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Danzl, (2023).","ieee":"J. G. Danzl, “Research data for the publication ‘Imaging brain tissue architecture across millimeter to nanometer scales.’” Institute of Science and Technology Austria, 2023.","ama":"Danzl JG. Research data for the publication “Imaging brain tissue architecture across millimeter to nanometer scales.” 2023. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:13126\">10.15479/AT:ISTA:13126</a>","mla":"Danzl, Johann G. <i>Research Data for the Publication “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.”</i> Institute of Science and Technology Austria, 2023, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:13126\">10.15479/AT:ISTA:13126</a>.","apa":"Danzl, J. G. (2023). Research data for the publication “Imaging brain tissue architecture across millimeter to nanometer scales.” Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:13126\">https://doi.org/10.15479/AT:ISTA:13126</a>","ista":"Danzl JG. 2023. Research data for the publication ‘Imaging brain tissue architecture across millimeter to nanometer scales’, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:13126\">10.15479/AT:ISTA:13126</a>.","chicago":"Danzl, Johann G. “Research Data for the Publication ‘Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.’” Institute of Science and Technology Austria, 2023. <a href=\"https://doi.org/10.15479/AT:ISTA:13126\">https://doi.org/10.15479/AT:ISTA:13126</a>."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa":1,"date_created":"2023-06-07T07:15:12Z","author":[{"orcid":"0000-0001-8559-3973","first_name":"Johann G","last_name":"Danzl","full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"}],"day":"04","oa_version":"Published Version","title":"Research data for the publication \"Imaging brain tissue architecture across millimeter to nanometer scales\"","file_date_updated":"2023-08-04T13:19:47Z","has_accepted_license":"1","abstract":[{"lang":"eng","text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here, we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease."}],"license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","tmp":{"image":"/images/cc_by_nc_sa.png","name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","short":"CC BY-NC-SA (4.0)"},"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}]},{"publication_identifier":{"issn":["1548-7091"],"eissn":["1548-7105"]},"publication_status":"published","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"E-Lib"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"intvolume":"        20","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."}],"date_created":"2023-07-23T22:01:13Z","article_type":"original","volume":20,"title":"Dense 4D nanoscale reconstruction of living brain tissue","oa_version":"Published Version","day":"01","scopus_import":"1","author":[{"first_name":"Philipp","orcid":"0000-0002-2340-7431","last_name":"Velicky","full_name":"Velicky, Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-5665-0430","first_name":"Eder","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","full_name":"Miguel Villalba, Eder","last_name":"Miguel Villalba"},{"last_name":"Michalska","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","full_name":"Michalska, Julia M","first_name":"Julia M","orcid":"0000-0003-3862-1235"},{"first_name":"Julia","last_name":"Lyudchik","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia"},{"last_name":"Wei","full_name":"Wei, Donglai","first_name":"Donglai"},{"last_name":"Lin","full_name":"Lin, Zudi","first_name":"Zudi"},{"first_name":"Jake","orcid":"0000-0002-8698-3823","last_name":"Watson","id":"63836096-4690-11EA-BD4E-32803DDC885E","full_name":"Watson, Jake"},{"first_name":"Jakob","last_name":"Troidl","full_name":"Troidl, Jakob"},{"full_name":"Beyer, Johanna","last_name":"Beyer","first_name":"Johanna"},{"id":"43DF3136-F248-11E8-B48F-1D18A9856A87","full_name":"Ben Simon, Yoav","last_name":"Ben Simon","first_name":"Yoav"},{"first_name":"Christoph M","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer"},{"first_name":"Wiebke","full_name":"Jahr, Wiebke","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","last_name":"Jahr"},{"first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","full_name":"Cenameri, Alban","last_name":"Cenameri"},{"last_name":"Broichhagen","full_name":"Broichhagen, Johannes","first_name":"Johannes"},{"first_name":"Seth G.N.","last_name":"Grant","full_name":"Grant, Seth G.N."},{"orcid":"0000-0001-5001-4804","first_name":"Peter M","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas"},{"first_name":"Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Pfister","full_name":"Pfister, Hanspeter","first_name":"Hanspeter"},{"last_name":"Bickel","full_name":"Bickel, Bernd","id":"49876194-F248-11E8-B48F-1D18A9856A87","first_name":"Bernd","orcid":"0000-0001-6511-9385"},{"full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","orcid":"0000-0001-8559-3973","first_name":"Johann G"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"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>.","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>","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.","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>.","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.","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.","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>"},"language":[{"iso":"eng"}],"oa":1,"department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"},{"_id":"Bio"}],"month":"08","quality_controlled":"1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1038/s41592-023-01936-6"}],"page":"1256-1265","type":"journal_article","_id":"13267","date_updated":"2024-01-10T08:37:48Z","publisher":"Springer Nature","article_processing_charge":"Yes","doi":"10.1038/s41592-023-01936-6","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.).","date_published":"2023-08-01T00:00:00Z","ec_funded":1,"pmid":1,"publication":"Nature Methods","status":"public","project":[{"call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600","_id":"265CB4D0-B435-11E9-9278-68D0E5697425"},{"grant_number":"W1232-B24","name":"Molecular Drug Targets","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"The Wittgenstein Prize","grant_number":"Z00312"},{"name":"High content imaging to decode human immune cell interactions in health and allergic disease","_id":"23889792-32DE-11EA-91FC-C7463DDC885E"},{"call_identifier":"H2020","name":"International IST Doctoral Program","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"},{"_id":"24F9549A-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"715767","name":"MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling"},{"grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"name":"Synaptic computations of the hippocampal CA3 circuitry","grant_number":"101026635","call_identifier":"H2020","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9"},{"_id":"2668BFA0-B435-11E9-9278-68D0E5697425","name":"High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration","grant_number":"LT00057"}],"related_material":{"link":[{"url":"https://github.com/danzllab/LIONESS","relation":"software"}],"record":[{"id":"12817","relation":"research_data","status":"public"},{"status":"public","relation":"shorter_version","id":"14770"}]},"external_id":{"pmid":["37429995"],"isi":["001025621500001"]},"isi":1,"year":"2023"},{"publication_identifier":{"eissn":["1546-1696"],"issn":["1087-0156"]},"publication_status":"epub_ahead","abstract":[{"text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease.","lang":"eng"}],"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"article_type":"original","date_created":"2023-09-03T22:01:15Z","author":[{"first_name":"Julia M","orcid":"0000-0003-3862-1235","full_name":"Michalska, Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","last_name":"Michalska"},{"last_name":"Lyudchik","full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia"},{"orcid":"0000-0002-2340-7431","first_name":"Philipp","last_name":"Velicky","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","full_name":"Velicky, Philipp"},{"last_name":"Korinkova","full_name":"Korinkova, Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","first_name":"Hana"},{"last_name":"Watson","id":"63836096-4690-11EA-BD4E-32803DDC885E","full_name":"Watson, Jake","orcid":"0000-0002-8698-3823","first_name":"Jake"},{"first_name":"Alban","last_name":"Cenameri","id":"9ac8f577-2357-11eb-997a-e566c5550886","full_name":"Cenameri, Alban"},{"last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","first_name":"Christoph M","orcid":"0000-0003-1216-9105"},{"full_name":"Amberg, Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","last_name":"Amberg","orcid":"0000-0002-3183-8207","first_name":"Nicole"},{"first_name":"Alessandro","orcid":"0000-0003-2356-9403","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","full_name":"Venturino, Alessandro","last_name":"Venturino"},{"first_name":"Karl","full_name":"Roessler, Karl","last_name":"Roessler"},{"first_name":"Thomas","full_name":"Czech, Thomas","last_name":"Czech"},{"last_name":"Höftberger","full_name":"Höftberger, Romana","first_name":"Romana"},{"last_name":"Siegert","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877","first_name":"Sandra"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","last_name":"Novarino","orcid":"0000-0002-7673-7178","first_name":"Gaia"},{"last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","first_name":"Peter M","orcid":"0000-0001-5001-4804"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","last_name":"Danzl","first_name":"Johann G","orcid":"0000-0001-8559-3973"}],"scopus_import":"1","day":"31","title":"Imaging brain tissue architecture across millimeter to nanometer scales","oa_version":"Published Version","citation":{"ama":"Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture across millimeter to nanometer scales. <i>Nature Biotechnology</i>. 2023. doi:<a href=\"https://doi.org/10.1038/s41587-023-01911-8\">10.1038/s41587-023-01911-8</a>","ieee":"J. M. Michalska <i>et al.</i>, “Imaging brain tissue architecture across millimeter to nanometer scales,” <i>Nature Biotechnology</i>. Springer Nature, 2023.","short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology (2023).","ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino G, Jonas PM, Danzl JG. 2023. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology.","chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” <i>Nature Biotechnology</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41587-023-01911-8\">https://doi.org/10.1038/s41587-023-01911-8</a>.","apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (2023). Imaging brain tissue architecture across millimeter to nanometer scales. <i>Nature Biotechnology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41587-023-01911-8\">https://doi.org/10.1038/s41587-023-01911-8</a>","mla":"Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” <i>Nature Biotechnology</i>, Springer Nature, 2023, doi:<a href=\"https://doi.org/10.1038/s41587-023-01911-8\">10.1038/s41587-023-01911-8</a>."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa":1,"language":[{"iso":"eng"}],"department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"},{"_id":"Bio"},{"_id":"RySh"}],"month":"08","main_file_link":[{"url":"https://doi.org/10.1038/s41587-023-01911-8","open_access":"1"}],"quality_controlled":"1","date_updated":"2024-02-21T12:18:18Z","_id":"14257","type":"journal_article","doi":"10.1038/s41587-023-01911-8","article_processing_charge":"Yes (in subscription journal)","publisher":"Springer Nature","ec_funded":1,"acknowledgement":"We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I. Erber for technical assistance; and M. Tomschik for support with obtaining human samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata for computational support and hardware control. We are grateful to R. Shigemoto and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University) for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly provided by S. Grant (University of Edinburgh). We acknowledge expert support by Institute of Science and Technology Austria’s scientific computing, imaging and optics, preclinical and lab support facilities and by the Miba machine shop and library. We gratefully acknowledge funding by the following sources: Austrian Science Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232 (J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award (P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27 (R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 692692 – GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).","date_published":"2023-08-31T00:00:00Z","project":[{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600","call_identifier":"FWF"},{"call_identifier":"FWF","grant_number":"W1232-B24","name":"Molecular Drug Targets","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","grant_number":"Z00312","name":"The Wittgenstein Prize","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"name":"High content imaging to decode human immune cell interactions in health and allergic disease","_id":"23889792-32DE-11EA-91FC-C7463DDC885E"},{"call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program","grant_number":"665385","call_identifier":"H2020"},{"_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","name":"Synaptic computations of the hippocampal CA3 circuitry","grant_number":"101026635","call_identifier":"H2020"}],"status":"public","publication":"Nature Biotechnology","year":"2023","isi":1,"external_id":{"isi":["001065254200001"]},"related_material":{"link":[{"relation":"software","url":"https://github.com/danzllab/CATS"}],"record":[{"status":"public","relation":"research_data","id":"13126"}]}},{"oa":1,"language":[{"iso":"eng"}],"citation":{"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>.","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>","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>.","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>","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.","short":"Y. Ben Simon, K. Käfer, P. Velicky, J.L. Csicsvari, J.G. Danzl, P.M. Jonas, Nature Communications 13 (2022)."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","month":"08","department":[{"_id":"JoCs"},{"_id":"PeJo"},{"_id":"JoDa"}],"article_number":"4826","file":[{"date_created":"2022-08-26T11:51:40Z","file_size":5910357,"creator":"dernst","date_updated":"2022-08-26T11:51:40Z","file_id":"11990","file_name":"2022_NatureCommunications_BenSimon.pdf","success":1,"content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"405936d9e4d33625d80c093c9713a91f"}],"has_accepted_license":"1","acknowledged_ssus":[{"_id":"Bio"},{"_id":"SSU"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"license":"https://creativecommons.org/licenses/by/4.0/","intvolume":"        13","abstract":[{"lang":"eng","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."}],"file_date_updated":"2022-08-26T11:51:40Z","publication_status":"published","publication_identifier":{"issn":["2041-1723"]},"day":"16","author":[{"full_name":"Ben Simon, Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","last_name":"Ben Simon","first_name":"Yoav"},{"last_name":"Käfer","id":"2DAA49AA-F248-11E8-B48F-1D18A9856A87","full_name":"Käfer, Karola","first_name":"Karola"},{"orcid":"0000-0002-2340-7431","first_name":"Philipp","full_name":"Velicky, Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","last_name":"Velicky"},{"id":"3FA14672-F248-11E8-B48F-1D18A9856A87","full_name":"Csicsvari, Jozsef L","last_name":"Csicsvari","first_name":"Jozsef L","orcid":"0000-0002-5193-4036"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","last_name":"Danzl","first_name":"Johann G","orcid":"0000-0001-8559-3973"},{"first_name":"Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"title":"A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory","oa_version":"Published Version","volume":13,"date_created":"2022-08-24T08:25:50Z","article_type":"original","status":"public","publication":"Nature Communications","project":[{"name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425"},{"grant_number":"Z00312","name":"The Wittgenstein Prize","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425"}],"ec_funded":1,"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.).","date_published":"2022-08-16T00:00:00Z","year":"2022","isi":1,"external_id":{"isi":["000841396400008"]},"keyword":["General Physics and Astronomy","General Biochemistry","Genetics and Molecular Biology","General Chemistry","Multidisciplinary"],"ddc":["570"],"quality_controlled":"1","article_processing_charge":"No","doi":"10.1038/s41467-022-32559-8","publisher":"Springer Nature","_id":"11951","date_updated":"2023-08-03T13:01:19Z","type":"journal_article"},{"day":"24","author":[{"first_name":"Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","full_name":"Morandell, Jasmin","last_name":"Morandell"},{"last_name":"Schwarz","full_name":"Schwarz, Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","first_name":"Lena A"},{"first_name":"Bernadette","orcid":"0000-0003-1843-3173","full_name":"Basilico, Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","last_name":"Basilico"},{"orcid":"0000-0003-1671-393X","first_name":"Saren","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","full_name":"Tasciyan, Saren","last_name":"Tasciyan"},{"last_name":"Dimchev","full_name":"Dimchev, Georgi A","id":"38C393BE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8370-6161","first_name":"Georgi A"},{"first_name":"Armel","last_name":"Nicolas","id":"2A103192-F248-11E8-B48F-1D18A9856A87","full_name":"Nicolas, Armel"},{"orcid":"0000-0003-1216-9105","first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M"},{"last_name":"Kreuzinger","full_name":"Kreuzinger, Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87","first_name":"Caroline"},{"last_name":"Dotter","full_name":"Dotter, Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9033-9096","first_name":"Christoph"},{"last_name":"Knaus","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","full_name":"Knaus, Lisa","first_name":"Lisa"},{"first_name":"Zoe","last_name":"Dobler","full_name":"Dobler, Zoe","id":"D23090A2-9057-11EA-883A-A8396FC7A38F"},{"full_name":"Cacci, Emanuele","last_name":"Cacci","first_name":"Emanuele"},{"id":"48AD8942-F248-11E8-B48F-1D18A9856A87","full_name":"Schur, Florian KM","last_name":"Schur","orcid":"0000-0003-4790-8078","first_name":"Florian KM"},{"orcid":"0000-0001-8559-3973","first_name":"Johann G","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G"},{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178"}],"oa_version":"Published Version","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","volume":12,"date_created":"2021-05-28T11:49:46Z","article_type":"original","has_accepted_license":"1","acknowledged_ssus":[{"_id":"PreCl"}],"intvolume":"        12","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"abstract":[{"lang":"eng","text":"De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency leads to motor coordination deficits as well as ASD-relevant social and cognitive impairments. However, induction of Cul3 haploinsufficiency later in life does not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during a critical developmental window. Here we show that Cul3 is essential to regulate neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice display cortical lamination abnormalities. At the molecular level, we found that Cul3 controls neuronal migration by tightly regulating the amount of Plastin3 (Pls3), a previously unrecognized player of neural migration. Furthermore, we found that Pls3 cell-autonomously regulates cell migration by regulating actin cytoskeleton organization, and its levels are inversely proportional to neural migration speed. Finally, we provide evidence that cellular phenotypes associated with autism-linked gene haploinsufficiency can be rescued by transcriptional activation of the intact allele in vitro, offering a proof of concept for a potential therapeutic approach for ASDs."}],"file_date_updated":"2021-05-28T12:39:43Z","publication_status":"published","publication_identifier":{"eissn":["2041-1723"]},"month":"05","department":[{"_id":"GaNo"},{"_id":"JoDa"},{"_id":"FlSc"},{"_id":"MiSi"},{"_id":"LifeSc"},{"_id":"Bio"}],"article_number":"3058","file":[{"relation":"main_file","checksum":"337e0f7959c35ec959984cacdcb472ba","file_name":"2021_NatureCommunications_Morandell.pdf","success":1,"content_type":"application/pdf","access_level":"open_access","file_id":"9430","file_size":9358599,"date_created":"2021-05-28T12:39:43Z","date_updated":"2021-05-28T12:39:43Z","creator":"kschuh"}],"oa":1,"language":[{"iso":"eng"}],"citation":{"ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>Nature Communications</i>. 2021;12(1). doi:<a href=\"https://doi.org/10.1038/s41467-021-23123-x\">10.1038/s41467-021-23123-x</a>","ieee":"J. Morandell <i>et al.</i>, “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” <i>Nature Communications</i>, vol. 12, no. 1. Springer Nature, 2021.","short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas, C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur, J.G. Danzl, G. Novarino, Nature Communications 12 (2021).","chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>Nature Communications</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41467-021-23123-x\">https://doi.org/10.1038/s41467-021-23123-x</a>.","ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 12(1), 3058.","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A., Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-021-23123-x\">https://doi.org/10.1038/s41467-021-23123-x</a>","mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>Nature Communications</i>, vol. 12, no. 1, 3058, Springer Nature, 2021, doi:<a href=\"https://doi.org/10.1038/s41467-021-23123-x\">10.1038/s41467-021-23123-x</a>."},"issue":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","doi":"10.1038/s41467-021-23123-x","publisher":"Springer Nature","_id":"9429","date_updated":"2024-09-10T12:04:26Z","type":"journal_article","ddc":["572"],"quality_controlled":"1","isi":1,"year":"2021","related_material":{"record":[{"id":"7800","status":"public","relation":"earlier_version"},{"id":"12401","relation":"dissertation_contains","status":"public"}],"link":[{"url":"https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/","relation":"press_release"}]},"external_id":{"isi":["000658769900010"]},"keyword":["General Biochemistry","Genetics and Molecular Biology"],"publication":"Nature Communications","status":"public","project":[{"_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411"},{"_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","grant_number":"715508"},{"call_identifier":"FWF","grant_number":"W1232-B24","name":"Molecular Drug Targets","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"grant_number":"F07807","name":"Neural stem cells in autism and epilepsy","_id":"05A0D778-7A3F-11EA-A408-12923DDC885E"},{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules"}],"ec_funded":1,"acknowledgement":"We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A. Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the management of our animal colony, as well as M. Schunn and the Preclinical Facility team for technical assistance. We thank K. Heesom and her team at the University of Bristol Proteomics Facility for the proteomics sample preparation, data generation, and analysis support. We thank Y. B. Simon for kindly providing the plasmid for lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration and the fruitful discussions. This work was supported by the ISTPlus postdoctoral fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D (I3600-B27).","date_published":"2021-05-24T00:00:00Z"},{"author":[{"first_name":"Jasmin","full_name":"Morandell, Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","last_name":"Morandell"},{"first_name":"Lena A","last_name":"Schwarz","full_name":"Schwarz, Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Bernadette","orcid":"0000-0003-1843-3173","last_name":"Basilico","full_name":"Basilico, Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425"},{"last_name":"Tasciyan","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","full_name":"Tasciyan, Saren","first_name":"Saren","orcid":"0000-0003-1671-393X"},{"first_name":"Armel","full_name":"Nicolas, Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87","last_name":"Nicolas"},{"last_name":"Sommer","full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","first_name":"Christoph M"},{"first_name":"Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87","full_name":"Kreuzinger, Caroline","last_name":"Kreuzinger"},{"last_name":"Knaus","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","full_name":"Knaus, Lisa","first_name":"Lisa"},{"first_name":"Zoe","last_name":"Dobler","id":"D23090A2-9057-11EA-883A-A8396FC7A38F","full_name":"Dobler, Zoe"},{"first_name":"Emanuele","last_name":"Cacci","full_name":"Cacci, Emanuele"},{"orcid":"0000-0001-8559-3973","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","last_name":"Danzl"},{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178"}],"day":"11","oa_version":"Preprint","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","date_created":"2020-05-05T14:31:33Z","has_accepted_license":"1","tmp":{"image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)"},"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","abstract":[{"text":"De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 (CUL3) lead to autism spectrum disorder (ASD). Here, we used Cul3 mouse models to evaluate the consequences of Cul3 mutations in vivo. Our results show that Cul3 haploinsufficient mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments. Cul3 mutant brain displays cortical lamination abnormalities due to defective neuronal migration and reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal columnar organization, Cul3 haploinsufficiency is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level, employing a quantitative proteomic approach, we show that Cul3 regulates cytoskeletal and adhesion protein abundance in mouse embryos. Abnormal regulation of cytoskeletal proteins in Cul3 mutant neuronal cells results in atypical organization of the actin mesh at the cell leading edge, likely causing the observed migration deficits. In contrast to these important functions early in development, Cul3 deficiency appears less relevant at adult stages. In fact, induction of Cul3 haploinsufficiency in adult mice does not result in the behavioral defects observed in constitutive Cul3 haploinsufficient animals. Taken together, our data indicate that Cul3 has a critical role in the regulation of cytoskeletal proteins and neuronal migration and that ASD-associated defects and behavioral abnormalities are primarily due to Cul3 functions at early developmental stages.","lang":"eng"}],"acknowledged_ssus":[{"_id":"PreCl"}],"publication_status":"submitted","file_date_updated":"2020-07-14T12:48:03Z","month":"01","department":[{"_id":"JoDa"},{"_id":"GaNo"},{"_id":"LifeSc"}],"file":[{"checksum":"c6799ab5daba80efe8e2ed63c15f8c81","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"2020.01.10.902064v1.full.pdf","file_id":"7801","date_updated":"2020-07-14T12:48:03Z","creator":"rsix","file_size":2931370,"date_created":"2020-05-05T14:31:19Z"}],"oa":1,"language":[{"iso":"eng"}],"citation":{"ieee":"J. Morandell <i>et al.</i>, “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, A. Nicolas, C.M. Sommer, C. Kreuzinger, L. Knaus, Z. Dobler, E. Cacci, J.G. Danzl, G. Novarino, BioRxiv (n.d.).","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2020.01.10.902064 \">10.1101/2020.01.10.902064 </a>","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Nicolas, A., Sommer, C. M., … Novarino, G. (n.d.). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2020.01.10.902064 \">https://doi.org/10.1101/2020.01.10.902064 </a>","mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2020.01.10.902064 \">10.1101/2020.01.10.902064 </a>.","ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Nicolas A, Sommer CM, Kreuzinger C, Knaus L, Dobler Z, Cacci E, Danzl JG, Novarino G. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv, <a href=\"https://doi.org/10.1101/2020.01.10.902064 \">10.1101/2020.01.10.902064 </a>.","chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Armel Nicolas, Christoph M Sommer, Caroline Kreuzinger, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2020.01.10.902064 \">https://doi.org/10.1101/2020.01.10.902064 </a>."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","doi":"10.1101/2020.01.10.902064 ","article_processing_charge":"No","publisher":"Cold Spring Harbor Laboratory","date_updated":"2024-09-10T12:04:26Z","_id":"7800","type":"preprint","ddc":["570"],"year":"2020","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"8620"},{"id":"9429","status":"public","relation":"later_version"}]},"project":[{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600","call_identifier":"FWF"},{"call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232-B24","_id":"2548AE96-B435-11E9-9278-68D0E5697425"}],"status":"public","publication":"bioRxiv","date_published":"2020-01-11T00:00:00Z"},{"publication_status":"published","publication_identifier":{"issn":["1046-2023"]},"abstract":[{"lang":"eng","text":"Super-resolution fluorescence microscopy has become an important catalyst for discovery in the life sciences. In STimulated Emission Depletion (STED) microscopy, a pattern of light drives fluorophores from a signal-emitting on-state to a non-signalling off-state. Only emitters residing in a sub-diffraction volume around an intensity minimum are allowed to fluoresce, rendering them distinguishable from the nearby, but dark fluorophores. STED routinely achieves resolution in the few tens of nanometers range in biological samples and is suitable for live imaging. Here, we review the working principle of STED and provide general guidelines for successful STED imaging. The strive for ever higher resolution comes at the cost of increased light burden. We discuss techniques to reduce light exposure and mitigate its detrimental effects on the specimen. These include specialized illumination strategies as well as protecting fluorophores from photobleaching mediated by high-intensity STED light. This opens up the prospect of volumetric imaging in living cells and tissues with diffraction-unlimited resolution in all three spatial dimensions."}],"intvolume":"       174","article_type":"original","date_created":"2019-08-12T16:36:32Z","volume":174,"title":"Strategies to maximize performance in STimulated Emission Depletion (STED) nanoscopy of biological specimens","oa_version":"Submitted Version","author":[{"last_name":"Jahr","full_name":"Jahr, Wiebke","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","first_name":"Wiebke"},{"last_name":"Velicky","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","full_name":"Velicky, Philipp","first_name":"Philipp","orcid":"0000-0002-2340-7431"},{"orcid":"0000-0001-8559-3973","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","last_name":"Danzl"}],"scopus_import":"1","day":"01","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","issue":"3","citation":{"ieee":"W. Jahr, P. Velicky, and J. G. Danzl, “Strategies to maximize performance in STimulated Emission Depletion (STED) nanoscopy of biological specimens,” <i>Methods</i>, vol. 174, no. 3. Elsevier, pp. 27–41, 2020.","short":"W. Jahr, P. Velicky, J.G. Danzl, Methods 174 (2020) 27–41.","ama":"Jahr W, Velicky P, Danzl JG. Strategies to maximize performance in STimulated Emission Depletion (STED) nanoscopy of biological specimens. <i>Methods</i>. 2020;174(3):27-41. doi:<a href=\"https://doi.org/10.1016/j.ymeth.2019.07.019\">10.1016/j.ymeth.2019.07.019</a>","apa":"Jahr, W., Velicky, P., &#38; Danzl, J. G. (2020). Strategies to maximize performance in STimulated Emission Depletion (STED) nanoscopy of biological specimens. <i>Methods</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.ymeth.2019.07.019\">https://doi.org/10.1016/j.ymeth.2019.07.019</a>","mla":"Jahr, Wiebke, et al. “Strategies to Maximize Performance in STimulated Emission Depletion (STED) Nanoscopy of Biological Specimens.” <i>Methods</i>, vol. 174, no. 3, Elsevier, 2020, pp. 27–41, doi:<a href=\"https://doi.org/10.1016/j.ymeth.2019.07.019\">10.1016/j.ymeth.2019.07.019</a>.","chicago":"Jahr, Wiebke, Philipp Velicky, and Johann G Danzl. “Strategies to Maximize Performance in STimulated Emission Depletion (STED) Nanoscopy of Biological Specimens.” <i>Methods</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.ymeth.2019.07.019\">https://doi.org/10.1016/j.ymeth.2019.07.019</a>.","ista":"Jahr W, Velicky P, Danzl JG. 2020. Strategies to maximize performance in STimulated Emission Depletion (STED) nanoscopy of biological specimens. Methods. 174(3), 27–41."},"language":[{"iso":"eng"}],"oa":1,"department":[{"_id":"JoDa"}],"month":"03","quality_controlled":"1","main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100895/"}],"page":"27-41","type":"journal_article","date_updated":"2023-08-17T13:59:57Z","_id":"6808","publisher":"Elsevier","doi":"10.1016/j.ymeth.2019.07.019","article_processing_charge":"No","date_published":"2020-03-01T00:00:00Z","pmid":1,"project":[{"call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600","_id":"265CB4D0-B435-11E9-9278-68D0E5697425"},{"name":"High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration","grant_number":"LT00057","_id":"2668BFA0-B435-11E9-9278-68D0E5697425"}],"status":"public","publication":"Methods","external_id":{"isi":["000525860400005"],"pmid":["31344404"]},"isi":1,"year":"2020"},{"external_id":{"isi":["000525582200001"]},"isi":1,"year":"2020","date_published":"2020-03-19T00:00:00Z","ec_funded":1,"publication":"Frontiers in Cellular Neuroscience","status":"public","project":[{"_id":"2659CC84-B435-11E9-9278-68D0E5697425","name":"Ultrastructural analysis of phosphoinositides in nerve terminals: distribution, dynamics and physiological roles in synaptic transmission","grant_number":"793482","call_identifier":"H2020"},{"call_identifier":"H2020","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","grant_number":"694539","_id":"25CA28EA-B435-11E9-9278-68D0E5697425"},{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules"},{"_id":"B67AFEDC-15C9-11EA-A837-991A96BB2854","name":"IST Austria Open Access Fund"}],"type":"journal_article","_id":"7665","date_updated":"2023-08-21T06:12:48Z","publisher":"Frontiers Media","article_processing_charge":"Yes (via OA deal)","doi":"10.3389/fncel.2020.00063","quality_controlled":"1","ddc":["570"],"article_number":"63","file":[{"checksum":"1c145123c6f8dc3e2e4bd5a66a1ad60e","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"2020_FrontiersCellularNeurosc_Eguchi.pdf","file_id":"7668","creator":"dernst","date_updated":"2020-07-14T12:48:01Z","date_created":"2020-04-20T10:59:49Z","file_size":9227283}],"department":[{"_id":"JoDa"},{"_id":"RySh"}],"month":"03","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"ama":"Eguchi K, Velicky P, Saeckl E, et al. Advantages of acute brain slices prepared at physiological temperature in the characterization of synaptic functions. <i>Frontiers in Cellular Neuroscience</i>. 2020;14. doi:<a href=\"https://doi.org/10.3389/fncel.2020.00063\">10.3389/fncel.2020.00063</a>","short":"K. Eguchi, P. Velicky, E. Saeckl, M. Itakura, Y. Fukazawa, J.G. Danzl, R. Shigemoto, Frontiers in Cellular Neuroscience 14 (2020).","ieee":"K. Eguchi <i>et al.</i>, “Advantages of acute brain slices prepared at physiological temperature in the characterization of synaptic functions,” <i>Frontiers in Cellular Neuroscience</i>, vol. 14. Frontiers Media, 2020.","chicago":"Eguchi, Kohgaku, Philipp Velicky, Elena Saeckl, Makoto Itakura, Yugo Fukazawa, Johann G Danzl, and Ryuichi Shigemoto. “Advantages of Acute Brain Slices Prepared at Physiological Temperature in the Characterization of Synaptic Functions.” <i>Frontiers in Cellular Neuroscience</i>. Frontiers Media, 2020. <a href=\"https://doi.org/10.3389/fncel.2020.00063\">https://doi.org/10.3389/fncel.2020.00063</a>.","ista":"Eguchi K, Velicky P, Saeckl E, Itakura M, Fukazawa Y, Danzl JG, Shigemoto R. 2020. Advantages of acute brain slices prepared at physiological temperature in the characterization of synaptic functions. Frontiers in Cellular Neuroscience. 14, 63.","mla":"Eguchi, Kohgaku, et al. “Advantages of Acute Brain Slices Prepared at Physiological Temperature in the Characterization of Synaptic Functions.” <i>Frontiers in Cellular Neuroscience</i>, vol. 14, 63, Frontiers Media, 2020, doi:<a href=\"https://doi.org/10.3389/fncel.2020.00063\">10.3389/fncel.2020.00063</a>.","apa":"Eguchi, K., Velicky, P., Saeckl, E., Itakura, M., Fukazawa, Y., Danzl, J. G., &#38; Shigemoto, R. (2020). Advantages of acute brain slices prepared at physiological temperature in the characterization of synaptic functions. <i>Frontiers in Cellular Neuroscience</i>. Frontiers Media. <a href=\"https://doi.org/10.3389/fncel.2020.00063\">https://doi.org/10.3389/fncel.2020.00063</a>"},"language":[{"iso":"eng"}],"oa":1,"date_created":"2020-04-19T22:00:55Z","article_type":"original","volume":14,"oa_version":"Published Version","title":"Advantages of acute brain slices prepared at physiological temperature in the characterization of synaptic functions","day":"19","scopus_import":"1","author":[{"full_name":"Eguchi, Kohgaku","id":"2B7846DC-F248-11E8-B48F-1D18A9856A87","last_name":"Eguchi","orcid":"0000-0002-6170-2546","first_name":"Kohgaku"},{"last_name":"Velicky","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431","first_name":"Philipp"},{"last_name":"Hollergschwandtner","id":"3C054040-F248-11E8-B48F-1D18A9856A87","full_name":"Hollergschwandtner, Elena","first_name":"Elena"},{"first_name":"Makoto","last_name":"Itakura","full_name":"Itakura, Makoto"},{"first_name":"Yugo","full_name":"Fukazawa, Yugo","last_name":"Fukazawa"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","last_name":"Danzl","first_name":"Johann G","orcid":"0000-0001-8559-3973"},{"first_name":"Ryuichi","orcid":"0000-0001-8761-9444","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi"}],"file_date_updated":"2020-07-14T12:48:01Z","publication_status":"published","publication_identifier":{"issn":["16625102"]},"intvolume":"        14","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"abstract":[{"text":"Acute brain slice preparation is a powerful experimental model for investigating the characteristics of synaptic function in the brain. Although brain tissue is usually cut at ice-cold temperature (CT) to facilitate slicing and avoid neuronal damage, exposure to CT causes molecular and architectural changes of synapses. To address these issues, we investigated ultrastructural and electrophysiological features of synapses in mouse acute cerebellar slices prepared at ice-cold and physiological temperature (PT). In the slices prepared at CT, we found significant spine loss and reconstruction, synaptic vesicle rearrangement and decrease in synaptic proteins, all of which were not detected in slices prepared at PT. Consistent with these structural findings, slices prepared at PT showed higher release probability. Furthermore, preparation at PT allows electrophysiological recording immediately after slicing resulting in higher detectability of long-term depression (LTD) after motor learning compared with that at CT. These results indicate substantial advantages of the slice preparation at PT for investigating synaptic functions in different physiological conditions.","lang":"eng"}],"has_accepted_license":"1"},{"citation":{"short":"S.M. Truckenbrodt, C.M. Sommer, S.O. Rizzoli, J.G. Danzl, Nature Protocols 14 (2019) 832–863.","ieee":"S. M. Truckenbrodt, C. M. Sommer, S. O. Rizzoli, and J. G. Danzl, “A practical guide to optimization in X10 expansion microscopy,” <i>Nature Protocols</i>, vol. 14, no. 3. Nature Publishing Group, pp. 832–863, 2019.","ama":"Truckenbrodt SM, Sommer CM, Rizzoli SO, Danzl JG. A practical guide to optimization in X10 expansion microscopy. <i>Nature Protocols</i>. 2019;14(3):832–863. doi:<a href=\"https://doi.org/10.1038/s41596-018-0117-3\">10.1038/s41596-018-0117-3</a>","mla":"Truckenbrodt, Sven M., et al. “A Practical Guide to Optimization in X10 Expansion Microscopy.” <i>Nature Protocols</i>, vol. 14, no. 3, Nature Publishing Group, 2019, pp. 832–863, doi:<a href=\"https://doi.org/10.1038/s41596-018-0117-3\">10.1038/s41596-018-0117-3</a>.","apa":"Truckenbrodt, S. M., Sommer, C. M., Rizzoli, S. O., &#38; Danzl, J. G. (2019). A practical guide to optimization in X10 expansion microscopy. <i>Nature Protocols</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/s41596-018-0117-3\">https://doi.org/10.1038/s41596-018-0117-3</a>","chicago":"Truckenbrodt, Sven M, Christoph M Sommer, Silvio O Rizzoli, and Johann G Danzl. “A Practical Guide to Optimization in X10 Expansion Microscopy.” <i>Nature Protocols</i>. Nature Publishing Group, 2019. <a href=\"https://doi.org/10.1038/s41596-018-0117-3\">https://doi.org/10.1038/s41596-018-0117-3</a>.","ista":"Truckenbrodt SM, Sommer CM, Rizzoli SO, Danzl JG. 2019. A practical guide to optimization in X10 expansion microscopy. Nature Protocols. 14(3), 832–863."},"issue":"3","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa":1,"language":[{"iso":"eng"}],"department":[{"_id":"JoDa"},{"_id":"Bio"}],"file":[{"file_name":"181031_Truckenbrodt_ExM_NatProtoc.docx","success":1,"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","access_level":"open_access","relation":"main_file","checksum":"7efb9951e7ddf3e3dcc2fb92b859c623","file_size":84478958,"date_created":"2021-06-29T14:41:46Z","creator":"kschuh","date_updated":"2021-06-29T14:41:46Z","file_id":"9619"}],"month":"03","file_date_updated":"2021-06-29T14:41:46Z","publication_status":"published","has_accepted_license":"1","intvolume":"        14","abstract":[{"lang":"eng","text":"Expansion microscopy is a relatively new approach to super-resolution imaging that uses expandable hydrogels to isotropically increase the physical distance between fluorophores in biological samples such as cell cultures or tissue slices. The classic gel recipe results in an expansion factor of ~4×, with a resolution of 60–80 nm. We have recently developed X10 microscopy, which uses a gel that achieves an expansion factor of ~10×, with a resolution of ~25 nm. Here, we provide a step-by-step protocol for X10 expansion microscopy. A typical experiment consists of seven sequential stages: (i) immunostaining, (ii) anchoring, (iii) polymerization, (iv) homogenization, (v) expansion, (vi) imaging, and (vii) validation. The protocol presented here includes recommendations for optimization, pitfalls and their solutions, and detailed guidelines that should increase reproducibility. Although our protocol focuses on X10 expansion microscopy, we detail which of these suggestions are also applicable to classic fourfold expansion microscopy. We exemplify our protocol using primary hippocampal neurons from rats, but our approach can be used with other primary cells or cultured cell lines of interest. This protocol will enable any researcher with basic experience in immunostainings and access to an epifluorescence microscope to perform super-resolution microscopy with X10. The procedure takes 3 d and requires ~5 h of actively handling the sample for labeling and expansion, and another ~3 h for imaging and analysis."}],"volume":14,"date_created":"2019-02-24T22:59:20Z","article_type":"original","scopus_import":"1","day":"01","author":[{"first_name":"Sven M","full_name":"Truckenbrodt, Sven M","id":"45812BD4-F248-11E8-B48F-1D18A9856A87","last_name":"Truckenbrodt"},{"last_name":"Sommer","full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","first_name":"Christoph M"},{"full_name":"Rizzoli, Silvio O","last_name":"Rizzoli","first_name":"Silvio O"},{"full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","first_name":"Johann G","orcid":"0000-0001-8559-3973"}],"oa_version":"Submitted Version","title":"A practical guide to optimization in X10 expansion microscopy","ec_funded":1,"pmid":1,"date_published":"2019-03-01T00:00:00Z","status":"public","publication":"Nature Protocols","project":[{"_id":"260C2330-B435-11E9-9278-68D0E5697425","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","call_identifier":"H2020"},{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF"}],"year":"2019","isi":1,"external_id":{"pmid":["30778205"],"isi":["000459890700008"]},"quality_controlled":"1","page":"832–863","ddc":["570"],"_id":"6052","date_updated":"2023-08-24T14:48:33Z","type":"journal_article","article_processing_charge":"No","doi":"10.1038/s41596-018-0117-3","publisher":"Nature Publishing Group"}]