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Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s41467-026-71914-x\">https://doi.org/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.","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>.","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>"},"oa_version":"Published Version","publication_identifier":{"eissn":["2041-1723"]},"doi":"10.1038/s41467-026-71914-x","article_processing_charge":"Yes","publication_status":"published","date_created":"2026-06-30T13:05:52Z","external_id":{"pmid":["42014695"]},"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","orcid":"0000-0002-8698-3823","full_name":"Watson, Jake","first_name":"Jake","last_name":"Watson"},{"last_name":"Navas Olivé","id":"739d26c9-52e8-11ee-8d72-f14d3893b4ce","orcid":"0000-0002-9280-8597","first_name":"Andrea C","full_name":"Navas Olivé, Andrea C"},{"last_name":"Schlögl","full_name":"Schlögl, Alois","first_name":"Alois","orcid":"0000-0002-5621-8100","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Jonas, Peter M","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","last_name":"Jonas"}],"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"}],"file_date_updated":"2026-07-01T06:46:06Z","article_number":"5540","article_type":"original","title":"Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit","_id":"22229","supplementarymaterial":"yes","publisher":"Springer Nature","month":"06","volume":17,"oa":1,"OA_place":"publisher","date_published":"2026-06-23T00:00:00Z","das_tickbox":"1","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"M-Shop"},{"_id":"ScienComp"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"year":"2026","file":[{"success":1,"file_size":18304997,"date_created":"2026-07-01T06:46:06Z","access_level":"open_access","file_id":"22231","checksum":"d0b0093493926985b4c268662ff4d556","date_updated":"2026-07-01T06:46:06Z","content_type":"application/pdf","file_name":"2026_NatureComm_VargasBarroso.pdf","relation":"main_file","creator":"dernst"}],"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","department":[{"_id":"PeJo"},{"_id":"ScienComp"}],"quality_controlled":"1","OA_type":"gold","researchdata_availability":"yes","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).","scopus_import":"1","ddc":["570"],"date_updated":"2026-07-01T06:47:49Z","day":"23","fulldoi":"https://doi.org/10.1038/s41467-026-71914-x","pmid":1,"project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","grant_number":"692692","call_identifier":"H2020"},{"grant_number":"101199096","name":"Synaptic mechanisms of engram storage and retrieval in CA3 hippocampal microcircuits","_id":"e62b56fe-ab3c-11f0-94c7-d181dd352b3b"},{"_id":"260C2330-B435-11E9-9278-68D0E5697425","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","call_identifier":"H2020"},{"_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","grant_number":"101026635","name":"Synaptic computations of the hippocampal CA3 circuitry","call_identifier":"H2020"},{"name":"Mechanisms of GABA release in hippocampal circuits","grant_number":"P36232","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5"},{"_id":"8d9195e9-16d5-11f0-9cad-d075be887a1e","name":"Synaptic networks of human brain","grant_number":"PAT 4178023"},{"_id":"26366136-B435-11E9-9278-68D0E5697425","name":"Reglas de Conectividad funcional en el hipocampo"}],"ec_funded":1,"type":"journal_article","status":"public","has_accepted_license":"1"},{"ec_funded":1,"date_published":"2026-03-12T00:00:00Z","project":[{"_id":"e62b56fe-ab3c-11f0-94c7-d181dd352b3b","name":"Synaptic mechanisms of engram storage and retrieval in CA3 hippocampal microcircuits","grant_number":"101199096"},{"_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","grant_number":"P36232","name":"Mechanisms of GABA release in hippocampal circuits"},{"_id":"8d9195e9-16d5-11f0-9cad-d075be887a1e","grant_number":"PAT 4178023","name":"Synaptic networks of human brain"},{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"}],"oa":1,"month":"03","has_accepted_license":"1","status":"public","tmp":{"legal_code_url":"https://www.gnu.org/licenses/gpl-3.0.en.html","short":"GPL 3.0","name":"GNU General Public License 3.0"},"license":"https://opensource.org/licenses/GPL-3.0","type":"software","title":"CA3Simu v1.06 (vargas2026v1)","publisher":"Institute of Science and Technology Austria","fulldoi":"https://doi.org/10.15479/AT-ISTA-21442","date_updated":"2026-07-01T06:47:49Z","_id":"21442","day":"12","doi":"10.15479/AT-ISTA-21442","date_created":"2026-03-12T08:20:46Z","keyword":["hypocampus","ca3 simulations","modelling"],"file_date_updated":"2026-03-12T10:24:45Z","author":[{"last_name":"Schlögl","orcid":"0000-0002-5621-8100","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","full_name":"Schlögl, Alois","first_name":"Alois"}],"related_material":{"record":[{"relation":"used_in_publication","id":"22229","status":"public"}]},"department":[{"_id":"ScienComp"},{"_id":"PeJo"}],"file":[{"success":1,"file_size":160410,"access_level":"open_access","date_created":"2026-03-12T08:19:14Z","file_id":"21443","checksum":"441c8827717dcda05f91c127d15cf1e9","date_updated":"2026-03-12T08:19:14Z","content_type":"application/gzip","relation":"main_file","file_name":"ca3simu-vargas2026v1.tar.gz","creator":"schloegl"},{"checksum":"3c0092076228a15c0a7ae703192d43ea","date_created":"2026-03-12T10:24:45Z","access_level":"open_access","file_id":"21445","file_size":10923,"success":1,"creator":"schloegl","relation":"main_file","file_name":"README.md","content_type":"text/markdown","date_updated":"2026-03-12T10:24:45Z"}],"corr_author":"1","user_id":"68b8ca59-c5b3-11ee-8790-cd641c68093d","year":"2026","citation":{"mla":"Schlögl, Alois. <i>CA3Simu v1.06 (Vargas2026v1)</i>. 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Lin, “Calibrating the teacher synapse: Mechanisms and functional significance of presynaptic inhibition at hippocampal mossy fiber synapses,” Institute of Science and Technology Austria, 2026.","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.","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>."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","corr_author":"1","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"PreCl"},{"_id":"Bio"}],"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)"},"month":"08","date_published":"2026-08-25T00:00:00Z","das_tickbox":"0","OA_place":"publisher","supplementarymaterial":"yes","_id":"22735","publisher":"Institute of Science and Technology Austria","title":"Calibrating the teacher synapse: Mechanisms and functional significance of presynaptic inhibition at hippocampal mossy fiber synapses","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.).","researchdata_availability":"upon 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(2026). <i>Timing and strength of synaptic transmission at hippocampal mossy fiber synapses in mice and humans</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-22775\">https://doi.org/10.15479/AT-ISTA-22775</a>","mla":"Jamrichova, Silvia. <i>Timing and Strength of Synaptic Transmission at Hippocampal Mossy Fiber Synapses in Mice and Humans</i>. Institute of Science and Technology Austria, 2026, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-22775\">10.15479/AT-ISTA-22775</a>.","ista":"Jamrichova S. 2026. Timing and strength of synaptic transmission at hippocampal mossy fiber synapses in mice and humans. Institute of Science and Technology Austria.","chicago":"Jamrichova, Silvia. “Timing and Strength of Synaptic Transmission at Hippocampal Mossy Fiber Synapses in Mice and Humans.” Institute of Science and Technology Austria, 2026. <a href=\"https://doi.org/10.15479/AT-ISTA-22775\">https://doi.org/10.15479/AT-ISTA-22775</a>.","ieee":"S. Jamrichova, “Timing and strength of synaptic transmission at hippocampal mossy fiber synapses in mice and humans,” Institute of Science and Technology Austria, 2026.","short":"S. Jamrichova, Timing and Strength of Synaptic Transmission at Hippocampal Mossy Fiber Synapses in Mice and Humans, Institute of Science and Technology Austria, 2026.","ama":"Jamrichova S. Timing and strength of synaptic transmission at hippocampal mossy fiber synapses in mice and humans. 2026. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-22775\">10.15479/AT-ISTA-22775</a>"},"oa_version":"Published Version","publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-085-5"]},"date_created":"2026-09-03T08:06:58Z","publication_status":"published","doi":"10.15479/AT-ISTA-22775","article_processing_charge":"No","author":[{"last_name":"Jamrichova","id":"F0EA6804-AA27-11E9-8613-C0F7E5697425","orcid":"0009-0003-9929-8221","full_name":"Jamrichova, Silvia","first_name":"Silvia"}],"file_date_updated":"2026-09-08T09:02:52Z"}]