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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).","file_date_updated":"2026-07-01T06:46:06Z","article_type":"original","publication_identifier":{"eissn":["2041-1723"]},"related_material":{"record":[{"relation":"research_data","id":"21442","status":"public"}]},"researchdata_availability":"yes","title":"Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit","date_updated":"2026-07-01T06:47:49Z","author":[{"id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87","full_name":"Vargas Barroso, Victor M","first_name":"Victor M","last_name":"Vargas Barroso"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","full_name":"Watson, Jake","orcid":"0000-0002-8698-3823","last_name":"Watson","first_name":"Jake"},{"id":"739d26c9-52e8-11ee-8d72-f14d3893b4ce","full_name":"Navas Olivé, Andrea C","first_name":"Andrea C","orcid":"0000-0002-9280-8597","last_name":"Navas Olivé"},{"id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","full_name":"Schlögl, Alois","orcid":"0000-0002-5621-8100","last_name":"Schlögl","first_name":"Alois"},{"last_name":"Jonas","orcid":"0000-0001-5001-4804","first_name":"Peter M","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"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","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"doi":"10.1038/s41467-026-71914-x","citation":{"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.","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>.","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>","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>","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>.","short":"V.M. Vargas Barroso, J. Watson, A.C. Navas Olivé, A. Schlögl, P.M. Jonas, Nature Communications 17 (2026)."},"project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"_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","grant_number":"754411","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","name":"Synaptic computations of the hippocampal CA3 circuitry","grant_number":"101026635"},{"grant_number":"P36232","name":"Mechanisms of GABA release in hippocampal circuits","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5"},{"_id":"8d9195e9-16d5-11f0-9cad-d075be887a1e","name":"Synaptic networks of human brain","grant_number":"PAT 4178023"},{"name":"Reglas de Conectividad funcional en el hipocampo","_id":"26366136-B435-11E9-9278-68D0E5697425"}],"volume":17,"scopus_import":"1","department":[{"_id":"PeJo"},{"_id":"ScienComp"}],"quality_controlled":"1","oa_version":"Published Version","_id":"22229","oa":1,"ec_funded":1,"type":"journal_article","date_published":"2026-06-23T00:00:00Z","article_number":"5540","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file":[{"success":1,"file_id":"22231","date_updated":"2026-07-01T06:46:06Z","file_name":"2026_NatureComm_VargasBarroso.pdf","creator":"dernst","checksum":"d0b0093493926985b4c268662ff4d556","relation":"main_file","date_created":"2026-07-01T06:46:06Z","content_type":"application/pdf","access_level":"open_access","file_size":18304997}],"publication_status":"published","article_processing_charge":"Yes","year":"2026","intvolume":"        17","PlanS_conform":"1","language":[{"iso":"eng"}],"OA_type":"gold","supplementarymaterial":"yes","publisher":"Springer Nature","has_accepted_license":"1","pmid":1,"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"}],"date_created":"2026-06-30T13:05:52Z","status":"public","publication":"Nature Communications","corr_author":"1","month":"06","ddc":["570"],"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"M-Shop"},{"_id":"ScienComp"}],"das_tickbox":"1"},{"publisher":"Institute of Science and Technology Austria","date_created":"2026-03-12T08:20:46Z","has_accepted_license":"1","department":[{"_id":"ScienComp"},{"_id":"PeJo"}],"tmp":{"legal_code_url":"https://www.gnu.org/licenses/gpl-3.0.en.html","name":"GNU General Public License 3.0","short":"GPL 3.0"},"doi":"10.15479/AT-ISTA-21442","citation":{"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>.","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>","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>","ieee":"A. Schlögl, “CA3Simu v1.06 (vargas2026v1).” Institute of Science and Technology Austria, 2026.","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>.","short":"A. Schlögl, (2026).","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>."},"project":[{"_id":"e62b56fe-ab3c-11f0-94c7-d181dd352b3b","name":"Synaptic mechanisms of engram storage and retrieval in CA3 hippocampal microcircuits","grant_number":"101199096"},{"grant_number":"P36232","name":"Mechanisms of GABA release in hippocampal circuits","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5"},{"_id":"8d9195e9-16d5-11f0-9cad-d075be887a1e","name":"Synaptic networks of human brain","grant_number":"PAT 4178023"},{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"}],"status":"public","month":"03","corr_author":"1","_id":"21442","day":"12","related_material":{"record":[{"relation":"used_in_publication","id":"22229","status":"public"}]},"file_date_updated":"2026-03-12T10:24:45Z","oa":1,"type":"software","license":"https://opensource.org/licenses/GPL-3.0","ec_funded":1,"author":[{"orcid":"0000-0002-5621-8100","last_name":"Schlögl","first_name":"Alois","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","full_name":"Schlögl, Alois"}],"file":[{"file_id":"21443","success":1,"date_updated":"2026-03-12T08:19:14Z","date_created":"2026-03-12T08:19:14Z","relation":"main_file","creator":"schloegl","checksum":"441c8827717dcda05f91c127d15cf1e9","file_name":"ca3simu-vargas2026v1.tar.gz","file_size":160410,"access_level":"open_access","content_type":"application/gzip"},{"file_size":10923,"access_level":"open_access","content_type":"text/markdown","date_created":"2026-03-12T10:24:45Z","relation":"main_file","creator":"schloegl","file_name":"README.md","checksum":"3c0092076228a15c0a7ae703192d43ea","date_updated":"2026-03-12T10:24:45Z","success":1,"file_id":"21445"}],"year":"2026","keyword":["hypocampus","ca3 simulations","modelling"],"title":"CA3Simu v1.06 (vargas2026v1)","date_updated":"2026-07-01T06:47:49Z","date_published":"2026-03-12T00:00:00Z","user_id":"68b8ca59-c5b3-11ee-8790-cd641c68093d"},{"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"PreCl"},{"_id":"Bio"}],"corr_author":"1","status":"public","month":"08","ddc":["571","573"],"das_tickbox":"0","degree_awarded":"PhD","supervisor":[{"first_name":"Peter M","last_name":"Jonas","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"language":[{"iso":"eng"}],"publisher":"Institute of Science and Technology Austria","supplementarymaterial":"yes","alternative_title":["ISTA Thesis"],"date_created":"2026-08-18T15:23:41Z","has_accepted_license":"1","date_published":"2026-08-25T00:00:00Z","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","file":[{"embargo":"2027-09-01","file_id":"22765","embargo_to":"open_access","date_updated":"2026-08-26T10:09:48Z","relation":"main_file","date_created":"2026-08-26T10:09:48Z","creator":"plin","file_name":"2026_Lin_Peipeng_Thesis.pdf","checksum":"13cc7ead72aad90a134f310b531c73cd","file_size":6376229,"content_type":"application/pdf","access_level":"closed"},{"file_size":17681883,"access_level":"closed","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","date_created":"2026-08-26T10:09:53Z","relation":"source_file","checksum":"8c9c1445a7df284377be1a8c9dadd7c5","file_name":"2026_Lin_Peipeng_Thesis.docx","creator":"plin","date_updated":"2026-08-26T10:09:53Z","file_id":"22766"}],"article_processing_charge":"No","year":"2026","publication_status":"published","ec_funded":1,"type":"dissertation","page":"88","doi_confirm":"1","oa_version":"Published Version","_id":"22735","tmp":{"image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)"},"doi":"10.15479/AT-ISTA-22735","citation":{"chicago":"Lin, Peipeng. “Calibrating the Teacher Synapse: Mechanisms and Functional Significance of Presynaptic Inhibition at Hippocampal Mossy Fiber Synapses.” Institute of Science and Technology Austria, 2026. <a href=\"https://doi.org/10.15479/AT-ISTA-22735\">https://doi.org/10.15479/AT-ISTA-22735</a>.","short":"P. Lin, Calibrating the Teacher Synapse: Mechanisms and Functional Significance of Presynaptic Inhibition at Hippocampal Mossy Fiber Synapses, Institute of Science and Technology Austria, 2026.","mla":"Lin, Peipeng. <i>Calibrating the Teacher Synapse: Mechanisms and Functional Significance of Presynaptic Inhibition at Hippocampal Mossy Fiber Synapses</i>. Institute of Science and Technology Austria, 2026, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-22735\">10.15479/AT-ISTA-22735</a>.","ieee":"P. Lin, “Calibrating the teacher synapse: Mechanisms and functional significance of presynaptic inhibition at hippocampal mossy fiber synapses,” Institute of Science and Technology Austria, 2026.","ama":"Lin P. Calibrating the teacher synapse: Mechanisms and functional significance of presynaptic inhibition at hippocampal mossy fiber synapses. 2026. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-22735\">10.15479/AT-ISTA-22735</a>","apa":"Lin, P. (2026). <i>Calibrating the teacher synapse: Mechanisms and functional significance of presynaptic inhibition at hippocampal mossy fiber synapses</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-22735\">https://doi.org/10.15479/AT-ISTA-22735</a>","ista":"Lin P. 2026. Calibrating the teacher synapse: Mechanisms and functional significance of presynaptic inhibition at hippocampal mossy fiber synapses. Institute of Science and Technology Austria."},"project":[{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","grant_number":"692692"},{"_id":"e62b56fe-ab3c-11f0-94c7-d181dd352b3b","grant_number":"101199096","name":"Synaptic mechanisms of engram storage and retrieval in CA3 hippocampal microcircuits"},{"_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","grant_number":"P36232","name":"Mechanisms of GABA release in hippocampal circuits"},{"name":"Synaptic networks of human brain","grant_number":"PAT 4178023","_id":"8d9195e9-16d5-11f0-9cad-d075be887a1e"},{"grant_number":"101034413","name":"IST-BRIDGE: International postdoctoral program","_id":"fc2ed2f7-9c52-11eb-aca3-c01059dda49c","call_identifier":"H2020"}],"department":[{"_id":"GradSch"},{"_id":"PeJo"}],"date_updated":"2026-08-31T11:11:55Z","researchdata_availability":"upon request","title":"Calibrating the teacher synapse: Mechanisms and functional significance of presynaptic inhibition at hippocampal mossy fiber synapses","author":[{"id":"7E3060D0-A92C-11E9-A326-26C8E5697425","full_name":"Lin, Peipeng","first_name":"Peipeng","last_name":"Lin"}],"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","OA_place":"publisher","publication_identifier":{"isbn":["978-3-99078-088-6"],"issn":["2663-337X"]},"file_date_updated":"2026-08-26T10:09:53Z","acknowledgement":"This project was supported by the following funding agencies: ERC under the European\r\nUnion's Horizon 2020 research and innovation program (ERC Advanced Grants No 692692\r\n“GIANTSYN” and 101199096 “CA3-SYNGRAM” to P.J.), the Fonds zur Förderung der\r\nwissenschaftlichen Forschung (P 36232-B, stand-alone grant, PAT 4178023, principal\r\ninvestigator project, and 10.55776/CoE 16 “GABA neurons” to P.J.), and the European Union’s\r\nHorizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant\r\nagreement (No 101034413, to K.L.).","day":"25"},{"tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"citation":{"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.","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>","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>","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>.","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.","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>."},"doi":"10.1016/j.cell.2024.11.022","project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"call_identifier":"H2020","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","name":"Synaptic computations of the hippocampal CA3 circuitry","grant_number":"101026635"},{"grant_number":"26137","name":"Studying Organelle Structure and Function at Nanoscale Resolution with Expansion Microscopy","_id":"6285a163-2b32-11ec-9570-8e204ca2dba5"},{"grant_number":"W1232","name":"Molecular Drug Targets","_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"_id":"8d9195e9-16d5-11f0-9cad-d075be887a1e","grant_number":"PAT 4178023","name":"Synaptic networks of human brain"},{"_id":"9B861AAC-BA93-11EA-9121-9846C619BF3A","name":"NOMIS Fellowship Program"}],"volume":188,"scopus_import":"1","department":[{"_id":"JoDa"},{"_id":"PeJo"},{"_id":"GradSch"}],"quality_controlled":"1","oa_version":"Published Version","_id":"18879","external_id":{"pmid":["39667938"],"isi":["001408395600001"]},"OA_place":"publisher","publication_identifier":{"issn":["0092-8674"],"eissn":["1097-4172"]},"article_type":"original","related_material":{"record":[{"status":"public","relation":"earlier_version","id":"18688"}]},"file_date_updated":"2025-01-27T08:46:33Z","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.).","day":"23","date_updated":"2026-04-14T08:34:32Z","title":"Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory","author":[{"first_name":"Jake","orcid":"0000-0002-8698-3823","last_name":"Watson","id":"63836096-4690-11EA-BD4E-32803DDC885E","full_name":"Watson, Jake"},{"full_name":"Vargas Barroso, Victor M","id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87","last_name":"Vargas Barroso","first_name":"Victor M"},{"id":"ceb89ae7-dc8d-11ea-abe3-da3301d0eab4","full_name":"Morse, Rebecca","first_name":"Rebecca","last_name":"Morse"},{"last_name":"Navas Olivé","orcid":"0000-0002-9280-8597","first_name":"Andrea C","full_name":"Navas Olivé, Andrea C","id":"739d26c9-52e8-11ee-8d72-f14d3893b4ce"},{"orcid":"0000-0002-7667-6854","last_name":"Tavakoli","first_name":"Mojtaba","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","full_name":"Tavakoli, Mojtaba"},{"first_name":"Johann G","orcid":"0000-0001-8559-3973","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G"},{"full_name":"Tomschik, Matthias","first_name":"Matthias","last_name":"Tomschik"},{"full_name":"Rössler, Karl","first_name":"Karl","last_name":"Rössler"},{"first_name":"Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M"}],"intvolume":"       188","OA_type":"hybrid","language":[{"iso":"eng"}],"publisher":"Elsevier","abstract":[{"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. ","lang":"eng"}],"has_accepted_license":"1","pmid":1,"date_created":"2025-01-26T23:01:49Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"ScienComp"}],"corr_author":"1","status":"public","ddc":["570"],"month":"01","publication":"Cell","issue":"2","oa":1,"isi":1,"ec_funded":1,"type":"journal_article","page":"501-514.e18","date_published":"2025-01-23T00:00:00Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file":[{"relation":"main_file","date_created":"2025-01-27T08:46:33Z","file_name":"2025_Cell_Watson.pdf","creator":"dernst","checksum":"d5a818edc32d249cdf75e1bb5b70a4b7","file_size":14082343,"content_type":"application/pdf","access_level":"open_access","success":1,"file_id":"18884","date_updated":"2025-01-27T08:46:33Z"}],"article_processing_charge":"Yes (via OA deal)","year":"2025","publication_status":"published"}]