["2041-1723"]},"language":[{"iso":"eng"}],"DOAJ_listed":"1","article_processing_charge":"Yes","date_published":"2025-12-30T00:00:00Z","abstract":[{"text":"Hippocampal sharp-wave ripples (SPW-Rs) are high-frequency oscillations critical for memory consolidation. Despite extensive characterization in rodents, their detection in humans is limited by coarse spatial sampling, interictal epileptiform discharges (IEDs), and a lack of consensus on human ripple localization and morphology. Here, we demonstrate that mouse and human hippocampal ripples share spatial, spectral and temporal features, which are clearly distinct from IEDs. In recordings from male APP/PS1 mice, SPW-Rs were distinguishable from IEDs by multiple criteria. Hippocampal ripples recorded during NREM sleep in female and male surgical epilepsy patients exhibited similar narrowband frequency peaks and multiple ripple cycles in the CA1 and subiculum regions. Conversely, IEDs showed a broad spatial extent and wide-band frequency power. We developed a semi-automated, ripple curation toolbox (ripmap) to separate event waveforms by low-dimensional embedding to reduce false-positive rate in selected ripple channels. Our approach improves ripple detection and provides a firm foundation for future human memory research.","lang":"eng"}],"department":[{"_id":"PeJo"}],"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","date_created":"2026-01-11T23:01:35Z","OA_type":"gold","intvolume":"        16","doi":"10.1038/s41467-025-66562-6","article_type":"original","file_date_updated":"2026-01-12T09:30:15Z","scopus_import":"1","quality_controlled":"1","ddc":["570"],"status":"public","oa":1,"acknowledgement":"We thank Karl Rössler and Sebastian Brandner for the human SEEG implantations; Katja Kobow for providing the histopathological findings of the patients; Jay Jeschke for help with human electrode localization; Esha Brahmbhatt and Deren Aykan for help with animal habituation; Mursel Karadas for the rodent treadmill design; Nicholas Paleologos, Noam Nitzan, Michael D Hadler and Samuel McKenzie for rating events in a human ripple survey included in a previous version of the manuscript; Nicholas Paleologos for sharing NYU iEEG data for validating UMAP parameters; Julio Esparza for help on the topological analysis through discussions; Thomas Hainmüller, Yiyao Zhang and Mursel Karadas for feedback on the manuscript. We would like to acknowledge Corticale SRL (Genoa, Italy) for providing the SiNAPS probes, and NeuroNexus (Ann Arbor, MI) for their contribution of the data acquisition system and Radiens software. We further acknowledge both Corticale and NeuroNexus for training and support making this research possible. This work was supported by the German Research Foundation (DFG; Walter Benjamin Fellowship MA 10301/1-1, A.M.), NYU Langone Health Finding a Cure for Epilepsy and Seizures (FACES, A.M.), the NOMIS Fellowship (A.N.-O.), the National Institutes of Health (R01NS127954, K23NS104252, A.L.; MH122391, U19NS107616, R01MH139216 G.B.,), and the NYU Department of Neurology (A.L.).","publication_status":"published","type":"journal_article","volume":16,"month":"12","file":[{"file_name":"2025_NatureComm_Maslarova.pdf","file_size":7629997,"date_created":"2026-01-12T09:30:15Z","checksum":"a8a1670e197484382e087be60f643945","success":1,"file_id":"20978","creator":"dernst","date_updated":"2026-01-12T09:30:15Z","content_type":"application/pdf","access_level":"open_access","relation":"main_file"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"oa_version":"Published Version","pmid":1,"article_number":"11636","day":"30","publication":"Nature Communications","_id":"20977","publisher":"Springer Nature","project":[{"_id":"9B861AAC-BA93-11EA-9121-9846C619BF3A","name":"NOMIS Fellowship Program"}],"external_id":{"pmid":["39975118"]},"has_accepted_license":"1"},{"author":[{"last_name":"Watson","full_name":"Watson, Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake","orcid":"0000-0002-8698-3823"},{"id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87","first_name":"Victor M","last_name":"Vargas Barroso","full_name":"Vargas Barroso, Victor M"},{"first_name":"Rebecca","id":"ceb89ae7-dc8d-11ea-abe3-da3301d0eab4","full_name":"Morse, Rebecca","last_name":"Morse"},{"orcid":"0000-0002-9280-8597","first_name":"Andrea C","id":"739d26c9-52e8-11ee-8d72-f14d3893b4ce","full_name":"Navas Olivé, Andrea C","last_name":"Navas Olivé"},{"id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","first_name":"Mojtaba","orcid":"0000-0002-7667-6854","last_name":"Tavakoli","full_name":"Tavakoli, Mojtaba"},{"full_name":"Danzl, Johann G","last_name":"Danzl","orcid":"0000-0001-8559-3973","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Tomschik","full_name":"Tomschik, Matthias","first_name":"Matthias"},{"full_name":"Rössler, Karl","last_name":"Rössler","first_name":"Karl"},{"orcid":"0000-0001-5001-4804","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","last_name":"Jonas"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory","OA_place":"publisher","date_updated":"2026-04-14T08:34:32Z","isi":1,"related_material":{"record":[{"id":"18688","relation":"earlier_version","status":"public"}]},"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1097-4172"],"issn":["0092-8674"]},"article_processing_charge":"Yes (via OA deal)","year":"2025","citation":{"ieee":"J. Watson <i>et al.</i>, “Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory,” <i>Cell</i>, vol. 188, no. 2. Elsevier, p. 501–514.e18, 2025.","ama":"Watson J, Vargas Barroso VM, Morse R, et al. Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory. <i>Cell</i>. 2025;188(2):501-514.e18. doi:<a href=\"https://doi.org/10.1016/j.cell.2024.11.022\">10.1016/j.cell.2024.11.022</a>","apa":"Watson, J., Vargas Barroso, V. M., Morse, R., Navas Olivé, A. C., Tavakoli, M., Danzl, J. G., … Jonas, P. M. (2025). Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory. <i>Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cell.2024.11.022\">https://doi.org/10.1016/j.cell.2024.11.022</a>","mla":"Watson, Jake, et al. “Human Hippocampal CA3 Uses Specific Functional Connectivity Rules for Efficient Associative Memory.” <i>Cell</i>, vol. 188, no. 2, Elsevier, 2025, p. 501–514.e18, doi:<a href=\"https://doi.org/10.1016/j.cell.2024.11.022\">10.1016/j.cell.2024.11.022</a>.","chicago":"Watson, Jake, Victor M Vargas Barroso, Rebecca Morse, Andrea C Navas Olivé, Mojtaba Tavakoli, Johann G Danzl, Matthias Tomschik, Karl Rössler, and Peter M Jonas. “Human Hippocampal CA3 Uses Specific Functional Connectivity Rules for Efficient Associative Memory.” <i>Cell</i>. Elsevier, 2025. <a href=\"https://doi.org/10.1016/j.cell.2024.11.022\">https://doi.org/10.1016/j.cell.2024.11.022</a>.","short":"J. Watson, V.M. Vargas Barroso, R. Morse, A.C. Navas Olivé, M. Tavakoli, J.G. Danzl, M. Tomschik, K. Rössler, P.M. Jonas, Cell 188 (2025) 501–514.e18.","ista":"Watson J, Vargas Barroso VM, Morse R, Navas Olivé AC, Tavakoli M, Danzl JG, Tomschik M, Rössler K, Jonas PM. 2025. Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory. Cell. 188(2), 501–514.e18."},"department":[{"_id":"JoDa"},{"_id":"PeJo"},{"_id":"GradSch"}],"date_published":"2025-01-23T00:00:00Z","abstract":[{"lang":"eng","text":"Our brain has remarkable computational power, generating sophisticated behaviors, storing memories over an individual’s lifetime, and producing higher cognitive functions. However, little of our neuroscience knowledge covers the human brain. Is this organ truly unique, or is it a scaled version of the extensively studied rodent brain? Combining multicellular patch-clamp recording with expansion-based superresolution microscopy and full-scale modeling, we determined the cellular and microcircuit properties of the human hippocampal CA3 region, a fundamental circuit for memory storage. In contrast to neocortical networks, human hippocampal CA3 displayed sparse connectivity, providing a circuit architecture that maximizes associational power. Human synapses showed unique reliability, high precision, and long integration times, exhibiting both species- and circuit-specific properties. Together with expanded neuronal numbers, these circuit characteristics greatly enhanced the memory storage capacity of CA3. Our results reveal distinct microcircuit properties of the human hippocampus and begin to unravel the inner workings of our most complex organ. "}],"file_date_updated":"2025-01-27T08:46:33Z","article_type":"original","issue":"2","quality_controlled":"1","scopus_import":"1","intvolume":"       188","OA_type":"hybrid","date_created":"2025-01-26T23:01:49Z","doi":"10.1016/j.cell.2024.11.022","acknowledgement":"We thank Florian Marr for excellent technical assistance, Christina Altmutter and Julia Flor for technical support, Alois Schlögl for programming, Todor Asenov for development of the transportation box for human brain tissue, Tim Vogels for guidance on simulations, Marcus Huber for mathematical advice, Walter Kaufmann for assistance with handling frozen tissue, and Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA, and we are grateful for assistance from Christoph Sommer and the Imaging and Optics Facility, Preclinical Facility, Lab Support Facility, Miba Machine Shop, and Scientific Computing. We are particularly grateful to the patient donors for their support of this project and also acknowledge the excellent support of the Medical University of Vienna Department of Neurosurgery staff; Romana Hoeftberger and the Division of Neuropathology and Neurochemistry; Gregor Kasprian and the Division of Neuroradiology and Musculoskeletal Radiology; and Christoph Baumgartner, Martha Feucht, and Ekaterina Pataraia for their clinical care of the patients included in this study. We thank Laura Jonkman, the NABCA biobank, and postmortem brain sample donors for their support of this research. The project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (advanced grant no. 692692 to P.J. and Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 to J.F.W.), the Austrian Science Fund (FWF; grant PAT 4178023 to P.J. and grant DK W1232 to M.R.T. and J.G.D.), the Austrian Academy of Sciences (DOC fellowship 26137 to M.R.T.), and a NOMIS-ISTA fellowship (to A.N.-O.).","page":"501-514.e18","oa":1,"ddc":["570"],"status":"public","volume":188,"corr_author":"1","month":"01","file":[{"date_created":"2025-01-27T08:46:33Z","file_size":14082343,"checksum":"d5a818edc32d249cdf75e1bb5b70a4b7","file_name":"2025_Cell_Watson.pdf","success":1,"file_id":"18884","creator":"dernst","content_type":"application/pdf","date_updated":"2025-01-27T08:46:33Z","access_level":"open_access","relation":"main_file"}],"publication_status":"published","type":"journal_article","day":"23","publication":"Cell","_id":"18879","ec_funded":1,"oa_version":"Published Version","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"pmid":1,"has_accepted_license":"1","project":[{"call_identifier":"H2020","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"name":"Synaptic computations of the hippocampal CA3 circuitry","call_identifier":"H2020","grant_number":"101026635","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9"},{"name":"Studying Organelle Structure and Function at Nanoscale Resolution with Expansion Microscopy","_id":"6285a163-2b32-11ec-9570-8e204ca2dba5","grant_number":"26137"},{"call_identifier":"FWF","grant_number":"W1232","_id":"2548AE96-B435-11E9-9278-68D0E5697425","name":"Molecular Drug Targets"},{"grant_number":"PAT 4178023","_id":"8d9195e9-16d5-11f0-9cad-d075be887a1e","name":"Synaptic networks of human brain"},{"name":"NOMIS Fellowship Program","_id":"9B861AAC-BA93-11EA-9121-9846C619BF3A"}],"external_id":{"pmid":["39667938"],"isi":["001408395600001"]},"publisher":"Elsevier","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"ScienComp"}]},{"publisher":"CRC Press","date_created":"2024-09-11T10:40:36Z","place":"Boca Raton","doi":"10.1201/9781003055211-8","edition":"1","quality_controlled":"1","scopus_import":"1","oa_version":"None","date_published":"2024-09-05T00:00:00Z","abstract":[{"lang":"eng","text":"DNA cloning is a core technique in biomedical and biotechnological research and is used to assemble and modify DNA fragments at will. While DNA cloning has traditionally relied on restriction enzymes, recent homology-based methods offer improved protocols together with seamless and directional assembly of desired products, overcoming the main disadvantages of restriction enzyme DNA cloning. This chapter provides a historical perspective on DNA cloning, presents a detailed discussion on state-of-the-art in vitro and in vivo homology-based methodologies, covering the basics of how to perform all major plasmid modifications (sub-cloning, site-directed mutagenesis, insertions, and deletions), and gives examples of how to apply these techniques for complex DNA cloning projects."}],"department":[{"_id":"PeJo"}],"publication":"Handbook of Molecular Biotechnology","day":"05","_id":"18058","year":"2024","type":"book_chapter","publication_status":"published","citation":{"ista":"Watson J, Arroyo-Urea S, García-Nafría J. 2024.DNA Cloning. In: Handbook of Molecular Biotechnology. , 66–72.","short":"J. Watson, S. Arroyo-Urea, J. García-Nafría, in:, D. Liu (Ed.), Handbook of Molecular Biotechnology, 1st ed., CRC Press, Boca Raton, 2024, pp. 66–72.","chicago":"Watson, Jake, Sandra Arroyo-Urea, and Javier García-Nafría. “DNA Cloning.” In <i>Handbook of Molecular Biotechnology</i>, edited by Dongyou Liu, 1st ed., 66–72. Boca Raton: CRC Press, 2024. <a href=\"https://doi.org/10.1201/9781003055211-8\">https://doi.org/10.1201/9781003055211-8</a>.","mla":"Watson, Jake, et al. “DNA Cloning.” <i>Handbook of Molecular Biotechnology</i>, edited by Dongyou Liu, 1st ed., CRC Press, 2024, pp. 66–72, doi:<a href=\"https://doi.org/10.1201/9781003055211-8\">10.1201/9781003055211-8</a>.","apa":"Watson, J., Arroyo-Urea, S., &#38; García-Nafría, J. (2024). DNA Cloning. In D. Liu (Ed.), <i>Handbook of Molecular Biotechnology</i> (1st ed., pp. 66–72). Boca Raton: CRC Press. <a href=\"https://doi.org/10.1201/9781003055211-8\">https://doi.org/10.1201/9781003055211-8</a>","ama":"Watson J, Arroyo-Urea S, García-Nafría J. DNA Cloning. In: Liu D, ed. <i>Handbook of Molecular Biotechnology</i>. 1st ed. Boca Raton: CRC Press; 2024:66-72. doi:<a href=\"https://doi.org/10.1201/9781003055211-8\">10.1201/9781003055211-8</a>","ieee":"J. Watson, S. Arroyo-Urea, and J. García-Nafría, “DNA Cloning,” in <i>Handbook of Molecular Biotechnology</i>, 1st ed., D. Liu, Ed. Boca Raton: CRC Press, 2024, pp. 66–72."},"publication_identifier":{"eisbn":["9781003055211"]},"language":[{"iso":"eng"}],"month":"09","article_processing_charge":"No","date_updated":"2024-09-11T11:16:58Z","status":"public","editor":[{"last_name":"Liu","full_name":"Liu, Dongyou","first_name":"Dongyou"}],"title":"DNA Cloning","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823","first_name":"Jake","last_name":"Watson","full_name":"Watson, Jake"},{"last_name":"Arroyo-Urea","full_name":"Arroyo-Urea, Sandra","first_name":"Sandra"},{"first_name":"Javier","full_name":"García-Nafría, Javier","last_name":"García-Nafría"}],"page":"66-72"},{"status":"public","acknowledgement":"We thank previous students, postdocs, and collaborators, particularly J. Geiger, and (in alphabetical order) H. Alle, J. Bischofberger, C. Borges-Merjane, D. Engel, M. Frotscher, S. Hallermann, M. Heckmann, S. Jamrichova, O. Kim, L. Li, K. Lichter, P. Lin, J. Lübke, Y. Okamoto, C. Pawlu, C. Schmidt-Hieber, N. Spruston, and N. Vyleta for their outstanding experimental contributions. We also thank P. Castillo, J. Geiger, T. Sakaba, S. Siegert, T. Vogels, and J. Watson for critically reading the manuscript, E. Kralli-Beller for text editing, and J. Malikovic and L. Slomianka for useful discussions. We apologize that, due to space constraints, not all relevant papers could be cited.\r\nThis project was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement 692692, AdG “GIANTSYN”) and the Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein Award; P 36232-B, stand-alone grant), both to P.J.","page":"eadg6757","type":"journal_article","publication_status":"published","volume":383,"month":"03","corr_author":"1","oa_version":"None","pmid":1,"publication":"Science","day":"08","_id":"15117","ec_funded":1,"publisher":"AAAS","external_id":{"isi":["001216996700015"],"pmid":["38452088"]},"project":[{"grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"name":"Synaptic communication in neuronal microcircuits","call_identifier":"FWF","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"name":"Mechanisms of GABA release in hippocampal circuits","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","grant_number":"P36232"}],"date_updated":"2025-09-04T13:04:34Z","isi":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","author":[{"id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","first_name":"David H","orcid":"0000-0001-7577-1676","last_name":"Vandael","full_name":"Vandael, David H"},{"first_name":"Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","last_name":"Jonas"}],"title":"Structure, biophysics, and circuit function of a \"giant\" cortical presynaptic terminal","year":"2024","citation":{"ama":"Vandael DH, Jonas PM. Structure, biophysics, and circuit function of a “giant” cortical presynaptic terminal. <i>Science</i>. 2024;383(6687):eadg6757. doi:<a href=\"https://doi.org/10.1126/science.adg6757\">10.1126/science.adg6757</a>","ieee":"D. H. Vandael and P. M. Jonas, “Structure, biophysics, and circuit function of a ‘giant’ cortical presynaptic terminal,” <i>Science</i>, vol. 383, no. 6687. AAAS, p. eadg6757, 2024.","short":"D.H. Vandael, P.M. Jonas, Science 383 (2024) eadg6757.","chicago":"Vandael, David H, and Peter M Jonas. “Structure, Biophysics, and Circuit Function of a ‘Giant’ Cortical Presynaptic Terminal.” <i>Science</i>. AAAS, 2024. <a href=\"https://doi.org/10.1126/science.adg6757\">https://doi.org/10.1126/science.adg6757</a>.","ista":"Vandael DH, Jonas PM. 2024. Structure, biophysics, and circuit function of a ‘giant’ cortical presynaptic terminal. Science. 383(6687), eadg6757.","mla":"Vandael, David H., and Peter M. Jonas. “Structure, Biophysics, and Circuit Function of a ‘Giant’ Cortical Presynaptic Terminal.” <i>Science</i>, vol. 383, no. 6687, AAAS, 2024, p. eadg6757, doi:<a href=\"https://doi.org/10.1126/science.adg6757\">10.1126/science.adg6757</a>.","apa":"Vandael, D. H., &#38; Jonas, P. M. (2024). Structure, biophysics, and circuit function of a “giant” cortical presynaptic terminal. <i>Science</i>. AAAS. <a href=\"https://doi.org/10.1126/science.adg6757\">https://doi.org/10.1126/science.adg6757</a>"},"publication_identifier":{"eissn":["1095-9203"]},"language":[{"iso":"eng"}],"article_processing_charge":"No","date_published":"2024-03-08T00:00:00Z","abstract":[{"text":"The hippocampal mossy fiber synapse, formed between axons of dentate gyrus granule cells and dendrites of CA3 pyramidal neurons, is a key synapse in the trisynaptic circuitry of the hippocampus. Because of its comparatively large size, this synapse is accessible to direct presynaptic recording, allowing a rigorous investigation of the biophysical mechanisms of synaptic transmission and plasticity. Furthermore, because of its placement in the very center of the hippocampal memory circuit, this synapse seems to be critically involved in several higher network functions, such as learning, memory, pattern separation, and pattern completion. Recent work based on new technologies in both nanoanatomy and nanophysiology, including presynaptic patch-clamp recording, paired recording, super-resolution light microscopy, and freeze-fracture and “flash-and-freeze” electron microscopy, has provided new insights into the structure, biophysics, and network function of this intriguing synapse. This brings us one step closer to answering a fundamental question in neuroscience: how basic synaptic properties shape higher network computations.","lang":"eng"}],"department":[{"_id":"PeJo"}],"date_created":"2024-03-17T23:00:57Z","intvolume":"       383","doi":"10.1126/science.adg6757","issue":"6687","article_type":"review","quality_controlled":"1","scopus_import":"1"},{"type":"journal_article","publication_status":"published","volume":46,"month":"07","file":[{"relation":"main_file","access_level":"open_access","date_updated":"2025-01-09T09:31:05Z","content_type":"application/pdf","creator":"dernst","file_id":"18801","success":1,"file_name":"2024_BioEssays_Stockwell.pdf","file_size":775825,"checksum":"dc8be74156657e8aab12a9d613233ee3","date_created":"2025-01-09T09:31:05Z"}],"ddc":["570"],"oa":1,"status":"public","acknowledgement":"The authors thank Alexander Scrutton and James M. Krieger for comments on the manuscript. The authors also acknowledge Shraddha Nayak for help with Figure 1B design. This work was supported by grants from the Medical Research Council (MC_U105174197), the BBSRC (BB/N002113/1), and the Wellcome Trust (223194/Z/21/Z) to IHG.","publisher":"Wiley","external_id":{"isi":["001214545700001"],"pmid":["38693811"]},"has_accepted_license":"1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"oa_version":"Published Version","pmid":1,"article_number":" 2400006","publication":"BioEssays","day":"01","_id":"15379","year":"2024","citation":{"ama":"Stockwell I, Watson J, Greger IH. Tuning synaptic strength by regulation of AMPA glutamate receptor localization. <i>BioEssays</i>. 2024;46(7). doi:<a href=\"https://doi.org/10.1002/bies.202400006\">10.1002/bies.202400006</a>","ieee":"I. Stockwell, J. Watson, and I. H. Greger, “Tuning synaptic strength by regulation of AMPA glutamate receptor localization,” <i>BioEssays</i>, vol. 46, no. 7. Wiley, 2024.","short":"I. Stockwell, J. Watson, I.H. Greger, BioEssays 46 (2024).","chicago":"Stockwell, Imogen, Jake Watson, and Ingo H. Greger. “Tuning Synaptic Strength by Regulation of AMPA Glutamate Receptor Localization.” <i>BioEssays</i>. Wiley, 2024. <a href=\"https://doi.org/10.1002/bies.202400006\">https://doi.org/10.1002/bies.202400006</a>.","ista":"Stockwell I, Watson J, Greger IH. 2024. Tuning synaptic strength by regulation of AMPA glutamate receptor localization. BioEssays. 46(7), 2400006.","mla":"Stockwell, Imogen, et al. “Tuning Synaptic Strength by Regulation of AMPA Glutamate Receptor Localization.” <i>BioEssays</i>, vol. 46, no. 7, 2400006, Wiley, 2024, doi:<a href=\"https://doi.org/10.1002/bies.202400006\">10.1002/bies.202400006</a>.","apa":"Stockwell, I., Watson, J., &#38; Greger, I. H. (2024). Tuning synaptic strength by regulation of AMPA glutamate receptor localization. <i>BioEssays</i>. Wiley. <a href=\"https://doi.org/10.1002/bies.202400006\">https://doi.org/10.1002/bies.202400006</a>"},"publication_identifier":{"eissn":["1521-1878"],"issn":["0265-9247"]},"language":[{"iso":"eng"}],"article_processing_charge":"Yes (in subscription journal)","date_updated":"2025-09-08T07:25:02Z","isi":1,"author":[{"last_name":"Stockwell","full_name":"Stockwell, Imogen","first_name":"Imogen"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake","orcid":"0000-0002-8698-3823","last_name":"Watson","full_name":"Watson, Jake"},{"last_name":"Greger","full_name":"Greger, Ingo H.","first_name":"Ingo H."}],"title":"Tuning synaptic strength by regulation of AMPA glutamate receptor localization","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","OA_place":"publisher","OA_type":"hybrid","date_created":"2024-05-12T22:01:02Z","intvolume":"        46","doi":"10.1002/bies.202400006","issue":"7","article_type":"review","file_date_updated":"2025-01-09T09:31:05Z","scopus_import":"1","quality_controlled":"1","date_published":"2024-07-01T00:00:00Z","abstract":[{"text":"Long-term potentiation (LTP) of excitatory synapses is a leading model to explain the concept of information storage in the brain. Multiple mechanisms contribute to LTP, but central amongst them is an increased sensitivity of the postsynaptic membrane to neurotransmitter release. This sensitivity is predominantly determined by the abundance and localization of AMPA-type glutamate receptors (AMPARs). A combination of AMPAR structural data, super-resolution imaging of excitatory synapses, and an abundance of electrophysiological studies are providing an ever-clearer picture of how AMPARs are recruited and organized at synaptic junctions. Here, we review the latest insights into this process, and discuss how both cytoplasmic and extracellular receptor elements cooperate to tune the AMPAR response at the hippocampal CA1 synapse.","lang":"eng"}],"department":[{"_id":"PeJo"}]},{"intvolume":"        24","date_created":"2024-06-09T22:01:01Z","doi":"10.1186/s12888-024-05849-2","file_date_updated":"2024-06-10T10:44:26Z","article_type":"original","quality_controlled":"1","scopus_import":"1","date_published":"2024-05-29T00:00:00Z","abstract":[{"text":"Background: Motor alterations and lowered physical activity are common in affective disorders. Previous research has indicated a link between depressive symptoms and declining muscle strength primarily focusing on the elderly but not younger individuals. Thus, we aimed to evaluate the relationship between mood and muscle strength in a sample of N = 73 young to middle-aged hospitalized patients (18–49 years, mean age 30.7 years) diagnosed with major depressive, bipolar and schizoaffective disorder, with a focus on moderating effects of psychopharmacotherapy. The study was carried out as a prospective observational study at a German psychiatric university hospital between September 2021 and March 2022.\r\nMethods: Employing a standardized strength circuit consisting of computerized strength training devices, we measured the maximal muscle strength (Fmax) using three repetitions maximum across four muscle regions (abdomen, arm, back, leg) at three time points (t1-t3) over four weeks accompanied by psychometric testing (MADRS, BPRS, YRMS) and blood lipid profiling in a clinical setting. For analysis of psychopharmacotherapy, medication was split into activating (AM) and inhibiting (IM) medication and dosages were normalized by the respective WHO defined daily dose.\r\nResults: While we observed a significant decrease of the MADRS score and increase of the relative total Fmax (rTFmax) in the first two weeks (t1-t2) but not later (both p < .001), we did not reveal a significant bivariate correlation between disease severity (MADRS) and muscle strength (rTFmax) at any of the timepoints. Individuals with longer disease history displayed reduced rTFmax (p = .048). IM was significantly associated with decreased rTFmax (p = .032). Regression models provide a more substantial effect of gender, age, and IM on muscle strength than the depressive episode itself (p < .001).\r\nConclusions: The results of the study indicate that disease severity and muscle strength are not associated in young to middle-aged inpatients with affective disorders using a strength circuit as observational measurement. Future research will be needed to differentiate the effect of medication, gender, and age on muscle strength and to develop interventions for prevention of muscle weakness, especially in younger patients with chronic affective illnesses.","lang":"eng"}],"department":[{"_id":"PeJo"}],"year":"2024","citation":{"apa":"Ramming, H., Theuerkauf, L., Hoos, O., Lichter, K., &#38; Kittel-Schneider, S. (2024). The association between maximal muscle strength, disease severity and psychopharmacotherapy among young to middle-aged inpatients with affective disorders – a prospective pilot study. <i>BMC Psychiatry</i>. Springer Nature. <a href=\"https://doi.org/10.1186/s12888-024-05849-2\">https://doi.org/10.1186/s12888-024-05849-2</a>","mla":"Ramming, Hannah, et al. “The Association between Maximal Muscle Strength, Disease Severity and Psychopharmacotherapy among Young to Middle-Aged Inpatients with Affective Disorders – a Prospective Pilot Study.” <i>BMC Psychiatry</i>, vol. 24, 401, Springer Nature, 2024, doi:<a href=\"https://doi.org/10.1186/s12888-024-05849-2\">10.1186/s12888-024-05849-2</a>.","chicago":"Ramming, Hannah, Linda Theuerkauf, Olaf Hoos, Katharina Lichter, and Sarah Kittel-Schneider. “The Association between Maximal Muscle Strength, Disease Severity and Psychopharmacotherapy among Young to Middle-Aged Inpatients with Affective Disorders – a Prospective Pilot Study.” <i>BMC Psychiatry</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1186/s12888-024-05849-2\">https://doi.org/10.1186/s12888-024-05849-2</a>.","short":"H. Ramming, L. Theuerkauf, O. Hoos, K. Lichter, S. Kittel-Schneider, BMC Psychiatry 24 (2024).","ista":"Ramming H, Theuerkauf L, Hoos O, Lichter K, Kittel-Schneider S. 2024. The association between maximal muscle strength, disease severity and psychopharmacotherapy among young to middle-aged inpatients with affective disorders – a prospective pilot study. BMC Psychiatry. 24, 401.","ieee":"H. Ramming, L. Theuerkauf, O. Hoos, K. Lichter, and S. Kittel-Schneider, “The association between maximal muscle strength, disease severity and psychopharmacotherapy among young to middle-aged inpatients with affective disorders – a prospective pilot study,” <i>BMC Psychiatry</i>, vol. 24. Springer Nature, 2024.","ama":"Ramming H, Theuerkauf L, Hoos O, Lichter K, Kittel-Schneider S. The association between maximal muscle strength, disease severity and psychopharmacotherapy among young to middle-aged inpatients with affective disorders – a prospective pilot study. <i>BMC Psychiatry</i>. 2024;24. doi:<a href=\"https://doi.org/10.1186/s12888-024-05849-2\">10.1186/s12888-024-05849-2</a>"},"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1471-244X"]},"article_processing_charge":"Yes (via OA deal)","date_updated":"2025-04-23T07:51:51Z","author":[{"first_name":"Hannah","last_name":"Ramming","full_name":"Ramming, Hannah"},{"full_name":"Theuerkauf, Linda","last_name":"Theuerkauf","first_name":"Linda"},{"first_name":"Olaf","full_name":"Hoos, Olaf","last_name":"Hoos"},{"orcid":"0000-0002-1485-0351","first_name":"Katharina","id":"39302e62-fcfc-11ec-8196-8b01447dbd3d","full_name":"Lichter, Katharina","last_name":"Lichter"},{"first_name":"Sarah","full_name":"Kittel-Schneider, Sarah","last_name":"Kittel-Schneider"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"The association between maximal muscle strength, disease severity and psychopharmacotherapy among young to middle-aged inpatients with affective disorders – a prospective pilot study","external_id":{"pmid":["38811916"]},"publisher":"Springer Nature","has_accepted_license":"1","oa_version":"Published Version","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"pmid":1,"article_number":"401","day":"29","publication":"BMC Psychiatry","_id":"17122","publication_status":"published","type":"journal_article","volume":24,"month":"05","file":[{"relation":"main_file","access_level":"open_access","date_updated":"2024-06-10T10:44:26Z","content_type":"application/pdf","creator":"dernst","file_id":"17131","success":1,"file_name":"2024_BMCPsychiatry_Ramming.pdf","checksum":"5df60d3c9388955c5b682ea34748d59d","date_created":"2024-06-10T10:44:26Z","file_size":2320147}],"ddc":["570"],"status":"public","oa":1,"acknowledgement":"This work was supported by the project ‘Fellows Ride’ of the Thomas Lurz und Dieter Schneider Stiftung and by the ‘Würzburger Bündnis gegen Depression’ (to S.K.-S).\r\nOpen Access funding enabled and organized by Projekt DEAL."},{"abstract":[{"lang":"eng","text":"The human brain has remarkable computational power. It generates sophisticated behavioral sequences, stores engrams over an individual’s lifetime, and produces higher cognitive functions up to the level of consciousness. However, so little of our neuroscience knowledge covers the human brain, and it remains unknown whether this organ is truly unique, or is a scaled version of the extensively studied rodent brain. To address this fundamental question, we determined the cellular, synaptic, and connectivity rules of the hippocampal CA3 recurrent circuit using multicellular patch clamp-recording. This circuit is the largest autoassociative network in the brain, and plays a key role in memory and higher-order computations such as pattern separation and pattern completion. We demonstrate that human hippocampal CA3 employs sparse connectivity, in stark contrast to neocortical recurrent networks. Connectivity sparsifies from rodents to humans, providing a circuit architecture that maximizes associational power. Unitary synaptic events at human CA3–CA3 synapses showed both distinct species-specific and circuit-dependent properties, with high reliability, unique amplitude precision, and long integration times. We also identify differential scaling rules between hippocampal pathways from rodents to humans, with a moderate increase in the convergence of CA3 inputs per cell, but a marked increase in human mossy fiber innervation. Anatomically guided full-scale modeling suggests that the human brain’s sparse connectivity, expanded neuronal number, and reliable synaptic signaling combine to enhance the associative memory storage capacity of CA3. Together, our results reveal unique rules of connectivity and synaptic signaling in the human hippocampus, demonstrating the absolute necessity of human brain research and beginning to unravel the remarkable performance of our autoassociative memory circuits."}],"oa_version":"Preprint","date_published":"2024-05-02T00:00:00Z","ec_funded":1,"_id":"18688","day":"02","publication":"bioRxiv","department":[{"_id":"JoDa"},{"_id":"PeJo"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"PreCl"},{"_id":"ScienComp"}],"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2024.05.02.592169"}],"doi":"10.1101/2024.05.02.592169","project":[{"name":"Synaptic computations of the hippocampal CA3 circuitry","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","call_identifier":"H2020","grant_number":"101026635"},{"_id":"26AA4EF2-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24","call_identifier":"FWF","name":"Molecular Drug Targets"},{"_id":"6285a163-2b32-11ec-9570-8e204ca2dba5","grant_number":"26137","name":"Studying Organelle Structure and Function at Nanoscale Resolution with Expansion Microscopy"}],"date_created":"2024-12-19T11:35:08Z","status":"public","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"18681"},{"status":"public","relation":"later_version","id":"18879"}]},"oa":1,"date_updated":"2026-04-14T08:34:32Z","OA_place":"repository","acknowledgement":"We thank Florian Marr for excellent technical assistance, Christina Altmutter and Julia Flor for technical support, Alois Schlögl for programming, Todor Asenov for development of the transportation box for human brain tissue, Tim Vogels for guidance on simulations, Marcus Huber for mathematical advice, and Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA, and we are particularly grateful for assistance from Christoph Sommer and the Imaging and Optics Facility, Preclinical Facility, Life Science Facility, Miba Machine Shop, and Scientific Computing. We also acknowledge the excellent support of the Medical University of Vienna Department of Neurosurgery staff, Romana Hoeftberger and the Division of Neuropathology and Neurochemistry, and Gregor Kasprian and the Division of Neuroradiology and Musculoskeletal Radiology. The project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 to J.F.W.), the Austrian Science Fund (FWF; grant PAT 4178023 to P.J.; grant DK W1232 to M.R.T. and J.G.D.) and the Austrian Academy of Sciences (DOC fellowship 26137 to M.R.T.).","title":"Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"last_name":"Watson","full_name":"Watson, Jake F.","first_name":"Jake F."},{"last_name":"Vargas-Barroso","full_name":"Vargas-Barroso, Victor","first_name":"Victor"},{"last_name":"Morse-Mora","full_name":"Morse-Mora, Rebecca J.","first_name":"Rebecca J."},{"first_name":"Andrea","last_name":"Navas-Olive","full_name":"Navas-Olive, Andrea"},{"last_name":"Tavakoli","full_name":"Tavakoli, Mojtaba","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7667-6854","first_name":"Mojtaba"},{"first_name":"Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","last_name":"Danzl"},{"full_name":"Tomschik, Matthias","last_name":"Tomschik","first_name":"Matthias"},{"full_name":"Rössler, Karl","last_name":"Rössler","first_name":"Karl"},{"orcid":"0000-0001-5001-4804","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","last_name":"Jonas"}],"type":"preprint","citation":{"apa":"Watson, J. F., Vargas-Barroso, V., Morse-Mora, R. J., Navas-Olive, A., Tavakoli, M., Danzl, J. G., … Jonas, P. M. (n.d.). Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/2024.05.02.592169\">https://doi.org/10.1101/2024.05.02.592169</a>","chicago":"Watson, Jake F., Victor Vargas-Barroso, Rebecca J. Morse-Mora, Andrea Navas-Olive, Mojtaba Tavakoli, Johann G Danzl, Matthias Tomschik, Karl Rössler, and Peter M Jonas. “Human Hippocampal CA3 Uses Specific Functional Connectivity Rules for Efficient Associative Memory.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.1101/2024.05.02.592169\">https://doi.org/10.1101/2024.05.02.592169</a>.","short":"J.F. Watson, V. Vargas-Barroso, R.J. Morse-Mora, A. Navas-Olive, M. Tavakoli, J.G. Danzl, M. Tomschik, K. Rössler, P.M. Jonas, BioRxiv (n.d.).","ista":"Watson JF, Vargas-Barroso V, Morse-Mora RJ, Navas-Olive A, Tavakoli M, Danzl JG, Tomschik M, Rössler K, Jonas PM. Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory. bioRxiv, <a href=\"https://doi.org/10.1101/2024.05.02.592169\">10.1101/2024.05.02.592169</a>.","mla":"Watson, Jake F., et al. “Human Hippocampal CA3 Uses Specific Functional Connectivity Rules for Efficient Associative Memory.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.1101/2024.05.02.592169\">10.1101/2024.05.02.592169</a>.","ama":"Watson JF, Vargas-Barroso V, Morse-Mora RJ, et al. Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2024.05.02.592169\">10.1101/2024.05.02.592169</a>","ieee":"J. F. Watson <i>et al.</i>, “Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory,” <i>bioRxiv</i>. ."},"publication_status":"draft","year":"2024","corr_author":"1","article_processing_charge":"No","month":"05","language":[{"iso":"eng"}]},{"type":"journal_article","publication_status":"published","volume":42,"corr_author":"1","file":[{"file_id":"18784","success":1,"file_name":"2024_NatureBiotech_Michalska.pdf","file_size":26065165,"checksum":"57d5fafb16f02dcb9f7dddb1bd7e2a71","date_created":"2025-01-09T07:48:01Z","relation":"main_file","access_level":"open_access","date_updated":"2025-01-09T07:48:01Z","content_type":"application/pdf","creator":"dernst"}],"month":"07","status":"public","ddc":["570"],"oa":1,"acknowledgement":"We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I. Erber for technical assistance; and M. Tomschik for support with obtaining human samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata for computational support and hardware control. We are grateful to R. Shigemoto and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University) for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly provided by S. Grant (University of Edinburgh). We acknowledge expert support by Institute of Science and Technology Austria’s scientific computing, imaging and optics, preclinical and lab support facilities and by the Miba machine shop and library. We gratefully acknowledge funding by the following sources: Austrian Science Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232 (J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award (P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27 (R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 692692 – GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).","page":"1051-1064","project":[{"name":"Optical control of synaptic function via adhesion molecules","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"I03600"},{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232","call_identifier":"FWF","name":"Molecular Drug Targets"},{"call_identifier":"FWF","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"Synaptic communication in neuronal microcircuits"},{"grant_number":"LS18-022","_id":"23889792-32DE-11EA-91FC-C7463DDC885E","name":"High content imaging to decode human immune cell interactions in health and allergic disease"},{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"715508"},{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","call_identifier":"H2020"},{"call_identifier":"H2020","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program"},{"name":"Synaptic computations of the hippocampal CA3 circuitry","call_identifier":"H2020","grant_number":"101026635","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9"}],"external_id":{"pmid":["37653226"],"isi":["001065254200001"]},"publisher":"Springer Nature","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"has_accepted_license":"1","oa_version":"Published Version","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"pmid":1,"publication":"Nature Biotechnology","day":"01","ec_funded":1,"_id":"14257","year":"2024","citation":{"apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (2024). Imaging brain tissue architecture across millimeter to nanometer scales. <i>Nature Biotechnology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41587-023-01911-8\">https://doi.org/10.1038/s41587-023-01911-8</a>","short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology 42 (2024) 1051–1064.","ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino G, Jonas PM, Danzl JG. 2024. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. 42, 1051–1064.","chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” <i>Nature Biotechnology</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41587-023-01911-8\">https://doi.org/10.1038/s41587-023-01911-8</a>.","mla":"Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” <i>Nature Biotechnology</i>, vol. 42, Springer Nature, 2024, pp. 1051–64, doi:<a href=\"https://doi.org/10.1038/s41587-023-01911-8\">10.1038/s41587-023-01911-8</a>.","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture across millimeter to nanometer scales. <i>Nature Biotechnology</i>. 2024;42:1051-1064. doi:<a href=\"https://doi.org/10.1038/s41587-023-01911-8\">10.1038/s41587-023-01911-8</a>","ieee":"J. M. Michalska <i>et al.</i>, “Imaging brain tissue architecture across millimeter to nanometer scales,” <i>Nature Biotechnology</i>, vol. 42. Springer Nature, pp. 1051–1064, 2024."},"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1546-1696"],"issn":["1087-0156"]},"article_processing_charge":"Yes (in subscription journal)","isi":1,"date_updated":"2026-04-14T08:34:35Z","related_material":{"link":[{"url":"https://github.com/danzllab/CATS","relation":"software"}],"record":[{"relation":"dissertation_contains","id":"18660","status":"deleted"},{"status":"public","id":"13126","relation":"research_data"},{"relation":"dissertation_contains","id":"18674","status":"public"}]},"title":"Imaging brain tissue architecture across millimeter to nanometer scales","author":[{"id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","first_name":"Julia M","orcid":"0000-0003-3862-1235","last_name":"Michalska","full_name":"Michalska, Julia M"},{"full_name":"Lyudchik, Julia","last_name":"Lyudchik","first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431","first_name":"Philipp","last_name":"Velicky","full_name":"Velicky, Philipp"},{"last_name":"Korinkova","full_name":"Korinkova, Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","first_name":"Hana"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake","orcid":"0000-0002-8698-3823","last_name":"Watson","full_name":"Watson, Jake"},{"last_name":"Cenameri","full_name":"Cenameri, Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M","orcid":"0000-0003-1216-9105","last_name":"Sommer","full_name":"Sommer, Christoph M"},{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","first_name":"Nicole","orcid":"0000-0002-3183-8207","last_name":"Amberg","full_name":"Amberg, Nicole"},{"id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","first_name":"Alessandro","orcid":"0000-0003-2356-9403","last_name":"Venturino","full_name":"Venturino, Alessandro"},{"first_name":"Karl","full_name":"Roessler, Karl","last_name":"Roessler"},{"first_name":"Thomas","last_name":"Czech","full_name":"Czech, Thomas"},{"last_name":"Höftberger","full_name":"Höftberger, Romana","first_name":"Romana"},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","first_name":"Sandra","last_name":"Siegert","full_name":"Siegert, Sandra"},{"orcid":"0000-0002-7673-7178","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","last_name":"Novarino"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","first_name":"Peter M","last_name":"Jonas","full_name":"Jonas, Peter M"},{"last_name":"Danzl","full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G","orcid":"0000-0001-8559-3973"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","OA_place":"publisher","intvolume":"        42","date_created":"2023-09-03T22:01:15Z","OA_type":"hybrid","doi":"10.1038/s41587-023-01911-8","file_date_updated":"2025-01-09T07:48:01Z","article_type":"original","quality_controlled":"1","scopus_import":"1","date_published":"2024-07-01T00:00:00Z","abstract":[{"lang":"eng","text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease."}],"department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"},{"_id":"Bio"},{"_id":"RySh"}]},{"type":"journal_article","publication_status":"published","month":"11","file":[{"relation":"main_file","access_level":"open_access","date_updated":"2024-12-03T08:56:53Z","content_type":"application/pdf","creator":"dernst","file_id":"18608","success":1,"file_name":"2024_PloSBio_Kim.pdf","checksum":"7de2dcb50deb65dde05c80082bb85a82","file_size":3057631,"date_created":"2024-12-03T08:56:53Z"}],"corr_author":"1","volume":22,"status":"public","ddc":["570"],"oa":1,"acknowledgement":"We thank Carolina Borges-Merjane, Jing-Jing Chen, Katharina Lichter, and Samuel Young for critically reading the manuscript; the Electron Microscopy Facility of ISTA, in particular Vanessa Zheden, for extensive support, advice, and experimental assistance; the Preclinical Facility of ISTA, in particular Victoria Wimmer and Michael Schunn, for experimental assistance; Florian Marr and Christina Altmutter for technical support; Alois Schlögl for help with analysis; and Eleftheria Kralli-Beller for manuscript editing. We also thank Cordelia Imig for providing Munc13-1cKO-Munc13-2/3(−/−) mutant mice. Part of the work has been published in O.K.’s thesis in partial fulfillment of the requirements for the degree of Doctor of Philosophy.\r\nThis project received funding from the European Research Council and European Union’s Horizon 2020 research and innovation programme (ERC 692692 to P.J.; https://cordis.europa.eu/project/id/692692/de) and from the Fond zur Förderung der Wissenschaftlichen Forschung (Z312-B27 Wittgenstein award to P.J., https://www.fwf.ac.at/en/funding/portfolio/projects/fwf-wittgenstein-award; W1205-B09 and P36232-B to P.J., https://www.fwf.ac.at/en/funding; I6166-B to R.S.; https://www.fwf.ac.at/en/funding). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"PreCl"}],"publisher":"Public Library of Science","project":[{"call_identifier":"H2020","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Z00312","name":"Synaptic communication in neuronal microcircuits"},{"grant_number":"P36232","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","name":"Mechanisms of GABA release in hippocampal circuits"},{"name":"Structural & functional basis of presynaptic plasticity","grant_number":"I06166","_id":"b1b85715-d554-11ed-a5ad-84a07fc9f18e"},{"name":"Zellkommunikation in Gesundheit und Krankheit","_id":"25C3DBB6-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"W01205"},{"_id":"3AC91DDA-15DF-11EA-824D-93A3E7B544D1","call_identifier":"FWF","name":"FWF Open Access Fund"}],"external_id":{"isi":["001358568700003"],"pmid":["39556620"]},"has_accepted_license":"1","pmid":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"oa_version":"Published Version","_id":"18603","ec_funded":1,"day":"18","publication":"PLoS Biology","article_number":"e3002879","citation":{"apa":"Kim, O., Okamoto, Y., Kaufmann, W., Brose, N., Shigemoto, R., &#38; Jonas, P. M. (2024). Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. <i>PLoS Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pbio.3002879\">https://doi.org/10.1371/journal.pbio.3002879</a>","mla":"Kim, Olena, et al. “Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber Boutons.” <i>PLoS Biology</i>, vol. 22, no. 11, e3002879, Public Library of Science, 2024, doi:<a href=\"https://doi.org/10.1371/journal.pbio.3002879\">10.1371/journal.pbio.3002879</a>.","short":"O. Kim, Y. Okamoto, W. Kaufmann, N. Brose, R. Shigemoto, P.M. Jonas, PLoS Biology 22 (2024).","chicago":"Kim, Olena, Yuji Okamoto, Walter Kaufmann, Nils Brose, Ryuichi Shigemoto, and Peter M Jonas. “Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber Boutons.” <i>PLoS Biology</i>. Public Library of Science, 2024. <a href=\"https://doi.org/10.1371/journal.pbio.3002879\">https://doi.org/10.1371/journal.pbio.3002879</a>.","ista":"Kim O, Okamoto Y, Kaufmann W, Brose N, Shigemoto R, Jonas PM. 2024. Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. PLoS Biology. 22(11), e3002879.","ieee":"O. Kim, Y. Okamoto, W. Kaufmann, N. Brose, R. Shigemoto, and P. M. Jonas, “Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons,” <i>PLoS Biology</i>, vol. 22, no. 11. Public Library of Science, 2024.","ama":"Kim O, Okamoto Y, Kaufmann W, Brose N, Shigemoto R, Jonas PM. Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. <i>PLoS Biology</i>. 2024;22(11). doi:<a href=\"https://doi.org/10.1371/journal.pbio.3002879\">10.1371/journal.pbio.3002879</a>"},"APC_amount":"6248,82 EUR","year":"2024","DOAJ_listed":"1","article_processing_charge":"Yes","publication_identifier":{"eissn":["1545-7885"],"issn":["1544-9173"]},"language":[{"iso":"eng"}],"related_material":{"record":[{"id":"18296","relation":"research_data","status":"public"}]},"date_updated":"2026-04-16T12:20:34Z","isi":1,"OA_place":"publisher","title":"Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons","author":[{"full_name":"Kim, Olena","last_name":"Kim","orcid":"0000-0003-2344-1039","first_name":"Olena","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Okamoto, Yuji","last_name":"Okamoto","first_name":"Yuji","orcid":"0000-0003-0408-6094","id":"3337E116-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Kaufmann","full_name":"Kaufmann, Walter","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9735-5315","first_name":"Walter"},{"full_name":"Brose, Nils","last_name":"Brose","first_name":"Nils"},{"full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","first_name":"Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","last_name":"Jonas"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","doi":"10.1371/journal.pbio.3002879","OA_type":"gold","date_created":"2024-12-01T23:01:54Z","intvolume":"        22","quality_controlled":"1","scopus_import":"1","issue":"11","article_type":"original","file_date_updated":"2024-12-03T08:56:53Z","abstract":[{"lang":"eng","text":"It is widely believed that information storage in neuronal circuits involves nanoscopic structural changes at synapses, resulting in the formation of synaptic engrams. However, direct evidence for this hypothesis is lacking. To test this conjecture, we combined chemical potentiation, functional analysis by paired pre-postsynaptic recordings, and structural analysis by electron microscopy (EM) and freeze-fracture replica labeling (FRL) at the rodent hippocampal mossy fiber synapse, a key synapse in the trisynaptic circuit of the hippocampus. Biophysical analysis of synaptic transmission revealed that forskolin-induced chemical potentiation increased the readily releasable vesicle pool size and vesicular release probability by 146% and 49%, respectively. Structural analysis of mossy fiber synapses by EM and FRL demonstrated an increase in the number of vesicles close to the plasma membrane and the number of clusters of the priming protein Munc13-1, indicating an increase in the number of both docked and primed vesicles. Furthermore, FRL analysis revealed a significant reduction of the distance between Munc13-1 and CaV2.1 Ca2+ channels, suggesting reconfiguration of the channel-vesicle coupling nanotopography. Our results indicate that presynaptic plasticity is associated with structural reorganization of active zones. We propose that changes in potential nanoscopic organization at synaptic vesicle release sites may be correlates of learning and memory at a plastic central synapse."}],"date_published":"2024-11-18T00:00:00Z","department":[{"_id":"PeJo"},{"_id":"EM-Fac"},{"_id":"RySh"}]},{"project":[{"grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"}],"publisher":"Institute of Science and Technology Austria","has_accepted_license":"1","oa_version":"Submitted Version","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"day":"11","ec_funded":1,"_id":"18296","keyword":["Hippocampal mossy fiber synapses","short-term potentiation","long-term potentiation","presynaptic plasticity","electron microscopy","freeze-fracture replica labeling","paired recordings","forskolin","cyclic adenosine monophosphate (cAMP)","protein kinase A (PKA)","neuromodulation","synaptic vesicle pools","presynaptic Ca2+ channels","Munc13","docking","priming","active zone"],"type":"research_data","corr_author":"1","month":"10","file":[{"creator":"okim","date_updated":"2024-10-11T10:04:19Z","content_type":"application/zip","access_level":"open_access","relation":"main_file","file_name":"Kim_et_al_2024_PlosBio_Source_data.zip","checksum":"0a977e7df54c418251b10dfd3f8a015c","date_created":"2024-10-11T10:04:19Z","file_size":164382,"success":1,"file_id":"18297"},{"relation":"main_file","access_level":"open_access","date_updated":"2024-10-11T10:04:23Z","content_type":"text/plain","creator":"okim","file_id":"18298","success":1,"file_name":"info.txt","checksum":"5b9343d6b2035ac3185e390fad4d3830","file_size":654,"date_created":"2024-10-11T10:04:23Z"}],"status":"public","oa":1,"ddc":["570"],"date_created":"2024-10-11T10:12:17Z","doi":"10.15479/AT:ISTA:18296","file_date_updated":"2024-10-11T10:04:23Z","date_published":"2024-10-11T00:00:00Z","abstract":[{"lang":"eng","text":"It is widely believed that information storage in neuronal circuits involves nanoscopic structural changes at synapses, resulting in the formation of synaptic engrams. However, direct evidence for this hypothesis is lacking. To test this conjecture, we combined chemical potentiation, functional analysis by paired pre-postsynaptic recordings, and structural analysis by electron microscopy (EM) and freeze-fracture replica labeling (FRL) at the murine hippocampal mossy fiber synapse, a key synapse in the trisynaptic circuit of the hippocampus. Biophysical analysis of synaptic transmission revealed that forskolin-induced chemical potentiation increased the readily releasable vesicle pool size and vesicular release probability by 146% and 49%, respectively. Structural analysis of mossy fiber synapses by EM and FRL demonstrated an increase in the number of vesicles close to the plasma membrane and the number of clusters of the priming protein Munc13-1, indicating an increase in the number of both docked and primed vesicles. Furthermore, FRL analysis revealed a significant reduction of the distance between Munc13-1 and CaV2.1 Ca2+ channels, suggesting reconfiguration of the channel-vesicle coupling nanotopography. Our results indicate that presynaptic plasticity is associated with structural reorganization of active zones. We propose that changes in potential nanoscopic organization at synaptic vesicle release sites may be correlates of learning and memory at a plastic central synapse."}],"department":[{"_id":"PeJo"},{"_id":"RySh"},{"_id":"EM-Fac"}],"year":"2024","citation":{"ieee":"O. Kim, “Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons.” Institute of Science and Technology Austria, 2024.","ama":"Kim O. Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. 2024. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:18296\">10.15479/AT:ISTA:18296</a>","apa":"Kim, O. (2024). Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:18296\">https://doi.org/10.15479/AT:ISTA:18296</a>","mla":"Kim, Olena. <i>Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber Boutons</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:18296\">10.15479/AT:ISTA:18296</a>.","short":"O. Kim, (2024).","chicago":"Kim, Olena. “Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber Boutons.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/AT:ISTA:18296\">https://doi.org/10.15479/AT:ISTA:18296</a>.","ista":"Kim O. 2024. Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:18296\">10.15479/AT:ISTA:18296</a>."},"article_processing_charge":"No","date_updated":"2026-04-16T12:20:33Z","contributor":[{"last_name":"Kim","contributor_type":"researcher","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","first_name":"Olena"},{"last_name":"Okamoto","contributor_type":"researcher","id":"3337E116-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0408-6094","first_name":"Yuji"},{"id":"3F99E422-F248-11E8-B48F-1D18A9856A87","first_name":"Walter","orcid":"0000-0001-9735-5315","last_name":"Kaufmann","contributor_type":"researcher"},{"last_name":"Brose","contributor_type":"researcher","first_name":"Nils "},{"contributor_type":"researcher","last_name":"Shigemoto","orcid":"0000-0001-8761-9444","first_name":"Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87"},{"contributor_type":"supervisor","last_name":"Jonas","orcid":"0000-0001-5001-4804","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"related_material":{"record":[{"status":"public","id":"18603","relation":"used_in_publication"}]},"user_id":"68b8ca59-c5b3-11ee-8790-cd641c68093d","title":"Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons","author":[{"id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","first_name":"Olena","orcid":"0000-0003-2344-1039","last_name":"Kim","full_name":"Kim, Olena"}]},{"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.","oa":1,"ddc":["570"],"status":"public","volume":121,"month":"02","file":[{"creator":"dernst","content_type":"application/pdf","date_updated":"2024-03-12T13:42:42Z","access_level":"open_access","relation":"main_file","file_size":13648221,"checksum":"b25b2a057c266ff317a48b0d54d6fc8a","date_created":"2024-03-12T13:42:42Z","file_name":"2024_PNAS_Koppensteiner.pdf","success":1,"file_id":"15110"}],"corr_author":"1","type":"journal_article","publication_status":"published","article_number":"e2301449121","day":"20","publication":"Proceedings of the National Academy of Sciences of the United States of America","ec_funded":1,"_id":"15084","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"oa_version":"Published Version","pmid":1,"has_accepted_license":"1","publisher":"National Academy of Sciences","external_id":{"isi":["001208567300006"],"pmid":["38346189"]},"project":[{"call_identifier":"H2020","grant_number":"694539","_id":"25CA28EA-B435-11E9-9278-68D0E5697425","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour"},{"name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"665385"}],"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"title":"GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles","author":[{"id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3509-1948","first_name":"Peter","last_name":"Koppensteiner","full_name":"Koppensteiner, Peter"},{"id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0863-4481","first_name":"Pradeep","last_name":"Bhandari","full_name":"Bhandari, Pradeep"},{"last_name":"Önal","full_name":"Önal, Hüseyin C","id":"4659D740-F248-11E8-B48F-1D18A9856A87","first_name":"Hüseyin C","orcid":"0000-0002-2771-2011"},{"full_name":"Borges Merjane, Carolina","last_name":"Borges Merjane","first_name":"Carolina","orcid":"0000-0003-0005-401X","id":"4305C450-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Le Monnier","full_name":"Le Monnier, Elodie","id":"3B59276A-F248-11E8-B48F-1D18A9856A87","first_name":"Elodie"},{"full_name":"Roy, Utsa","last_name":"Roy","first_name":"Utsa","id":"4d26cf11-5355-11ee-ae5a-eb05e255b9b2"},{"first_name":"Yukihiro","last_name":"Nakamura","full_name":"Nakamura, Yukihiro"},{"first_name":"Tetsushi","full_name":"Sadakata, Tetsushi","last_name":"Sadakata"},{"first_name":"Makoto","full_name":"Sanbo, Makoto","last_name":"Sanbo"},{"first_name":"Masumi","full_name":"Hirabayashi, Masumi","last_name":"Hirabayashi"},{"last_name":"Rhee","full_name":"Rhee, JeongSeop","first_name":"JeongSeop"},{"last_name":"Brose","full_name":"Brose, Nils","first_name":"Nils"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas","full_name":"Jonas, Peter M"},{"full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","orcid":"0000-0001-8761-9444","first_name":"Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","OA_place":"publisher","date_updated":"2026-04-21T22:30:22Z","isi":1,"related_material":{"link":[{"url":"https://ista.ac.at/en/news/neuronal-insights-flash-and-freeze-fracture/","relation":"press_release","description":"News on ISTA Website"}],"record":[{"relation":"research_data","id":"13173","status":"public"},{"relation":"dissertation_contains","id":"19271","status":"public"}]},"publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"language":[{"iso":"eng"}],"article_processing_charge":"Yes (in subscription journal)","year":"2024","APC_amount":"5887,8 EUR","citation":{"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.","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>","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>.","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).","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>."},"department":[{"_id":"RySh"},{"_id":"PeJo"}],"date_published":"2024-02-20T00:00:00Z","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."}],"article_type":"original","issue":"8","file_date_updated":"2024-03-12T13:42:42Z","scopus_import":"1","quality_controlled":"1","date_created":"2024-03-05T09:23:55Z","OA_type":"hybrid","intvolume":"       121","doi":"10.1073/pnas.2301449121"},{"page":"755-771.e9","acknowledgement":"We thank Drs. David DiGregorio and Erwin Neher for critically reading an earlier version of the manuscript, Ralf Schneggenburger for helpful discussions, Benjamin Suter and Katharina Lichter for support with image analysis, Chris Wojtan for advice on numerical solution of partial differential equations, Maria Reva for help with Ripley analysis, Alois Schlögl for programming, and Akari Hagiwara and Toshihisa Ohtsuka for anti-ELKS antibody. We are grateful to Florian Marr, Christina Altmutter, and Vanessa Zheden for excellent technical assistance and to Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA (Electron Microscopy Facility, Preclinical Facility, and Machine Shop). The project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 692692), the Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award; P 36232-B), all to P.J., and a DOC fellowship of the Austrian Academy of Sciences to J.-J.C.","oa":1,"ddc":["570"],"status":"public","corr_author":"1","month":"03","file":[{"file_id":"19614","success":1,"checksum":"30098b4f0209556ddfb3540a23d07ca5","file_size":8192355,"date_created":"2025-04-23T14:02:08Z","file_name":"2024_Neuron_Chen.pdf","relation":"main_file","access_level":"open_access","content_type":"application/pdf","date_updated":"2025-04-23T14:02:08Z","creator":"dernst"}],"volume":112,"publication_status":"published","type":"journal_article","_id":"14843","ec_funded":1,"publication":"Neuron","day":"06","pmid":1,"oa_version":"Published Version","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"has_accepted_license":"1","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"PreCl"},{"_id":"M-Shop"}],"project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"name":"Synaptic communication in neuronal microcircuits","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Z00312"},{"name":"Mechanisms of GABA release in hippocampal circuits","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","grant_number":"P36232"},{"name":"Development of nanodomain coupling between Ca2+ channels and release sensors at a central inhibitory synapse","_id":"26B66A3E-B435-11E9-9278-68D0E5697425","grant_number":"25383"}],"external_id":{"pmid":["38215739"],"isi":["001202925700001"]},"publisher":"Elsevier","OA_place":"publisher","author":[{"full_name":"Chen, JingJing","last_name":"Chen","first_name":"JingJing","id":"2C4E65C8-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Kaufmann, Walter","last_name":"Kaufmann","first_name":"Walter","orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Chong","id":"3DFD581A-F248-11E8-B48F-1D18A9856A87","full_name":"Chen, Chong","last_name":"Chen"},{"id":"32A73F6C-F248-11E8-B48F-1D18A9856A87","first_name":"Itaru","last_name":"Arai","full_name":"Arai, Itaru"},{"last_name":"Kim","full_name":"Kim, Olena","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","first_name":"Olena","orcid":"0000-0003-2344-1039"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","first_name":"Ryuichi","last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","first_name":"Peter M","last_name":"Jonas","full_name":"Jonas, Peter M"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"15101"}],"link":[{"description":"News on ISTA Website","url":"https://ista.ac.at/en/news/synapses-brought-to-the-point/","relation":"press_release"}]},"isi":1,"date_updated":"2026-04-21T22:30:25Z","article_processing_charge":"Yes (via OA deal)","language":[{"iso":"eng"}],"publication_identifier":{"issn":["0896-6273"],"eissn":["1097-4199"]},"citation":{"mla":"Chen, JingJing, et al. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” <i>Neuron</i>, vol. 112, no. 5, Elsevier, 2024, p. 755–771.e9, doi:<a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">10.1016/j.neuron.2023.12.002</a>.","short":"J. Chen, W. Kaufmann, C. Chen,  itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas, Neuron 112 (2024) 755–771.e9.","chicago":"Chen, JingJing, Walter Kaufmann, Chong Chen, itaru Arai, Olena Kim, Ryuichi Shigemoto, and Peter M Jonas. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” <i>Neuron</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">https://doi.org/10.1016/j.neuron.2023.12.002</a>.","ista":"Chen J, Kaufmann W, Chen C, Arai  itaru, Kim O, Shigemoto R, Jonas PM. 2024. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron. 112(5), 755–771.e9.","apa":"Chen, J., Kaufmann, W., Chen, C., Arai,  itaru, Kim, O., Shigemoto, R., &#38; Jonas, P. M. (2024). Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">https://doi.org/10.1016/j.neuron.2023.12.002</a>","ieee":"J. Chen <i>et al.</i>, “Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse,” <i>Neuron</i>, vol. 112, no. 5. Elsevier, p. 755–771.e9, 2024.","ama":"Chen J, Kaufmann W, Chen C, et al. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. <i>Neuron</i>. 2024;112(5):755-771.e9. doi:<a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">10.1016/j.neuron.2023.12.002</a>"},"year":"2024","department":[{"_id":"PeJo"},{"_id":"EM-Fac"},{"_id":"RySh"}],"abstract":[{"text":"The coupling between Ca2+ channels and release sensors is a key factor defining the signaling properties of a synapse. However, the coupling nanotopography at many synapses remains unknown, and it is unclear how it changes during development. To address these questions, we examined coupling at the cerebellar inhibitory basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission by paired recording and intracellular pipette perfusion revealed that the effects of exogenous Ca2+ chelators decreased during development, despite constant reliance of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked vesicles were only clustered at later developmental stages. Modeling suggested a developmental transformation from a more random to a more clustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission.","lang":"eng"}],"date_published":"2024-03-06T00:00:00Z","quality_controlled":"1","scopus_import":"1","file_date_updated":"2025-04-23T14:02:08Z","article_type":"original","issue":"5","doi":"10.1016/j.neuron.2023.12.002","PlanS_conform":"1","intvolume":"       112","OA_type":"hybrid","date_created":"2024-01-21T23:00:56Z"},{"corr_author":"1","file":[{"file_name":"Thesis_Jingjing CHEN.docx","date_created":"2024-03-11T14:10:58Z","file_size":11271363,"checksum":"db4947474ffa271e66c254b6fe876a55","file_id":"15104","creator":"jchen","date_updated":"2024-04-02T22:30:03Z","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","access_level":"closed","relation":"source_file","embargo_to":"open_access"},{"file_id":"15105","file_size":16627311,"checksum":"a5eeae8b5702cd540f5d03469bc33dde","date_created":"2024-03-11T14:11:06Z","file_name":"Thesis_Jingjing CHEN_merged.pdf","access_level":"open_access","relation":"main_file","creator":"jchen","content_type":"application/pdf","embargo":"2024-04-01","date_updated":"2024-04-02T22:30:03Z"}],"month":"03","publication_status":"published","type":"dissertation","page":"84","oa":1,"ddc":["570"],"status":"public","has_accepted_license":"1","project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","call_identifier":"H2020","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"grant_number":"Z00312","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"Synaptic communication in neuronal microcircuits"},{"name":"Mechanisms of GABA release in hippocampal circuits","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","grant_number":"P36232"},{"_id":"26B66A3E-B435-11E9-9278-68D0E5697425","grant_number":"25383","name":"Development of nanodomain coupling between Ca2+ channels and release sensors at a central inhibitory synapse"}],"publisher":"Institute of Science and Technology Austria","acknowledged_ssus":[{"_id":"EM-Fac"}],"day":"11","_id":"15101","ec_funded":1,"oa_version":"Published Version","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2663-337X"]},"article_processing_charge":"No","year":"2024","supervisor":[{"full_name":"Jonas, Peter M","last_name":"Jonas","first_name":"Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"citation":{"ama":"Chen J. Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:15101\">10.15479/at:ista:15101</a>","ieee":"J. Chen, “Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse,” Institute of Science and Technology Austria, 2024.","apa":"Chen, J. (2024). <i>Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:15101\">https://doi.org/10.15479/at:ista:15101</a>","chicago":"Chen, JingJing. “Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:15101\">https://doi.org/10.15479/at:ista:15101</a>.","short":"J. Chen, Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse, Institute of Science and Technology Austria, 2024.","ista":"Chen J. 2024. Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse. Institute of Science and Technology Austria.","mla":"Chen, JingJing. <i>Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:15101\">10.15479/at:ista:15101</a>."},"author":[{"last_name":"Chen","full_name":"Chen, JingJing","id":"2C4E65C8-F248-11E8-B48F-1D18A9856A87","first_name":"JingJing"}],"title":"Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","OA_place":"publisher","date_updated":"2026-04-07T13:24:22Z","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"14843"}]},"degree_awarded":"PhD","file_date_updated":"2024-04-02T22:30:03Z","date_created":"2024-03-11T10:09:54Z","doi":"10.15479/at:ista:15101","alternative_title":["ISTA Thesis"],"department":[{"_id":"GradSch"},{"_id":"PeJo"}],"date_published":"2024-03-11T00:00:00Z","abstract":[{"text":"The coupling between presynaptic Ca2+ channels and release sensors is a key factor that\r\ndetermines speed and efficacy of synapse transmission. At some excitatory synapses,\r\nchannel–sensor coupling becomes tighter during development, and tightening is often\r\nassociated with a switch in the reliance on different Ca2+ channel subtypes. However, the\r\ncoupling topography at many synapses remains unknown, and it is unclear how it changes\r\nduring development. To address this question, we analyzed the coupling configuration at the\r\ncerebellar basket cell (BC) to Purkinje cell (PC) synapse at different developmental stages,\r\ncombining biophysical analysis, structural analysis, and modeling.\r\nQuantal analysis of BC–PC indicated that release probability decreased, while the\r\nnumber of functional sites increased during development. Although transmitter release\r\npersistently relied on P/Q-type Ca2+ channels in the time period postnatal day 7–23, effects\r\nof the Ca2+ chelator EGTA and BAPTA applied by intracellular pipette perfusion decreased\r\nduring development, indicative of tightening of source-sensor coupling. Furthermore,\r\npresynaptic action potentials became shorter during development, suggesting reduced\r\nefficacy of Ca2+ channel activation.\r\nStructural analysis by freeze-fracture replica labeling (FRL) and transmission electron\r\nmicroscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters\r\nthroughout development, whereas docked vesicles were only clustered at later\r\ndevelopmental stages. The number of functional release sites correlated better with the AZ\r\nnumber early in development, but match better with the Ca2+ channel cluster number at later\r\nstages.\r\nModeling suggested a developmental transformation from a more random to a more\r\nclustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches\r\na point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic\r\ntransmission.","lang":"eng"}]},{"department":[{"_id":"PeJo"}],"abstract":[{"text":"Introduction: The olfactory system in most mammals is divided into several subsystems based on the anatomical locations of the neuroreceptor cells involved and the receptor families that are expressed. In addition to the main olfactory system and the vomeronasal system, a range of olfactory subsystems converge onto the transition zone located between the main olfactory bulb (MOB) and the accessory olfactory bulb (AOB), which has been termed the olfactory limbus (OL). The OL contains specialized glomeruli that receive noncanonical sensory afferences and which interact with the MOB and AOB. Little is known regarding the olfactory subsystems of mammals other than laboratory rodents.\r\nMethods: We have focused on characterizing the OL in the red fox by performing general and specific histological stainings on serial sections, using both single and double immunohistochemical and lectin-histochemical labeling techniques.\r\nResults: As a result, we have been able to determine that the OL of the red fox (Vulpes vulpes) displays an uncommonly high degree of development and complexity.\r\nDiscussion: This makes this species a novel mammalian model, the study of which could improve our understanding of the noncanonical pathways involved in the processing of chemosensory cues.","lang":"eng"}],"date_published":"2023-01-10T00:00:00Z","scopus_import":"1","quality_controlled":"1","file_date_updated":"2023-02-06T07:56:14Z","article_type":"original","doi":"10.3389/fnana.2022.1097467","intvolume":"        16","date_created":"2023-02-05T23:01:00Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway","author":[{"first_name":"Irene","full_name":"Ortiz-Leal, Irene","last_name":"Ortiz-Leal"},{"last_name":"Torres","full_name":"Torres, Mateo V.","first_name":"Mateo V."},{"id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87","first_name":"Victor M","last_name":"Vargas Barroso","full_name":"Vargas Barroso, Victor M"},{"last_name":"Fidalgo","full_name":"Fidalgo, Luis Eusebio","first_name":"Luis Eusebio"},{"last_name":"López-Beceiro","full_name":"López-Beceiro, Ana María","first_name":"Ana María"},{"first_name":"Jorge A.","last_name":"Larriva-Sahd","full_name":"Larriva-Sahd, Jorge A."},{"full_name":"Sánchez-Quinteiro, Pablo","last_name":"Sánchez-Quinteiro","first_name":"Pablo"}],"isi":1,"date_updated":"2023-08-16T11:37:52Z","article_processing_charge":"No","language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1662-5129"]},"citation":{"ieee":"I. Ortiz-Leal <i>et al.</i>, “The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway,” <i>Frontiers in Neuroanatomy</i>, vol. 16. Frontiers, 2023.","ama":"Ortiz-Leal I, Torres MV, Vargas Barroso VM, et al. The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway. <i>Frontiers in Neuroanatomy</i>. 2023;16. doi:<a href=\"https://doi.org/10.3389/fnana.2022.1097467\">10.3389/fnana.2022.1097467</a>","apa":"Ortiz-Leal, I., Torres, M. V., Vargas Barroso, V. M., Fidalgo, L. E., López-Beceiro, A. M., Larriva-Sahd, J. A., &#38; Sánchez-Quinteiro, P. (2023). The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway. <i>Frontiers in Neuroanatomy</i>. Frontiers. <a href=\"https://doi.org/10.3389/fnana.2022.1097467\">https://doi.org/10.3389/fnana.2022.1097467</a>","mla":"Ortiz-Leal, Irene, et al. “The Olfactory Limbus of the Red Fox (Vulpes Vulpes). New Insights Regarding a Noncanonical Olfactory Bulb Pathway.” <i>Frontiers in Neuroanatomy</i>, vol. 16, 1097467, Frontiers, 2023, doi:<a href=\"https://doi.org/10.3389/fnana.2022.1097467\">10.3389/fnana.2022.1097467</a>.","short":"I. Ortiz-Leal, M.V. Torres, V.M. Vargas Barroso, L.E. Fidalgo, A.M. López-Beceiro, J.A. Larriva-Sahd, P. Sánchez-Quinteiro, Frontiers in Neuroanatomy 16 (2023).","chicago":"Ortiz-Leal, Irene, Mateo V. Torres, Victor M Vargas Barroso, Luis Eusebio Fidalgo, Ana María López-Beceiro, Jorge A. Larriva-Sahd, and Pablo Sánchez-Quinteiro. “The Olfactory Limbus of the Red Fox (Vulpes Vulpes). New Insights Regarding a Noncanonical Olfactory Bulb Pathway.” <i>Frontiers in Neuroanatomy</i>. Frontiers, 2023. <a href=\"https://doi.org/10.3389/fnana.2022.1097467\">https://doi.org/10.3389/fnana.2022.1097467</a>.","ista":"Ortiz-Leal I, Torres MV, Vargas Barroso VM, Fidalgo LE, López-Beceiro AM, Larriva-Sahd JA, Sánchez-Quinteiro P. 2023. The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway. Frontiers in Neuroanatomy. 16, 1097467."},"year":"2023","_id":"12515","article_number":"1097467","publication":"Frontiers in Neuroanatomy","day":"10","pmid":1,"oa_version":"Published Version","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"has_accepted_license":"1","external_id":{"isi":["000919786900001"],"pmid":["36704406"]},"publisher":"Frontiers","acknowledgement":"This work was partially supported by a grant from “Consello Social Universidade de Santiago de Compostela” 2022-PU004.We would like to show special gratitude to Prof. Ludwig Wagner (Medical University, Vienna) for kindly providing us with the secretagogin antibody. We thank the Wildlife Recovery Centres of Galicia, Dirección Xeral de Patrimonio Natural (Xunta de Galicia, Spain), and Federación Galega de Caza for providing the red foxes used in this study.","oa":1,"ddc":["570"],"status":"public","month":"01","file":[{"file_id":"12518","success":1,"file_name":"2022_FrontiersNeuroanatomy_OrtizLeal.pdf","file_size":21943473,"date_created":"2023-02-06T07:56:14Z","checksum":"49cd40f3bda6f267079427042e7d15e3","relation":"main_file","access_level":"open_access","date_updated":"2023-02-06T07:56:14Z","content_type":"application/pdf","creator":"dernst"}],"volume":16,"type":"journal_article","publication_status":"published"},{"status":"public","ddc":["570"],"oa":1,"acknowledgement":"This work has been supported by funding of the German Research Foundation (Deutsche Forschungsgemeinschaft [DFG], CRC 166, Project B06 to M.H. and A.-L.S., FOR 3004 SYNABS P1 to M.H.) and by the Interdisciplinary Clinical Research Center (IZKF) Würzburg (Z-3/69 to M.M.P., N-229 to M.H. and A.-L.S.). A.M. is funded by the University of Leipzig Clinician Scientist Program.","type":"journal_article","publication_status":"published","volume":24,"month":"01","file":[{"access_level":"open_access","relation":"main_file","creator":"dernst","content_type":"application/pdf","date_updated":"2023-02-20T07:09:27Z","success":1,"file_id":"12569","date_created":"2023-02-20T07:09:27Z","checksum":"69a35dcd3e0249f902ab881b06ee2e58","file_size":2823025,"file_name":"2023_IJMS_Mrestani.pdf"}],"oa_version":"Published Version","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"pmid":1,"publication":"International Journal of Molecular Sciences","day":"21","article_number":"2128","_id":"12567","external_id":{"isi":["000930324700001"],"pmid":["36768451"]},"publisher":"MDPI","has_accepted_license":"1","isi":1,"date_updated":"2025-04-23T08:48:27Z","author":[{"first_name":"Achmed","full_name":"Mrestani, Achmed","last_name":"Mrestani"},{"last_name":"Lichter","full_name":"Lichter, Katharina","id":"39302e62-fcfc-11ec-8196-8b01447dbd3d","orcid":"0000-0002-1485-0351","first_name":"Katharina"},{"first_name":"Anna Leena","full_name":"Sirén, Anna Leena","last_name":"Sirén"},{"last_name":"Heckmann","full_name":"Heckmann, Manfred","first_name":"Manfred"},{"last_name":"Paul","full_name":"Paul, Mila M.","first_name":"Mila M."},{"last_name":"Pauli","full_name":"Pauli, Martin","first_name":"Martin"}],"title":"Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2023","citation":{"ama":"Mrestani A, Lichter K, Sirén AL, Heckmann M, Paul MM, Pauli M. Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation. <i>International Journal of Molecular Sciences</i>. 2023;24(3). doi:<a href=\"https://doi.org/10.3390/ijms24032128\">10.3390/ijms24032128</a>","ieee":"A. Mrestani, K. Lichter, A. L. Sirén, M. Heckmann, M. M. Paul, and M. Pauli, “Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation,” <i>International Journal of Molecular Sciences</i>, vol. 24, no. 3. MDPI, 2023.","short":"A. Mrestani, K. Lichter, A.L. Sirén, M. Heckmann, M.M. Paul, M. Pauli, International Journal of Molecular Sciences 24 (2023).","chicago":"Mrestani, Achmed, Katharina Lichter, Anna Leena Sirén, Manfred Heckmann, Mila M. Paul, and Martin Pauli. “Single-Molecule Localization Microscopy of Presynaptic Active Zones in Drosophila Melanogaster after Rapid Cryofixation.” <i>International Journal of Molecular Sciences</i>. MDPI, 2023. <a href=\"https://doi.org/10.3390/ijms24032128\">https://doi.org/10.3390/ijms24032128</a>.","ista":"Mrestani A, Lichter K, Sirén AL, Heckmann M, Paul MM, Pauli M. 2023. Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation. International Journal of Molecular Sciences. 24(3), 2128.","mla":"Mrestani, Achmed, et al. “Single-Molecule Localization Microscopy of Presynaptic Active Zones in Drosophila Melanogaster after Rapid Cryofixation.” <i>International Journal of Molecular Sciences</i>, vol. 24, no. 3, 2128, MDPI, 2023, doi:<a href=\"https://doi.org/10.3390/ijms24032128\">10.3390/ijms24032128</a>.","apa":"Mrestani, A., Lichter, K., Sirén, A. L., Heckmann, M., Paul, M. M., &#38; Pauli, M. (2023). Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation. <i>International Journal of Molecular Sciences</i>. MDPI. <a href=\"https://doi.org/10.3390/ijms24032128\">https://doi.org/10.3390/ijms24032128</a>"},"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1422-0067"]},"article_processing_charge":"No","date_published":"2023-01-21T00:00:00Z","abstract":[{"text":"Single-molecule localization microscopy (SMLM) greatly advances structural studies of diverse biological tissues. For example, presynaptic active zone (AZ) nanotopology is resolved in increasing detail. Immunofluorescence imaging of AZ proteins usually relies on epitope preservation using aldehyde-based immunocompetent fixation. Cryofixation techniques, such as high-pressure freezing (HPF) and freeze substitution (FS), are widely used for ultrastructural studies of presynaptic architecture in electron microscopy (EM). HPF/FS demonstrated nearer-to-native preservation of AZ ultrastructure, e.g., by facilitating single filamentous structures. Here, we present a protocol combining the advantages of HPF/FS and direct stochastic optical reconstruction microscopy (dSTORM) to quantify nanotopology of the AZ scaffold protein Bruchpilot (Brp) at neuromuscular junctions (NMJs) of Drosophila melanogaster. Using this standardized model, we tested for preservation of Brp clusters in different FS protocols compared to classical aldehyde fixation. In HPF/FS samples, presynaptic boutons were structurally well preserved with ~22% smaller Brp clusters that allowed quantification of subcluster topology. In summary, we established a standardized near-to-native preparation and immunohistochemistry protocol for SMLM analyses of AZ protein clusters in a defined model synapse. Our protocol could be adapted to study protein arrangements at single-molecule resolution in other intact tissue preparations.","lang":"eng"}],"department":[{"_id":"PeJo"}],"intvolume":"        24","date_created":"2023-02-19T23:00:56Z","doi":"10.3390/ijms24032128","file_date_updated":"2023-02-20T07:09:27Z","issue":"3","article_type":"original","scopus_import":"1","quality_controlled":"1"},{"oa_version":"Submitted Version","pmid":1,"publication":"DNA Manipulation and Analysis","day":"01","_id":"12720","publisher":"Springer Nature","external_id":{"pmid":["36853454"]},"place":"New York, NY, United States","main_file_link":[{"open_access":"1","url":"https://zaguan.unizar.es/record/125930/files/texto_completo.pdf"}],"status":"public","oa":1,"page":"33-44","publication_status":"published","type":"book_chapter","volume":2633,"month":"03","date_published":"2023-03-01T00:00:00Z","abstract":[{"lang":"eng","text":"Here we describe the in vivo DNA assembly approach, where molecular cloning procedures are performed using an E. coli recA-independent recombination pathway, which assembles linear fragments of DNA with short homologous termini. This pathway is present in all standard laboratory E. coli strains and, by bypassing the need for in vitro DNA assembly, allows simplified molecular cloning to be performed without the plasmid instability issues associated with specialized recombination-cloning bacterial strains. The methodology requires specific primer design and can perform all standard plasmid modifications (insertions, deletions, mutagenesis, and sub-cloning) in a rapid, simple, and cost-efficient manner, as it does not require commercial kits or specialized bacterial strains. Additionally, this approach can be used to perform complex procedures such as multiple modifications to a plasmid, as up to 6 linear fragments can be assembled in vivo by this recombination pathway. Procedures generally require less than 3 h, involving PCR amplification, DpnI digestion of template DNA, and transformation, upon which circular plasmids are assembled. In this chapter we describe the requirements, procedure, and potential pitfalls when using this technique, as well as protocol variations to overcome the most common issues."}],"department":[{"_id":"PeJo"}],"alternative_title":["Methods in Molecular Biology"],"OA_type":"green","date_created":"2023-03-12T23:01:02Z","intvolume":"      2633","doi":"10.1007/978-1-0716-3004-4_3","quality_controlled":"1","scopus_import":"1","date_updated":"2025-06-25T05:56:45Z","editor":[{"first_name":"Garry","full_name":"Scarlett, Garry","last_name":"Scarlett"}],"author":[{"first_name":"Sandra","full_name":"Arroyo-Urea, Sandra","last_name":"Arroyo-Urea"},{"orcid":"0000-0002-8698-3823","first_name":"Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","full_name":"Watson, Jake","last_name":"Watson"},{"first_name":"Javier","last_name":"García-Nafría","full_name":"García-Nafría, Javier"}],"title":"Molecular Cloning Using In Vivo DNA Assembly","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","OA_place":"repository","year":"2023","series_title":"MIMB","citation":{"ieee":"S. Arroyo-Urea, J. Watson, and J. García-Nafría, “Molecular Cloning Using In Vivo DNA Assembly,” in <i>DNA Manipulation and Analysis</i>, vol. 2633, G. Scarlett, Ed. New York, NY, United States: Springer Nature, 2023, pp. 33–44.","ama":"Arroyo-Urea S, Watson J, García-Nafría J. Molecular Cloning Using In Vivo DNA Assembly. In: Scarlett G, ed. <i>DNA Manipulation and Analysis</i>. Vol 2633. MIMB. New York, NY, United States: Springer Nature; 2023:33-44. doi:<a href=\"https://doi.org/10.1007/978-1-0716-3004-4_3\">10.1007/978-1-0716-3004-4_3</a>","mla":"Arroyo-Urea, Sandra, et al. “Molecular Cloning Using In Vivo DNA Assembly.” <i>DNA Manipulation and Analysis</i>, edited by Garry Scarlett, vol. 2633, Springer Nature, 2023, pp. 33–44, doi:<a href=\"https://doi.org/10.1007/978-1-0716-3004-4_3\">10.1007/978-1-0716-3004-4_3</a>.","short":"S. Arroyo-Urea, J. Watson, J. García-Nafría, in:, G. Scarlett (Ed.), DNA Manipulation and Analysis, Springer Nature, New York, NY, United States, 2023, pp. 33–44.","chicago":"Arroyo-Urea, Sandra, Jake Watson, and Javier García-Nafría. “Molecular Cloning Using In Vivo DNA Assembly.” In <i>DNA Manipulation and Analysis</i>, edited by Garry Scarlett, 2633:33–44. MIMB. New York, NY, United States: Springer Nature, 2023. <a href=\"https://doi.org/10.1007/978-1-0716-3004-4_3\">https://doi.org/10.1007/978-1-0716-3004-4_3</a>.","ista":"Arroyo-Urea S, Watson J, García-Nafría J. 2023.Molecular Cloning Using In Vivo DNA Assembly. In: DNA Manipulation and Analysis. Methods in Molecular Biology, vol. 2633, 33–44.","apa":"Arroyo-Urea, S., Watson, J., &#38; García-Nafría, J. (2023). Molecular Cloning Using In Vivo DNA Assembly. In G. Scarlett (Ed.), <i>DNA Manipulation and Analysis</i> (Vol. 2633, pp. 33–44). New York, NY, United States: Springer Nature. <a href=\"https://doi.org/10.1007/978-1-0716-3004-4_3\">https://doi.org/10.1007/978-1-0716-3004-4_3</a>"},"publication_identifier":{"eisbn":["978-1-0716-3004-4"],"issn":["1064-3745"],"isbn":["978-1-0716-3003-7"],"eissn":["1940-6029"]},"language":[{"iso":"eng"}],"article_processing_charge":"No"}]