{"publication":"Cell","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)"},"file_date_updated":"2025-01-27T08:46:33Z","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."}],"day":"23","scopus_import":"1","date_updated":"2025-01-27T08:56:57Z","article_processing_charge":"Yes (via OA deal)","corr_author":"1","publication_identifier":{"issn":["0092-8674"],"eissn":["1097-4172"]},"related_material":{"record":[{"status":"public","relation":"earlier_version","id":"18688"}]},"title":"Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory","year":"2025","date_created":"2025-01-26T23:01:49Z","citation":{"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>.","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.","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.","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>.","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>"},"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.).","language":[{"iso":"eng"}],"publication_status":"published","file":[{"date_updated":"2025-01-27T08:46:33Z","checksum":"d5a818edc32d249cdf75e1bb5b70a4b7","success":1,"content_type":"application/pdf","access_level":"open_access","file_size":14082343,"file_name":"2025_Cell_Watson.pdf","relation":"main_file","creator":"dernst","file_id":"18884","date_created":"2025-01-27T08:46:33Z"}],"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":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","name":"Synaptic computations of the hippocampal CA3 circuitry","call_identifier":"H2020","grant_number":"101026635"},{"_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-B24"}],"article_type":"original","OA_type":"hybrid","doi":"10.1016/j.cell.2024.11.022","month":"01","license":"https://creativecommons.org/licenses/by/4.0/","intvolume":"       188","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"ScienComp"}],"issue":"2","department":[{"_id":"JoDa"},{"_id":"PeJo"},{"_id":"GradSch"}],"page":"501-514.e18","date_published":"2025-01-23T00:00:00Z","quality_controlled":"1","ec_funded":1,"ddc":["570"],"volume":188,"author":[{"last_name":"Watson","full_name":"Watson, Jake","orcid":"0000-0002-8698-3823","first_name":"Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"first_name":"Victor M","id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87","full_name":"Vargas Barroso, Victor M","last_name":"Vargas Barroso"},{"id":"ceb89ae7-dc8d-11ea-abe3-da3301d0eab4","first_name":"Rebecca","full_name":"Morse, Rebecca","last_name":"Morse"},{"orcid":"0000-0002-9280-8597","last_name":"Navas Olivé","full_name":"Navas Olivé, Andrea C","first_name":"Andrea C","id":"739d26c9-52e8-11ee-8d72-f14d3893b4ce"},{"orcid":"0000-0002-7667-6854","full_name":"Tavakoli, Mojtaba","last_name":"Tavakoli","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","first_name":"Mojtaba"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G","last_name":"Danzl","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973"},{"first_name":"Matthias","full_name":"Tomschik, Matthias","last_name":"Tomschik"},{"first_name":"Karl","last_name":"Rössler","full_name":"Rössler, Karl"},{"first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","last_name":"Jonas","full_name":"Jonas, Peter M"}],"OA_place":"publisher","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","has_accepted_license":"1","publisher":"Elsevier","oa_version":"Published Version","type":"journal_article","status":"public","_id":"18879","oa":1}