[{"article_processing_charge":"Yes","researchdata_availability":"yes","year":"2026","project":[{"grant_number":"692692","call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"_id":"e62b56fe-ab3c-11f0-94c7-d181dd352b3b","name":"Synaptic mechanisms of engram storage and retrieval in CA3 hippocampal microcircuits","grant_number":"101199096"},{"name":"ISTplus - Postdoctoral Fellowships","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411","call_identifier":"H2020"},{"name":"Synaptic computations of the hippocampal CA3 circuitry","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","grant_number":"101026635","call_identifier":"H2020"},{"grant_number":"P36232","name":"Mechanisms of GABA release in hippocampal circuits","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5"},{"name":"Synaptic networks of human brain","_id":"8d9195e9-16d5-11f0-9cad-d075be887a1e","grant_number":"PAT 4178023"},{"name":"Reglas de Conectividad funcional en el hipocampo","_id":"26366136-B435-11E9-9278-68D0E5697425"}],"corr_author":"1","oa_version":"Published Version","publication_identifier":{"eissn":["2041-1723"]},"language":[{"iso":"eng"}],"author":[{"first_name":"Victor M","id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87","full_name":"Vargas Barroso, Victor M","last_name":"Vargas Barroso"},{"last_name":"Watson","full_name":"Watson, Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823","first_name":"Jake"},{"id":"739d26c9-52e8-11ee-8d72-f14d3893b4ce","first_name":"Andrea C","orcid":"0000-0002-9280-8597","last_name":"Navas Olivé","full_name":"Navas Olivé, Andrea C"},{"orcid":"0000-0002-5621-8100","first_name":"Alois","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","full_name":"Schlögl, Alois","last_name":"Schlögl"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas","full_name":"Jonas, Peter M"}],"file_date_updated":"2026-07-01T06:46:06Z","DOAJ_listed":"1","citation":{"ama":"Vargas Barroso VM, Watson J, Navas Olivé AC, Schlögl A, Jonas PM. Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit. <i>Nature Communications</i>. 2026;17. doi:<a href=\"https://doi.org/10.1038/s41467-026-71914-x\">10.1038/s41467-026-71914-x</a>","chicago":"Vargas Barroso, Victor M, Jake Watson, Andrea C Navas Olivé, Alois Schlögl, and Peter M Jonas. “Developmental Emergence of Sparse and Structured Synaptic Connectivity in the Hippocampal CA3 Memory Circuit.” <i>Nature Communications</i>. Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s41467-026-71914-x\">https://doi.org/10.1038/s41467-026-71914-x</a>.","mla":"Vargas Barroso, Victor M., et al. “Developmental Emergence of Sparse and Structured Synaptic Connectivity in the Hippocampal CA3 Memory Circuit.” <i>Nature Communications</i>, vol. 17, 5540, Springer Nature, 2026, doi:<a href=\"https://doi.org/10.1038/s41467-026-71914-x\">10.1038/s41467-026-71914-x</a>.","short":"V.M. Vargas Barroso, J. Watson, A.C. Navas Olivé, A. Schlögl, P.M. Jonas, Nature Communications 17 (2026).","ieee":"V. M. Vargas Barroso, J. Watson, A. C. Navas Olivé, A. Schlögl, and P. M. Jonas, “Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit,” <i>Nature Communications</i>, vol. 17. Springer Nature, 2026.","ista":"Vargas Barroso VM, Watson J, Navas Olivé AC, Schlögl A, Jonas PM. 2026. Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit. Nature Communications. 17, 5540.","apa":"Vargas Barroso, V. M., Watson, J., Navas Olivé, A. C., Schlögl, A., &#38; Jonas, P. M. (2026). Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-026-71914-x\">https://doi.org/10.1038/s41467-026-71914-x</a>"},"publication_status":"published","article_number":"5540","publication":"Nature Communications","ddc":["570"],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"intvolume":"        17","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"M-Shop"},{"_id":"ScienComp"}],"title":"Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit","external_id":{"pmid":["42014695"]},"supplementarymaterial":"yes","month":"06","volume":17,"oa":1,"OA_type":"gold","OA_place":"publisher","ec_funded":1,"pmid":1,"acknowledgement":"We thank Jose Guzman, Simon Hippenmeyer, and Tim Vogels for critically reading the manuscript, Jozsef Csicsvari for useful discussions, Florian Marr for technical assistance, and Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA: the preclinical facility (PCF) provided housing and breeding of the animals, the imaging and optics facility (IOF) offered technical training and state of the art equipment, the Miba machine shop contributed to the construction and maintenance of multicellular recording setups, and the scientific computing unit helped with the large-scale simulations. The project received funding from the European Union’s Horizon 2020 research and innovation programme (ERC Advanced Grants No 692692 GIANTSYN and 101199096 CA3-SYNGRAM to P.J.; Marie Skłodowska-Curie Grant 754411 to V.V.B.; Marie Skłodowska-Curie Grant 101026635 to J.F.W.), the Fond zur Förderung der Wissenschaftlichen Forschung (P 36232-B, PAT4178023, and 10.55776/CoE16 to P.J.), and the Nomis Foundation (fellowship to A.N.-O.). V.V.B. received funding from a CONACyT fellowship (289638).","_id":"22229","related_material":{"record":[{"status":"public","id":"21442","relation":"research_data"}]},"date_updated":"2026-07-01T06:47:49Z","abstract":[{"text":"Hippocampal CA3 pyramidal neurons (PNs) form the largest autoassociative network in the mammalian brain. Whether CA3–CA3 recurrent connectivity is genetically preconfigured or environmentally shaped during ongoing memory storage is currently unknown. To address this question, we performed multicellular patch-clamp-based circuit mapping of up to eight CA3 PNs in the mouse hippocampus at multiple postnatal time points (P7–8, P18–25, and P45–50). Here, we show that the hippocampal CA3 network undergoes a developmental transformation from local, dense, and random connectivity to a distributed, sparse, and structured configuration. Thus, sparse and structured connectivity may emerge via experience-dependent mechanisms. In parallel, the strength of single synapses is downregulated; single synaptic events are sufficient to trigger postsynaptic spiking early in development, whereas spatial summation of several inputs is required at later time points. Biologically inspired models of memory storage by Hebbian synaptic plasticity and retrieval via pattern completion suggest that developmental changes improve specific aspects of memory storage and retrieval. Our results imply a developmental transformation of the neuronal code and the memory functions in the hippocampal CA3 network.</jats:p>","lang":"eng"}],"das_tickbox":"1","status":"public","day":"23","article_type":"original","file":[{"success":1,"file_id":"22231","file_size":18304997,"access_level":"open_access","creator":"dernst","relation":"main_file","file_name":"2026_NatureComm_VargasBarroso.pdf","checksum":"d0b0093493926985b4c268662ff4d556","date_updated":"2026-07-01T06:46:06Z","content_type":"application/pdf","date_created":"2026-07-01T06:46:06Z"}],"has_accepted_license":"1","department":[{"_id":"PeJo"},{"_id":"ScienComp"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","doi":"10.1038/s41467-026-71914-x","quality_controlled":"1","date_published":"2026-06-23T00:00:00Z","scopus_import":"1","publisher":"Springer Nature","date_created":"2026-06-30T13:05:52Z","license":"https://creativecommons.org/licenses/by/4.0/","PlanS_conform":"1","dataavailabilitystatement":"Source data are provided with this paper. Additional original data are available from the corresponding author upon request. Code is available from https://doi.org/10.15479/AT-ISTA-21442 under the link https://research-explorer.ista.ac.at/download/21442/21443/ca3simu-vargas2026v1.tar.gz","type":"journal_article"},{"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.).","pmid":1,"ec_funded":1,"OA_place":"publisher","OA_type":"hybrid","related_material":{"record":[{"id":"18688","status":"public","relation":"earlier_version"}]},"date_updated":"2026-04-14T08:34:32Z","_id":"18879","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"ScienComp"}],"title":"Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory","intvolume":"       188","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"ddc":["570"],"oa":1,"month":"01","volume":188,"external_id":{"isi":["001408395600001"],"pmid":["39667938"]},"file_date_updated":"2025-01-27T08:46:33Z","author":[{"full_name":"Watson, Jake","last_name":"Watson","first_name":"Jake","orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"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"},{"full_name":"Navas Olivé, Andrea C","last_name":"Navas Olivé","first_name":"Andrea C","orcid":"0000-0002-9280-8597","id":"739d26c9-52e8-11ee-8d72-f14d3893b4ce"},{"last_name":"Tavakoli","full_name":"Tavakoli, Mojtaba","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7667-6854","first_name":"Mojtaba"},{"orcid":"0000-0001-8559-3973","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","last_name":"Danzl"},{"first_name":"Matthias","last_name":"Tomschik","full_name":"Tomschik, Matthias"},{"first_name":"Karl","last_name":"Rössler","full_name":"Rössler, Karl"},{"full_name":"Jonas, Peter M","last_name":"Jonas","first_name":"Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["0092-8674"],"eissn":["1097-4172"]},"publication":"Cell","publication_status":"published","citation":{"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>","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.","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.","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.","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>.","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>","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>."},"year":"2025","article_processing_charge":"Yes (via OA deal)","corr_author":"1","oa_version":"Published Version","page":"501-514.e18","project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","call_identifier":"H2020"},{"grant_number":"101026635","call_identifier":"H2020","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","name":"Synaptic computations of the hippocampal CA3 circuitry"},{"_id":"6285a163-2b32-11ec-9570-8e204ca2dba5","name":"Studying Organelle Structure and Function at Nanoscale Resolution with Expansion Microscopy","grant_number":"26137"},{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","name":"Molecular Drug Targets","call_identifier":"FWF","grant_number":"W1232"},{"_id":"8d9195e9-16d5-11f0-9cad-d075be887a1e","name":"Synaptic networks of human brain","grant_number":"PAT 4178023"},{"_id":"9B861AAC-BA93-11EA-9121-9846C619BF3A","name":"NOMIS Fellowship Program"}],"date_created":"2025-01-26T23:01:49Z","publisher":"Elsevier","scopus_import":"1","date_published":"2025-01-23T00:00:00Z","quality_controlled":"1","type":"journal_article","issue":"2","doi":"10.1016/j.cell.2024.11.022","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"JoDa"},{"_id":"PeJo"},{"_id":"GradSch"}],"has_accepted_license":"1","file":[{"checksum":"d5a818edc32d249cdf75e1bb5b70a4b7","file_name":"2025_Cell_Watson.pdf","creator":"dernst","relation":"main_file","file_id":"18884","file_size":14082343,"access_level":"open_access","success":1,"date_created":"2025-01-27T08:46:33Z","content_type":"application/pdf","date_updated":"2025-01-27T08:46:33Z"}],"article_type":"original","isi":1,"day":"23","status":"public","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. "}]},{"isi":1,"day":"01","status":"public","abstract":[{"lang":"eng","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."}],"scopus_import":"1","publisher":"Elsevier","date_created":"2025-08-03T22:01:30Z","date_published":"2025-08-01T00:00:00Z","quality_controlled":"1","issue":"8","type":"journal_article","PlanS_conform":"1","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","doi":"10.1016/j.celrep.2025.116080","article_type":"original","file":[{"relation":"main_file","creator":"dernst","checksum":"556ff9760661ecd23949d75031043b1f","file_name":"2025_CellReports_Watson.pdf","success":1,"access_level":"open_access","file_size":27695214,"file_id":"20106","date_created":"2025-08-04T06:53:07Z","date_updated":"2025-08-04T06:53:07Z","content_type":"application/pdf"}],"department":[{"_id":"PeJo"}],"has_accepted_license":"1","author":[{"orcid":"0000-0002-8698-3823","first_name":"Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","full_name":"Watson, Jake","last_name":"Watson"},{"last_name":"Vargas Barroso","full_name":"Vargas Barroso, Victor M","id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87","first_name":"Victor M"},{"orcid":"0000-0001-5001-4804","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","last_name":"Jonas"}],"DOAJ_listed":"1","file_date_updated":"2025-08-04T06:53:07Z","publication_identifier":{"eissn":["2211-1247"],"issn":["2639-1856"]},"language":[{"iso":"eng"}],"publication":"Cell Reports","citation":{"ista":"Watson J, Vargas Barroso VM, Jonas PM. 2025. Cell-specific wiring routes information flow through hippocampal CA3. Cell Reports. 44(8), 116080.","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>","short":"J. Watson, V.M. Vargas Barroso, P.M. Jonas, Cell Reports 44 (2025).","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.","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>.","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>.","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>"},"publication_status":"published","article_number":"116080","year":"2025","article_processing_charge":"Yes","oa_version":"Published Version","corr_author":"1","project":[{"call_identifier":"H2020","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"grant_number":"101026635","call_identifier":"H2020","name":"Synaptic computations of the hippocampal CA3 circuitry","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9"},{"name":"Mechanisms of GABA release in hippocampal circuits","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","grant_number":"P36232"},{"grant_number":"754411","call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","_id":"260C2330-B435-11E9-9278-68D0E5697425"}],"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.).","OA_place":"publisher","OA_type":"gold","ec_funded":1,"date_updated":"2025-09-30T14:12:02Z","_id":"20099","intvolume":"        44","title":"Cell-specific wiring routes information flow through hippocampal CA3","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"ddc":["570"],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"volume":44,"month":"08","oa":1,"external_id":{"isi":["001544472300002"]}},{"department":[{"_id":"PeJo"}],"has_accepted_license":"1","article_type":"original","file":[{"date_created":"2023-02-06T07:56:14Z","date_updated":"2023-02-06T07:56:14Z","content_type":"application/pdf","creator":"dernst","relation":"main_file","file_name":"2022_FrontiersNeuroanatomy_OrtizLeal.pdf","checksum":"49cd40f3bda6f267079427042e7d15e3","success":1,"access_level":"open_access","file_id":"12518","file_size":21943473}],"doi":"10.3389/fnana.2022.1097467","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_published":"2023-01-10T00:00:00Z","quality_controlled":"1","date_created":"2023-02-05T23:01:00Z","publisher":"Frontiers","scopus_import":"1","type":"journal_article","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"}],"status":"public","isi":1,"day":"10","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"ddc":["570"],"title":"The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway","intvolume":"        16","external_id":{"isi":["000919786900001"],"pmid":["36704406"]},"oa":1,"volume":16,"month":"01","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.","pmid":1,"_id":"12515","date_updated":"2023-08-16T11:37:52Z","article_processing_charge":"No","year":"2023","oa_version":"Published Version","language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1662-5129"]},"file_date_updated":"2023-02-06T07:56:14Z","author":[{"first_name":"Irene","full_name":"Ortiz-Leal, Irene","last_name":"Ortiz-Leal"},{"first_name":"Mateo V.","last_name":"Torres","full_name":"Torres, Mateo V."},{"id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87","first_name":"Victor M","last_name":"Vargas Barroso","full_name":"Vargas Barroso, Victor M"},{"full_name":"Fidalgo, Luis Eusebio","last_name":"Fidalgo","first_name":"Luis Eusebio"},{"full_name":"López-Beceiro, Ana María","last_name":"López-Beceiro","first_name":"Ana María"},{"first_name":"Jorge A.","last_name":"Larriva-Sahd","full_name":"Larriva-Sahd, Jorge A."},{"last_name":"Sánchez-Quinteiro","full_name":"Sánchez-Quinteiro, Pablo","first_name":"Pablo"}],"article_number":"1097467","publication_status":"published","citation":{"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>","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>.","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).","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.","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.","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>"},"publication":"Frontiers in Neuroanatomy"},{"isi":1,"day":"01","status":"public","abstract":[{"text":"Rigorous investigation of synaptic transmission requires analysis of unitary synaptic events by simultaneous recording from presynaptic terminals and postsynaptic target neurons. However, this has been achieved at only a limited number of model synapses, including the squid giant synapse and the mammalian calyx of Held. Cortical presynaptic terminals have been largely inaccessible to direct presynaptic recording, due to their small size. Here, we describe a protocol for improved subcellular patch-clamp recording in rat and mouse brain slices, with the synapse in a largely intact environment. Slice preparation takes ~2 h, recording ~3 h and post hoc morphological analysis 2 d. Single presynaptic hippocampal mossy fiber terminals are stimulated minimally invasively in the bouton-attached configuration, in which the cytoplasmic content remains unperturbed, or in the whole-bouton configuration, in which the cytoplasmic composition can be precisely controlled. Paired pre–postsynaptic recordings can be integrated with biocytin labeling and morphological analysis, allowing correlative investigation of synapse structure and function. Paired recordings can be obtained from mossy fiber terminals in slices from both rats and mice, implying applicability to genetically modified synapses. Paired recordings can also be performed together with axon tract stimulation or optogenetic activation, allowing comparison of unitary and compound synaptic events in the same target cell. Finally, paired recordings can be combined with spontaneous event analysis, permitting collection of miniature events generated at a single identified synapse. In conclusion, the subcellular patch-clamp techniques detailed here should facilitate analysis of biophysics, plasticity and circuit function of cortical synapses in the mammalian central nervous system.","lang":"eng"}],"publisher":"Springer Nature","date_created":"2021-05-30T22:01:24Z","scopus_import":"1","quality_controlled":"1","date_published":"2021-06-01T00:00:00Z","type":"journal_article","issue":"6","doi":"10.1038/s41596-021-00526-0","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"PeJo"}],"has_accepted_license":"1","article_type":"original","file":[{"date_created":"2021-07-08T12:27:55Z","content_type":"application/pdf","date_updated":"2021-12-02T23:30:05Z","embargo":"2021-12-01","checksum":"7eb580abd8893cdb0b410cf41bc8c263","file_name":"VandaeletalAuthorVersion2021.pdf","creator":"cziletti","relation":"main_file","access_level":"open_access","file_size":38574802,"file_id":"9639"}],"file_date_updated":"2021-12-02T23:30:05Z","author":[{"full_name":"Vandael, David H","last_name":"Vandael","orcid":"0000-0001-7577-1676","first_name":"David H","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-0408-6094","first_name":"Yuji","id":"3337E116-F248-11E8-B48F-1D18A9856A87","full_name":"Okamoto, Yuji","last_name":"Okamoto"},{"orcid":"0000-0003-0005-401X","first_name":"Carolina","id":"4305C450-F248-11E8-B48F-1D18A9856A87","full_name":"Borges Merjane, Carolina","last_name":"Borges Merjane"},{"last_name":"Vargas Barroso","full_name":"Vargas Barroso, Victor M","id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87","first_name":"Victor M"},{"orcid":"0000-0002-9885-6936","first_name":"Benjamin","id":"4952F31E-F248-11E8-B48F-1D18A9856A87","full_name":"Suter, Benjamin","last_name":"Suter"},{"first_name":"Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","last_name":"Jonas"}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1750-2799"],"issn":["1754-2189"]},"publication":"Nature Protocols","publication_status":"published","citation":{"ieee":"D. H. Vandael, Y. Okamoto, C. Borges Merjane, V. M. Vargas Barroso, B. Suter, and P. M. Jonas, “Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses,” <i>Nature Protocols</i>, vol. 16, no. 6. Springer Nature, pp. 2947–2967, 2021.","short":"D.H. Vandael, Y. Okamoto, C. Borges Merjane, V.M. Vargas Barroso, B. Suter, P.M. Jonas, Nature Protocols 16 (2021) 2947–2967.","ista":"Vandael DH, Okamoto Y, Borges Merjane C, Vargas Barroso VM, Suter B, Jonas PM. 2021. Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses. Nature Protocols. 16(6), 2947–2967.","apa":"Vandael, D. H., Okamoto, Y., Borges Merjane, C., Vargas Barroso, V. M., Suter, B., &#38; Jonas, P. M. (2021). Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses. <i>Nature Protocols</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41596-021-00526-0\">https://doi.org/10.1038/s41596-021-00526-0</a>","ama":"Vandael DH, Okamoto Y, Borges Merjane C, Vargas Barroso VM, Suter B, Jonas PM. Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses. <i>Nature Protocols</i>. 2021;16(6):2947–2967. doi:<a href=\"https://doi.org/10.1038/s41596-021-00526-0\">10.1038/s41596-021-00526-0</a>","chicago":"Vandael, David H, Yuji Okamoto, Carolina Borges Merjane, Victor M Vargas Barroso, Benjamin Suter, and Peter M Jonas. “Subcellular Patch-Clamp Techniques for Single-Bouton Stimulation and Simultaneous Pre- and Postsynaptic Recording at Cortical Synapses.” <i>Nature Protocols</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41596-021-00526-0\">https://doi.org/10.1038/s41596-021-00526-0</a>.","mla":"Vandael, David H., et al. “Subcellular Patch-Clamp Techniques for Single-Bouton Stimulation and Simultaneous Pre- and Postsynaptic Recording at Cortical Synapses.” <i>Nature Protocols</i>, vol. 16, no. 6, Springer Nature, 2021, pp. 2947–2967, doi:<a href=\"https://doi.org/10.1038/s41596-021-00526-0\">10.1038/s41596-021-00526-0</a>."},"year":"2021","article_processing_charge":"No","oa_version":"Submitted Version","corr_author":"1","page":"2947–2967","project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"Synaptic communication in neuronal microcircuits","grant_number":"Z00312","call_identifier":"FWF"},{"call_identifier":"FWF","grant_number":"V00739","name":"Structural plasticity at mossy fiber-CA3 synapses","_id":"2696E7FE-B435-11E9-9278-68D0E5697425"}],"acknowledgement":"This project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award to P.J., V 739-B27 to C.B.M.). We are grateful to F. Marr and C. Altmutter for excellent technical assistance and cell reconstruction, E. Kralli-Beller for manuscript editing, and the Scientific Service Units of IST Austria, especially T. Asenov and Miba machine shop, for maximally efficient support.","pmid":1,"ec_funded":1,"date_updated":"2025-04-22T22:30:43Z","_id":"9438","acknowledged_ssus":[{"_id":"M-Shop"}],"title":"Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses","intvolume":"        16","ddc":["570"],"oa":1,"month":"06","volume":16,"external_id":{"pmid":["33990799"],"isi":["000650528700003"]}}]
