[{"publication_status":"published","oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1038/s41592-023-01936-6"}],"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"E-Lib"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"date_published":"2023-08-01T00:00:00Z","status":"public","external_id":{"pmid":["37429995"],"isi":["001025621500001"]},"citation":{"apa":"Velicky, P., Miguel Villalba, E., Michalska, J. M., Lyudchik, J., Wei, D., Lin, Z., … Danzl, J. G. (2023). Dense 4D nanoscale reconstruction of living brain tissue. <i>Nature Methods</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41592-023-01936-6\">https://doi.org/10.1038/s41592-023-01936-6</a>","mla":"Velicky, Philipp, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” <i>Nature Methods</i>, vol. 20, Springer Nature, 2023, pp. 1256–65, doi:<a href=\"https://doi.org/10.1038/s41592-023-01936-6\">10.1038/s41592-023-01936-6</a>.","ista":"Velicky P, Miguel Villalba E, Michalska JM, Lyudchik J, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. 2023. Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. 20, 1256–1265.","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Dense 4D nanoscale reconstruction of living brain tissue. <i>Nature Methods</i>. 2023;20:1256-1265. doi:<a href=\"https://doi.org/10.1038/s41592-023-01936-6\">10.1038/s41592-023-01936-6</a>","short":"P. Velicky, E. Miguel Villalba, J.M. Michalska, J. Lyudchik, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, Nature Methods 20 (2023) 1256–1265.","chicago":"Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Julia Lyudchik, Donglai Wei, Zudi Lin, Jake Watson, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” <i>Nature Methods</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41592-023-01936-6\">https://doi.org/10.1038/s41592-023-01936-6</a>.","ieee":"P. Velicky <i>et al.</i>, “Dense 4D nanoscale reconstruction of living brain tissue,” <i>Nature Methods</i>, vol. 20. Springer Nature, pp. 1256–1265, 2023."},"related_material":{"link":[{"relation":"software","url":"https://github.com/danzllab/LIONESS"}],"record":[{"id":"12817","status":"public","relation":"research_data"},{"id":"14770","status":"public","relation":"shorter_version"}]},"intvolume":"        20","date_updated":"2024-01-10T08:37:48Z","abstract":[{"lang":"eng","text":"Three-dimensional (3D) reconstruction of living brain tissue down to an individual synapse level would create opportunities for decoding the dynamics and structure–function relationships of the brain’s complex and dense information processing network; however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise ratio and prohibitive light burden in optical imaging, whereas electron microscopy is inherently static. Here we solved these challenges by developing an integrated optical/machine-learning technology, LIONESS (live information-optimized nanoscopy enabling saturated segmentation). This leverages optical modifications to stimulated emission depletion microscopy in comprehensively, extracellularly labeled tissue and previous information on sample structure via machine learning to simultaneously achieve isotropic super-resolution, high signal-to-noise ratio and compatibility with living tissue. This allows dense deep-learning-based instance segmentation and 3D reconstruction at a synapse level, incorporating molecular, activity and morphodynamic information. LIONESS opens up avenues for studying the dynamic functional (nano-)architecture of living brain tissue."}],"type":"journal_article","month":"08","oa_version":"Published Version","page":"1256-1265","date_created":"2023-07-23T22:01:13Z","volume":20,"year":"2023","acknowledgement":"We thank J. Vorlaufer, N. Agudelo and A. Wartak for microscope maintenance and troubleshooting, C. Kreuzinger and A. Freeman for technical assistance, M. Šuplata for hardware control support and M. Cunha dos Santos for initial exploration of software. We\r\nthank P. Henderson for advice on deep-learning training and M. Sixt, S. Boyd and T. Weiss for discussions and critical reading of the manuscript. L. Lavis (Janelia Research Campus) generously provided the JF585-HaloTag ligand. We acknowledge expert support by IST\r\nAustria’s scientific computing, imaging and optics, preclinical, library and laboratory support facilities and by the Miba machine shop. We gratefully acknowledge funding by the following sources: Austrian Science Fund (F.W.F.) grant no. I3600-B27 (J.G.D.), grant no. DK W1232\r\n(J.G.D. and J.M.M.) and grant no. Z 312-B27, Wittgenstein award (P.J.); the Gesellschaft für Forschungsförderung NÖ grant no. LSC18-022 (J.G.D.); an ISTA Interdisciplinary project grant (J.G.D. and B.B.); the European Union’s Horizon 2020 research and innovation programme,\r\nMarie-Skłodowska Curie grant 665385 (J.M.M. and J.L.); the European Union’s Horizon 2020 research and innovation programme, European Research Council grant no. 715767, MATERIALIZABLE (B.B.); grant no. 715508, REVERSEAUTISM (G.N.); grant no. 695568, SYNNOVATE (S.G.N.G.); and grant no. 692692, GIANTSYN (P.J.); the Simons\r\nFoundation Autism Research Initiative grant no. 529085 (S.G.N.G.); the Wellcome Trust Technology Development grant no. 202932 (S.G.N.G.); the Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.);\r\nthe Human Frontier Science Program postdoctoral fellowship LT000557/2018 (W.J.); and the National Science Foundation grant no. IIS-1835231 (H.P.) and NCS-FO-2124179 (H.P.).","_id":"13267","publication_identifier":{"eissn":["1548-7105"],"issn":["1548-7091"]},"quality_controlled":"1","doi":"10.1038/s41592-023-01936-6","project":[{"call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600"},{"grant_number":"W1232-B24","_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Drug Targets"},{"name":"The Wittgenstein Prize","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312"},{"name":"High content imaging to decode human immune cell interactions in health and allergic disease","_id":"23889792-32DE-11EA-91FC-C7463DDC885E"},{"name":"International IST Doctoral Program","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385"},{"grant_number":"715767","name":"MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling","call_identifier":"H2020","_id":"24F9549A-B435-11E9-9278-68D0E5697425"},{"grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models"},{"name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692"},{"name":"Synaptic computations of the hippocampal CA3 circuitry","call_identifier":"H2020","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","grant_number":"101026635"},{"grant_number":"LT00057","name":"High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration","_id":"2668BFA0-B435-11E9-9278-68D0E5697425"}],"language":[{"iso":"eng"}],"isi":1,"day":"01","author":[{"first_name":"Philipp","last_name":"Velicky","full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-5665-0430","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","full_name":"Miguel Villalba, Eder","first_name":"Eder","last_name":"Miguel Villalba"},{"last_name":"Michalska","first_name":"Julia M","full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","last_name":"Lyudchik","first_name":"Julia"},{"first_name":"Donglai","last_name":"Wei","full_name":"Wei, Donglai"},{"last_name":"Lin","first_name":"Zudi","full_name":"Lin, Zudi"},{"first_name":"Jake","last_name":"Watson","full_name":"Watson, Jake","orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"last_name":"Troidl","first_name":"Jakob","full_name":"Troidl, Jakob"},{"full_name":"Beyer, Johanna","first_name":"Johanna","last_name":"Beyer"},{"id":"43DF3136-F248-11E8-B48F-1D18A9856A87","full_name":"Ben Simon, Yoav","first_name":"Yoav","last_name":"Ben Simon"},{"full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer","first_name":"Christoph M"},{"last_name":"Jahr","first_name":"Wiebke","full_name":"Jahr, Wiebke","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Cenameri","first_name":"Alban","full_name":"Cenameri, Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"first_name":"Johannes","last_name":"Broichhagen","full_name":"Broichhagen, Johannes"},{"first_name":"Seth G.N.","last_name":"Grant","full_name":"Grant, Seth G.N."},{"last_name":"Jonas","first_name":"Peter M","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804"},{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino"},{"first_name":"Hanspeter","last_name":"Pfister","full_name":"Pfister, Hanspeter"},{"id":"49876194-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6511-9385","full_name":"Bickel, Bernd","first_name":"Bernd","last_name":"Bickel"},{"full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","first_name":"Johann G"}],"title":"Dense 4D nanoscale reconstruction of living brain tissue","pmid":1,"department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"},{"_id":"Bio"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Springer Nature","scopus_import":"1","article_processing_charge":"Yes","ec_funded":1,"article_type":"original","publication":"Nature Methods"},{"language":[{"iso":"eng"}],"citation":{"ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction of living brain tissue. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>","ista":"Velicky P, Miguel Villalba E, Michalska JM, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. Saturated reconstruction of living brain tissue. bioRxiv, <a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>.","mla":"Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>.","apa":"Velicky, P., Miguel Villalba, E., Michalska, J. M., Wei, D., Lin, Z., Watson, J., … Danzl, J. G. (n.d.). Saturated reconstruction of living brain tissue. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2022.03.16.484431\">https://doi.org/10.1101/2022.03.16.484431</a>","ieee":"P. Velicky <i>et al.</i>, “Saturated reconstruction of living brain tissue,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","chicago":"Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Donglai Wei, Zudi Lin, Jake Watson, Jakob Troidl, et al. “Saturated Reconstruction of Living Brain Tissue.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2022.03.16.484431\">https://doi.org/10.1101/2022.03.16.484431</a>.","short":"P. Velicky, E. Miguel Villalba, J.M. Michalska, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, BioRxiv (n.d.)."},"related_material":{"record":[{"status":"public","id":"12470","relation":"dissertation_contains"}]},"status":"public","main_file_link":[{"url":"https://doi.org/10.1101/2022.03.16.484431","open_access":"1"}],"date_published":"2022-05-09T00:00:00Z","doi":"10.1101/2022.03.16.484431","oa":1,"publication_status":"submitted","article_processing_charge":"No","publication":"bioRxiv","_id":"11943","year":"2022","department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"}],"publisher":"Cold Spring Harbor Laboratory","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_created":"2022-08-23T11:07:59Z","title":"Saturated reconstruction of living brain tissue","date_updated":"2024-03-25T23:30:11Z","day":"09","abstract":[{"text":"Complex wiring between neurons underlies the information-processing network enabling all brain functions, including cognition and memory. For understanding how the network is structured, processes information, and changes over time, comprehensive visualization of the architecture of living brain tissue with its cellular and molecular components would open up major opportunities. However, electron microscopy (EM) provides nanometre-scale resolution required for full <jats:italic>in-silico</jats:italic> reconstruction<jats:sup>1–5</jats:sup>, yet is limited to fixed specimens and static representations. Light microscopy allows live observation, with super-resolution approaches<jats:sup>6–12</jats:sup> facilitating nanoscale visualization, but comprehensive 3D-reconstruction of living brain tissue has been hindered by tissue photo-burden, photobleaching, insufficient 3D-resolution, and inadequate signal-to-noise ratio (SNR). Here we demonstrate saturated reconstruction of living brain tissue. We developed an integrated imaging and analysis technology, adapting stimulated emission depletion (STED) microscopy<jats:sup>6,13</jats:sup> in extracellularly labelled tissue<jats:sup>14</jats:sup> for high SNR and near-isotropic resolution. Centrally, a two-stage deep-learning approach leveraged previously obtained information on sample structure to drastically reduce photo-burden and enable automated volumetric reconstruction down to single synapse level. Live reconstruction provides unbiased analysis of tissue architecture across time in relation to functional activity and targeted activation, and contextual understanding of molecular labelling. This adoptable technology will facilitate novel insights into the dynamic functional architecture of living brain tissue.","lang":"eng"}],"oa_version":"Preprint","month":"05","type":"preprint","author":[{"full_name":"Velicky, Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431","first_name":"Philipp","last_name":"Velicky"},{"last_name":"Miguel Villalba","first_name":"Eder","full_name":"Miguel Villalba, Eder","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5665-0430"},{"last_name":"Michalska","first_name":"Julia M","full_name":"Michalska, Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3862-1235"},{"full_name":"Wei, Donglai","first_name":"Donglai","last_name":"Wei"},{"first_name":"Zudi","last_name":"Lin","full_name":"Lin, Zudi"},{"first_name":"Jake","last_name":"Watson","orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E","full_name":"Watson, Jake"},{"last_name":"Troidl","first_name":"Jakob","full_name":"Troidl, Jakob"},{"first_name":"Johanna","last_name":"Beyer","full_name":"Beyer, Johanna"},{"first_name":"Yoav","last_name":"Ben Simon","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","full_name":"Ben Simon, Yoav"},{"first_name":"Christoph M","last_name":"Sommer","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Jahr, Wiebke","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","last_name":"Jahr","first_name":"Wiebke"},{"last_name":"Cenameri","first_name":"Alban","full_name":"Cenameri, Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"first_name":"Johannes","last_name":"Broichhagen","full_name":"Broichhagen, Johannes"},{"full_name":"Grant, Seth G. N.","last_name":"Grant","first_name":"Seth G. N."},{"first_name":"Peter M","last_name":"Jonas","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia"},{"full_name":"Pfister, Hanspeter","last_name":"Pfister","first_name":"Hanspeter"},{"last_name":"Bickel","first_name":"Bernd","full_name":"Bickel, Bernd","orcid":"0000-0001-6511-9385","id":"49876194-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Johann G","last_name":"Danzl","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G"}]},{"quality_controlled":"1","doi":"10.1038/s41467-022-32559-8","publication_identifier":{"issn":["2041-1723"]},"language":[{"iso":"eng"}],"isi":1,"keyword":["General Physics and Astronomy","General Biochemistry","Genetics and Molecular Biology","General Chemistry","Multidisciplinary"],"project":[{"name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692"},{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600"},{"name":"The Wittgenstein Prize","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Z00312"}],"title":"A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory","article_number":"4826","day":"16","file":[{"file_id":"11990","date_updated":"2022-08-26T11:51:40Z","checksum":"405936d9e4d33625d80c093c9713a91f","date_created":"2022-08-26T11:51:40Z","access_level":"open_access","file_name":"2022_NatureCommunications_BenSimon.pdf","success":1,"file_size":5910357,"content_type":"application/pdf","relation":"main_file","creator":"dernst"}],"author":[{"full_name":"Ben Simon, Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","first_name":"Yoav","last_name":"Ben Simon"},{"last_name":"Käfer","first_name":"Karola","full_name":"Käfer, Karola","id":"2DAA49AA-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Velicky","first_name":"Philipp","full_name":"Velicky, Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431"},{"full_name":"Csicsvari, Jozsef L","orcid":"0000-0002-5193-4036","id":"3FA14672-F248-11E8-B48F-1D18A9856A87","last_name":"Csicsvari","first_name":"Jozsef L"},{"orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","last_name":"Danzl","first_name":"Johann G"},{"last_name":"Jonas","first_name":"Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M"}],"article_processing_charge":"No","ec_funded":1,"article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"publication":"Nature Communications","department":[{"_id":"JoCs"},{"_id":"PeJo"},{"_id":"JoDa"}],"publisher":"Springer Nature","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","acknowledged_ssus":[{"_id":"Bio"},{"_id":"SSU"}],"ddc":["570"],"date_published":"2022-08-16T00:00:00Z","has_accepted_license":"1","publication_status":"published","oa":1,"citation":{"short":"Y. Ben Simon, K. Käfer, P. Velicky, J.L. Csicsvari, J.G. Danzl, P.M. Jonas, Nature Communications 13 (2022).","ieee":"Y. Ben Simon, K. Käfer, P. Velicky, J. L. Csicsvari, J. G. Danzl, and P. M. Jonas, “A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory,” <i>Nature Communications</i>, vol. 13. Springer Nature, 2022.","chicago":"Ben Simon, Yoav, Karola Käfer, Philipp Velicky, Jozsef L Csicsvari, Johann G Danzl, and Peter M Jonas. “A Direct Excitatory Projection from Entorhinal Layer 6b Neurons to the Hippocampus Contributes to Spatial Coding and Memory.” <i>Nature Communications</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41467-022-32559-8\">https://doi.org/10.1038/s41467-022-32559-8</a>.","mla":"Ben Simon, Yoav, et al. “A Direct Excitatory Projection from Entorhinal Layer 6b Neurons to the Hippocampus Contributes to Spatial Coding and Memory.” <i>Nature Communications</i>, vol. 13, 4826, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s41467-022-32559-8\">10.1038/s41467-022-32559-8</a>.","ista":"Ben Simon Y, Käfer K, Velicky P, Csicsvari JL, Danzl JG, Jonas PM. 2022. A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory. Nature Communications. 13, 4826.","apa":"Ben Simon, Y., Käfer, K., Velicky, P., Csicsvari, J. L., Danzl, J. G., &#38; Jonas, P. M. (2022). A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-022-32559-8\">https://doi.org/10.1038/s41467-022-32559-8</a>","ama":"Ben Simon Y, Käfer K, Velicky P, Csicsvari JL, Danzl JG, Jonas PM. A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory. <i>Nature Communications</i>. 2022;13. doi:<a href=\"https://doi.org/10.1038/s41467-022-32559-8\">10.1038/s41467-022-32559-8</a>"},"intvolume":"        13","external_id":{"isi":["000841396400008"]},"status":"public","file_date_updated":"2022-08-26T11:51:40Z","date_created":"2022-08-24T08:25:50Z","volume":13,"abstract":[{"text":"The mammalian hippocampal formation (HF) plays a key role in several higher brain functions, such as spatial coding, learning and memory. Its simple circuit architecture is often viewed as a trisynaptic loop, processing input originating from the superficial layers of the entorhinal cortex (EC) and sending it back to its deeper layers. Here, we show that excitatory neurons in layer 6b of the mouse EC project to all sub-regions comprising the HF and receive input from the CA1, thalamus and claustrum. Furthermore, their output is characterized by unique slow-decaying excitatory postsynaptic currents capable of driving plateau-like potentials in their postsynaptic targets. Optogenetic inhibition of the EC-6b pathway affects spatial coding in CA1 pyramidal neurons, while cell ablation impairs not only acquisition of new spatial memories, but also degradation of previously acquired ones. Our results provide evidence of a functional role for cortical layer 6b neurons in the adult brain.","lang":"eng"}],"date_updated":"2023-08-03T13:01:19Z","oa_version":"Published Version","month":"08","type":"journal_article","_id":"11951","year":"2022","acknowledgement":"We thank F. Marr and A. Schlögl for technical assistance, E. Kralli-Beller for manuscript editing, as well as C. Sommer and the Imaging and Optics Facility of the Institute of Science and Technology Austria (ISTA) for image analysis scripts and microscopy support. We extend our gratitude to J. Wallenschus and D. Rangel Guerrero for technical assistance acquiring single-unit data and I. Gridchyn for help with single-unit clustering. Finally, we also thank B. Suter for discussions, A. Saunders, M. Jösch, and H. Monyer for critically reading earlier versions of the manuscript, C. Petersen for sharing clearing protocols, and the Scientific Service Units of ISTA for efficient support. This project was funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC advanced grant No 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award for P.J. and I3600-B27 for J.G.D. and P.V.)."},{"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","ec_funded":1,"article_processing_charge":"No","scopus_import":"1","publication":"eLife","department":[{"_id":"MaJö"},{"_id":"PeJo"}],"pmid":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"eLife Sciences Publications","article_number":"79848","title":"Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling","file":[{"file_id":"12463","date_updated":"2023-01-30T11:50:53Z","checksum":"5a2a65e3e7225090c3d8199f3bbd7b7b","date_created":"2023-01-30T11:50:53Z","access_level":"open_access","file_name":"2022_eLife_Sumser.pdf","success":1,"file_size":8506811,"relation":"main_file","content_type":"application/pdf","creator":"dernst"}],"day":"15","author":[{"first_name":"Anton L","last_name":"Sumser","id":"3320A096-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4792-1881","full_name":"Sumser, Anton L"},{"id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3937-1330","full_name":"Jösch, Maximilian A","last_name":"Jösch","first_name":"Maximilian A"},{"last_name":"Jonas","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M"},{"id":"43DF3136-F248-11E8-B48F-1D18A9856A87","full_name":"Ben Simon, Yoav","last_name":"Ben Simon","first_name":"Yoav"}],"language":[{"iso":"eng"}],"keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"isi":1,"project":[{"grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse"},{"name":"Circuits of Visual Attention","call_identifier":"H2020","_id":"2634E9D2-B435-11E9-9278-68D0E5697425","grant_number":"756502"},{"name":"The Wittgenstein Prize","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312"},{"grant_number":"LT000256","name":"Neuronal networks of salience and spatial detection in the murine superior colliculus","_id":"266D407A-B435-11E9-9278-68D0E5697425"},{"grant_number":"ALTF 1098-2017","_id":"264FEA02-B435-11E9-9278-68D0E5697425","name":"Connecting sensory with motor processing in the superior colliculus"}],"quality_controlled":"1","doi":"10.7554/elife.79848","publication_identifier":{"eissn":["2050-084X"]},"_id":"12288","year":"2022","acknowledgement":"We thank F Marr for technical assistance, A Murray for RVdG-CVS-N2c viruses and Neuro2A packaging cell-lines and J Watson for reading the manuscript. This research was supported by the Scientific Service Units (SSU) of IST-Austria through resources provided by the Imaging and Optics Facility (IOF) and the Preclinical Facility (PCF). This project was funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC advanced grant No 692692, PJ, ERC starting grant No 756502, MJ), the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award, PJ), the Human Frontier Science Program (LT000256/2018-L, AS) and EMBO (ALTF 1098-2017, AS).","date_created":"2023-01-16T10:04:15Z","file_date_updated":"2023-01-30T11:50:53Z","volume":11,"oa_version":"Published Version","type":"journal_article","month":"09","abstract":[{"lang":"eng","text":"To understand the function of neuronal circuits, it is crucial to disentangle the connectivity patterns within the network. However, most tools currently used to explore connectivity have low throughput, low selectivity, or limited accessibility. Here, we report the development of an improved packaging system for the production of the highly neurotropic RVdGenvA-CVS-N2c rabies viral vectors, yielding titers orders of magnitude higher with no background contamination, at a fraction of the production time, while preserving the efficiency of transsynaptic labeling. Along with the production pipeline, we developed suites of ‘starter’ AAV and bicistronic RVdG-CVS-N2c vectors, enabling retrograde labeling from a wide range of neuronal populations, tailored for diverse experimental requirements. We demonstrate the power and flexibility of the new system by uncovering hidden local and distal inhibitory connections in the mouse hippocampal formation and by imaging the functional properties of a cortical microcircuit across weeks. Our novel production pipeline provides a convenient approach to generate new rabies vectors, while our toolkit flexibly and efficiently expands the current capacity to label, manipulate and image the neuronal activity of interconnected neuronal circuits in vitro and in vivo."}],"date_updated":"2023-08-04T10:29:48Z","citation":{"ieee":"A. L. Sumser, M. A. Jösch, P. M. Jonas, and Y. Ben Simon, “Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","chicago":"Sumser, Anton L, Maximilian A Jösch, Peter M Jonas, and Yoav Ben Simon. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/elife.79848\">https://doi.org/10.7554/elife.79848</a>.","short":"A.L. Sumser, M.A. Jösch, P.M. Jonas, Y. Ben Simon, ELife 11 (2022).","ama":"Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/elife.79848\">10.7554/elife.79848</a>","ista":"Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. 2022. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. eLife. 11, 79848.","mla":"Sumser, Anton L., et al. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” <i>ELife</i>, vol. 11, 79848, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/elife.79848\">10.7554/elife.79848</a>.","apa":"Sumser, A. L., Jösch, M. A., Jonas, P. M., &#38; Ben Simon, Y. (2022). Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.79848\">https://doi.org/10.7554/elife.79848</a>"},"intvolume":"        11","external_id":{"isi":["000892204300001"],"pmid":["36040301"]},"status":"public","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"date_published":"2022-09-15T00:00:00Z","ddc":["570"],"has_accepted_license":"1","oa":1,"publication_status":"published"}]