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information-processing capability of the brain’s cellular network depends on the physical wiring pattern between neurons and their molecular and functional characteristics. Mapping neurons and resolving their individual synaptic connections can be achieved by volumetric imaging at nanoscale resolution with dense cellular labelling. Light microscopy is uniquely positioned to visualize specific molecules but dense, synapse-level circuit reconstruction by light microscopy has been out of reach due to limitations in resolution, contrast, and volumetric imaging capability. Here we developed light-microscopy based connectomics (LICONN). We integrated specifically engineered hydrogel embedding and expansion with comprehensive deep-learning based segmentation and analysis of connectivity, thus directly incorporating molecular information in synapse-level brain tissue reconstructions. LICONN will allow synapse-level brain tissue phenotyping in biological experiments in a readily adoptable manner."}],"contributor":[{"orcid":"0000-0002-7667-6854","contributor_type":"researcher","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","last_name":"Tavakoli","first_name":"Mojtaba"},{"last_name":"Lyudchik","first_name":"Julia","contributor_type":"researcher","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"contributor_type":"researcher","last_name":"Januszewski","first_name":"Michal"},{"first_name":"Vitali","last_name":"Vistunou","id":"7e146587-8972-11ed-ae7b-d7a32ea86a81","contributor_type":"researcher"},{"contributor_type":"researcher","id":"40E7F008-F248-11E8-B48F-1D18A9856A87","last_name":"Agudelo Duenas","first_name":"Nathalie"},{"last_name":"Vorlaufer","first_name":"Jakob","contributor_type":"researcher","id":"937696FA-C996-11E9-8C7C-CF13E6697425"},{"contributor_type":"researcher","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer","first_name":"Christoph M"},{"last_name":"Kreuzinger","first_name":"Caroline","contributor_type":"researcher","id":"382077BA-F248-11E8-B48F-1D18A9856A87"},{"id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","contributor_type":"researcher","first_name":"Bárbara","last_name":"Oliveira"},{"first_name":"Alban","last_name":"Cenameri","contributor_type":"researcher"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","contributor_type":"researcher","first_name":"Gaia","last_name":"Novarino"},{"contributor_type":"researcher","first_name":"Viren","last_name":"Jain"},{"first_name":"Johann G","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","contributor_type":"researcher"}],"related_material":{"record":[{"relation":"used_in_publication","id":"19704","status":"public"}],"link":[{"url":"https://pub.ista.ac.at/group_danzl/data/LICONN/","relation":"research_data","description":"Original datasets of large size (>10GB) and datasets in zarr/n5/ims/npz format are provided via this external link."}]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"ScienComp"},{"_id":"PreCl"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"citation":{"ieee":"J. G. Danzl, J. Lyudchik, and C. Kreuzinger, “Light-microscopy based connectomic reconstruction of mammalian brain tissue.” Institute of Science and Technology Austria, 2025.","mla":"Danzl, Johann G., et al. <i>Light-Microscopy Based Connectomic Reconstruction of Mammalian Brain Tissue</i>. Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:18697\">10.15479/AT:ISTA:18697</a>.","short":"J.G. Danzl, J. Lyudchik, C. Kreuzinger, (2025).","chicago":"Danzl, Johann G, Julia Lyudchik, and Caroline Kreuzinger. “Light-Microscopy Based Connectomic Reconstruction of Mammalian Brain Tissue.” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT:ISTA:18697\">https://doi.org/10.15479/AT:ISTA:18697</a>.","ista":"Danzl JG, Lyudchik J, Kreuzinger C. 2025. Light-microscopy based connectomic reconstruction of mammalian brain tissue, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:18697\">10.15479/AT:ISTA:18697</a>.","ama":"Danzl JG, Lyudchik J, Kreuzinger C. Light-microscopy based connectomic reconstruction of mammalian brain tissue. 2025. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:18697\">10.15479/AT:ISTA:18697</a>","apa":"Danzl, J. G., Lyudchik, J., &#38; Kreuzinger, C. (2025). Light-microscopy based connectomic reconstruction of mammalian brain tissue. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:18697\">https://doi.org/10.15479/AT:ISTA:18697</a>"},"date_updated":"2026-04-28T13:33:34Z","_id":"18697"},{"month":"06","intvolume":"       642","publication_identifier":{"issn":["0028-0836"],"eissn":["1476-4687"]},"publisher":"Springer Nature","publication":"Nature","OA_place":"publisher","has_accepted_license":"1","status":"public","corr_author":"1","article_processing_charge":"Yes (via OA deal)","title":"Light-microscopy-based connectomic reconstruction of mammalian brain tissue","year":"2025","page":"398-410","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","oa_version":"Published Version","date_published":"2025-06-12T00:00:00Z","pmid":1,"volume":642,"ddc":["570"],"external_id":{"pmid":["40335689"],"isi":["001483477000001"]},"acknowledgement":"We thank S. Dorkenwald and P. Li for critical reading of the manuscript, S. Loomba for discussions and E. Miguel for support with data handling. We acknowledge support from ISTA’s scientific service units: Imaging and Optics, Lab Support, Scientific Computing, the preclinical facility, the Miba Machine Shop and the library. We acknowledge funding from the following sources: Austrian Science Fund (FWF) grant DK W1232 (J.G.D. and M.R.T.); Austrian Academy of Sciences DOC fellowship 26137 (M.R.T.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.); the European Union’s Horizon 2020 research and innovation programme and Marie Skłodowska-Curie Actions Fellowship 665385 (J.L.); and the European Union’s Horizon 2020 research and innovation programme and European Research Council (ERC) grant 101044865 ‘SecretAutism’ (G.N.).Open access funding provided by Institute of Science and Technology (IST Austria).","author":[{"orcid":"0000-0002-7667-6854","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","last_name":"Tavakoli","first_name":"Mojtaba","full_name":"Tavakoli, Mojtaba"},{"last_name":"Lyudchik","first_name":"Julia","full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Januszewski, Michał","first_name":"Michał","last_name":"Januszewski"},{"id":"7e146587-8972-11ed-ae7b-d7a32ea86a81","last_name":"Vistunou","full_name":"Vistunou, Vitali","first_name":"Vitali"},{"id":"40E7F008-F248-11E8-B48F-1D18A9856A87","full_name":"Agudelo Duenas, Nathalie","first_name":"Nathalie","last_name":"Agudelo Duenas"},{"last_name":"Vorlaufer","first_name":"Jakob","full_name":"Vorlaufer, Jakob","orcid":"0009-0000-7590-3501","id":"937696FA-C996-11E9-8C7C-CF13E6697425"},{"last_name":"Sommer","full_name":"Sommer, Christoph M","first_name":"Christoph M","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"id":"382077BA-F248-11E8-B48F-1D18A9856A87","first_name":"Caroline","full_name":"Kreuzinger, Caroline","last_name":"Kreuzinger"},{"full_name":"Oliveira, Bárbara","first_name":"Bárbara","last_name":"Oliveira","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban","full_name":"Cenameri, Alban","last_name":"Cenameri"},{"last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Viren","full_name":"Jain, Viren","last_name":"Jain"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","first_name":"Johann G","last_name":"Danzl"}],"_id":"19704","related_material":{"link":[{"relation":"press_release","description":"News on ISTA website","url":"https://ista.ac.at/en/news/piecing-together-the-brain-puzzle/"}],"record":[{"id":"18677","relation":"earlier_version","status":"public"},{"status":"public","relation":"research_data","id":"18697"}]},"date_updated":"2026-04-28T13:33:34Z","quality_controlled":"1","citation":{"ista":"Tavakoli M, Lyudchik J, Januszewski M, Vistunou V, Agudelo Duenas N, Vorlaufer J, Sommer CM, Kreuzinger C, Oliveira B, Cenameri A, Novarino G, Jain V, Danzl JG. 2025. Light-microscopy-based connectomic reconstruction of mammalian brain tissue. Nature. 642, 398–410.","apa":"Tavakoli, M., Lyudchik, J., Januszewski, M., Vistunou, V., Agudelo Duenas, N., Vorlaufer, J., … Danzl, J. G. (2025). Light-microscopy-based connectomic reconstruction of mammalian brain tissue. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-025-08985-1\">https://doi.org/10.1038/s41586-025-08985-1</a>","ama":"Tavakoli M, Lyudchik J, Januszewski M, et al. Light-microscopy-based connectomic reconstruction of mammalian brain tissue. <i>Nature</i>. 2025;642:398-410. doi:<a href=\"https://doi.org/10.1038/s41586-025-08985-1\">10.1038/s41586-025-08985-1</a>","mla":"Tavakoli, Mojtaba, et al. “Light-Microscopy-Based Connectomic Reconstruction of Mammalian Brain Tissue.” <i>Nature</i>, vol. 642, Springer Nature, 2025, pp. 398–410, doi:<a href=\"https://doi.org/10.1038/s41586-025-08985-1\">10.1038/s41586-025-08985-1</a>.","ieee":"M. Tavakoli <i>et al.</i>, “Light-microscopy-based connectomic reconstruction of mammalian brain tissue,” <i>Nature</i>, vol. 642. Springer Nature, pp. 398–410, 2025.","chicago":"Tavakoli, Mojtaba, Julia Lyudchik, Michał Januszewski, Vitali Vistunou, Nathalie Agudelo Duenas, Jakob Vorlaufer, Christoph M Sommer, et al. “Light-Microscopy-Based Connectomic Reconstruction of Mammalian Brain Tissue.” <i>Nature</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1038/s41586-025-08985-1\">https://doi.org/10.1038/s41586-025-08985-1</a>.","short":"M. Tavakoli, J. Lyudchik, M. Januszewski, V. Vistunou, N. Agudelo Duenas, J. Vorlaufer, C.M. Sommer, C. Kreuzinger, B. Oliveira, A. Cenameri, G. Novarino, V. Jain, J.G. Danzl, Nature 642 (2025) 398–410."},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"ScienComp"},{"_id":"PreCl"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"ec_funded":1,"abstract":[{"lang":"eng","text":"The information-processing capability of the brain’s cellular network depends on the physical wiring pattern between neurons and their molecular and functional characteristics. Mapping neurons and resolving their individual synaptic connections can be achieved by volumetric imaging at nanoscale resolution1,2 with dense cellular labelling. Light microscopy is uniquely positioned to visualize specific molecules, but dense, synapse-level circuit reconstruction by light microscopy has been out of reach, owing to limitations in resolution, contrast and volumetric imaging capability. Here we describe light-microscopy-based connectomics (LICONN). We integrated specifically engineered hydrogel embedding and expansion with comprehensive deep-learning-based segmentation and analysis of connectivity, thereby directly incorporating molecular information into synapse-level reconstructions of brain tissue. LICONN will allow synapse-level phenotyping of brain tissue in biological experiments in a readily adoptable manner."}],"language":[{"iso":"eng"}],"file_date_updated":"2025-07-03T06:55:20Z","oa":1,"OA_type":"hybrid","scopus_import":"1","isi":1,"day":"12","PlanS_conform":"1","project":[{"grant_number":"26137","name":"Studying Organelle Structure and Function at Nanoscale Resolution with Expansion Microscopy","_id":"6285a163-2b32-11ec-9570-8e204ca2dba5"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"665385","name":"International IST Doctoral Program"},{"_id":"34ba8964-11ca-11ed-8bc3-e15864e7e9a6","name":"Toward an understanding of the brain interstitial system and the extracellular proteome in health and autism spectrum disorders","grant_number":"101044865"},{"name":"Molecular Drug Targets","grant_number":"W1232-B24","call_identifier":"FWF","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425"}],"article_type":"original","department":[{"_id":"JoDa"},{"_id":"GradSch"},{"_id":"Bio"},{"_id":"GaNo"}],"doi":"10.1038/s41586-025-08985-1","file":[{"relation":"main_file","file_id":"19959","file_size":133201290,"date_created":"2025-07-03T06:55:20Z","creator":"dernst","content_type":"application/pdf","file_name":"2025_Nature_Tavakoli.pdf","date_updated":"2025-07-03T06:55:20Z","success":1,"access_level":"open_access","checksum":"ebc99d7108e728f46db0a009292675ef"}],"date_created":"2025-05-18T22:02:51Z","publication_status":"published","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"type":"journal_article"},{"corr_author":"1","status":"public","has_accepted_license":"1","OA_place":"publisher","publication":"Biophysical Reports","publisher":"Elsevier","publication_identifier":{"eissn":["2667-0747"]},"intvolume":"         5","month":"06","author":[{"first_name":"Jakob","full_name":"Vorlaufer, Jakob","last_name":"Vorlaufer","id":"937696FA-C996-11E9-8C7C-CF13E6697425","orcid":"0009-0000-7590-3501"},{"first_name":"Nikolai","full_name":"Semenov, Nikolai","last_name":"Semenov","id":"e64d39c7-72ef-11ef-b75a-ee3046860d1b"},{"last_name":"Kreuzinger","full_name":"Kreuzinger, Caroline","first_name":"Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Javoor","first_name":"Manjunath","full_name":"Javoor, Manjunath","orcid":"0000-0003-2311-2112","id":"305ab18b-dc7d-11ea-9b2f-b58195228ea2"},{"first_name":"Bettina","full_name":"Zens, Bettina","last_name":"Zens","id":"45FD126C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9561-1239"},{"id":"40E7F008-F248-11E8-B48F-1D18A9856A87","first_name":"Nathalie","full_name":"Agudelo Duenas, Nathalie","last_name":"Agudelo Duenas"},{"full_name":"Tavakoli, Mojtaba","first_name":"Mojtaba","last_name":"Tavakoli","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7667-6854"},{"first_name":"Marek","full_name":"Suplata, Marek","last_name":"Suplata","id":"EE8452B8-C26A-11E9-B157-E80CE6697425"},{"orcid":"0000-0003-0201-2315","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","last_name":"Jahr","full_name":"Jahr, Wiebke","first_name":"Wiebke"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","full_name":"Lyudchik, Julia","last_name":"Lyudchik"},{"id":"60aaa06c-3de5-11eb-9e53-baa88e955dcb","last_name":"Wartak","full_name":"Wartak, Andreas","first_name":"Andreas"},{"id":"48AD8942-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4790-8078","full_name":"Schur, Florian Km","first_name":"Florian Km","last_name":"Schur"},{"orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","full_name":"Danzl, Johann G","first_name":"Johann G"}],"acknowledgement":"We acknowledge expert support by ISTA’s scientific service units, including the Miba Machine Shop, the Electron Microscopy Facility, and the Lab Support Facility. This work has been made possible in part by CZI grant DAF2021-234754 and grant DOI: https://doi.org/10.37921/812628ebpcwg from the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation (funder DOI: https://doi.org/10.13039/100014989) (F.K.M.S. and J.G.D.). We further gratefully acknowledge funding by the following sources: Austrian Science Fund (FWF) grant DK W1232 (M.R.T. and J.G.D.); Austrian Academy of Sciences DOC fellowship 26137 (M.R.T.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (J.L.); ISTA postdoctoral fellowship IST fellow (A.W.); and Human Frontier Science Program postdoctoral fellowship LT000557/2018 (W.J.).","article_number":"100211","ddc":["570"],"oa_version":"Published Version","date_published":"2025-06-11T00:00:00Z","volume":5,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2025","title":"Image-based 3D active sample stabilization on the nanometer scale for optical microscopy","article_processing_charge":"Yes","scopus_import":"1","OA_type":"gold","language":[{"iso":"eng"}],"oa":1,"file_date_updated":"2025-06-10T07:24:46Z","abstract":[{"text":"Super-resolution microscopy often entails long acquisition times of minutes to hours. Since drifts during the acquisition adversely affect data quality, active sample stabilization is commonly used for some of these techniques to reach their full potential. Although drifts in the lateral plane can often be corrected after acquisition, this is not always possible or may come with drawbacks. Therefore, it is appealing to stabilize sample position in three dimensions (3D) during acquisition. Various schemes for active sample stabilization have been demonstrated previously, with some reaching sub-nanometer stability in 3D. Here, we present a scheme for active drift correction that delivers the nanometer-scale 3D stability demanded by state-of-the-art super-resolution techniques and is straightforward to implement compared to previous schemes capable of reaching this level of stabilization precision. Using a refined algorithm that can handle various types of reference structure, without sparse signal peaks being mandatory, we stabilized sample position to ∼1 nm in 3D using objective lenses both with high and low numerical aperture. Our implementation requires only the addition of a simple widefield imaging path and we provide an open-source control software with graphical user interface to facilitate easy adoption of the module. Finally, we demonstrate how this has the potential to enhance data collection for diffraction-limited and super-resolution imaging techniques using single-molecule localization microscopy and cryo-confocal imaging as showcases.","lang":"eng"}],"ec_funded":1,"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"EM-Fac"},{"_id":"LifeSc"}],"DOAJ_listed":"1","date_updated":"2026-04-07T11:48:07Z","citation":{"chicago":"Vorlaufer, Jakob, Nikolai Semenov, Caroline Kreuzinger, Manjunath Javoor, Bettina Zens, Nathalie Agudelo Duenas, Mojtaba Tavakoli, et al. “Image-Based 3D Active Sample Stabilization on the Nanometer Scale for Optical Microscopy.” <i>Biophysical Reports</i>. Elsevier, 2025. <a href=\"https://doi.org/10.1016/j.bpr.2025.100211\">https://doi.org/10.1016/j.bpr.2025.100211</a>.","short":"J. Vorlaufer, N. Semenov, C. Kreuzinger, M. Javoor, B. Zens, N. Agudelo Duenas, M. Tavakoli, M. Suplata, W. Jahr, J. Lyudchik, A. Wartak, F.K. Schur, J.G. Danzl, Biophysical Reports 5 (2025).","mla":"Vorlaufer, Jakob, et al. “Image-Based 3D Active Sample Stabilization on the Nanometer Scale for Optical Microscopy.” <i>Biophysical Reports</i>, vol. 5, no. 2, 100211, Elsevier, 2025, doi:<a href=\"https://doi.org/10.1016/j.bpr.2025.100211\">10.1016/j.bpr.2025.100211</a>.","ieee":"J. Vorlaufer <i>et al.</i>, “Image-based 3D active sample stabilization on the nanometer scale for optical microscopy,” <i>Biophysical Reports</i>, vol. 5, no. 2. Elsevier, 2025.","apa":"Vorlaufer, J., Semenov, N., Kreuzinger, C., Javoor, M., Zens, B., Agudelo Duenas, N., … Danzl, J. G. (2025). Image-based 3D active sample stabilization on the nanometer scale for optical microscopy. <i>Biophysical Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.bpr.2025.100211\">https://doi.org/10.1016/j.bpr.2025.100211</a>","ama":"Vorlaufer J, Semenov N, Kreuzinger C, et al. Image-based 3D active sample stabilization on the nanometer scale for optical microscopy. <i>Biophysical Reports</i>. 2025;5(2). doi:<a href=\"https://doi.org/10.1016/j.bpr.2025.100211\">10.1016/j.bpr.2025.100211</a>","ista":"Vorlaufer J, Semenov N, Kreuzinger C, Javoor M, Zens B, Agudelo Duenas N, Tavakoli M, Suplata M, Jahr W, Lyudchik J, Wartak A, Schur FK, Danzl JG. 2025. Image-based 3D active sample stabilization on the nanometer scale for optical microscopy. Biophysical Reports. 5(2), 100211."},"quality_controlled":"1","related_material":{"record":[{"status":"public","id":"20206","relation":"dissertation_contains"}]},"_id":"19795","issue":"2","type":"journal_article","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"date_created":"2025-06-08T22:01:22Z","publication_status":"published","file":[{"date_updated":"2025-06-10T07:24:46Z","file_name":"2025_BiophysicalReports_Vorlaufer.pdf","checksum":"4018c833f25a3ad3b57e3577fed70334","access_level":"open_access","success":1,"content_type":"application/pdf","date_created":"2025-06-10T07:24:46Z","file_size":7238179,"creator":"dernst","file_id":"19802","relation":"main_file"}],"doi":"10.1016/j.bpr.2025.100211","department":[{"_id":"JoDa"},{"_id":"GradSch"},{"_id":"FlSc"},{"_id":"EM-Fac"}],"article_type":"original","project":[{"_id":"62909c6f-2b32-11ec-9570-e1476aab5308","grant_number":"CZI01","name":"CryoMinflux-guided in-situ molecular census and structure determination"},{"_id":"6285a163-2b32-11ec-9570-8e204ca2dba5","grant_number":"26137","name":"Studying Organelle Structure and Function at Nanoscale Resolution with Expansion Microscopy"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"665385","name":"International IST Doctoral Program"},{"name":"Molecular Drug Targets","grant_number":"W1232-B24","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"name":"High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration","grant_number":"LT00057","_id":"2668BFA0-B435-11E9-9278-68D0E5697425"}],"day":"11"},{"publication_identifier":{"issn":["1087-0156"],"eissn":["1546-1696"]},"month":"07","intvolume":"        42","has_accepted_license":"1","status":"public","corr_author":"1","publisher":"Springer Nature","publication":"Nature Biotechnology","OA_place":"publisher","page":"1051-1064","year":"2024","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","volume":42,"pmid":1,"date_published":"2024-07-01T00:00:00Z","oa_version":"Published Version","article_processing_charge":"Yes (in subscription journal)","title":"Imaging brain tissue architecture across millimeter to nanometer scales","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.).","author":[{"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","first_name":"Julia","last_name":"Lyudchik","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431","full_name":"Velicky, Philipp","first_name":"Philipp","last_name":"Velicky"},{"id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","last_name":"Korinkova","first_name":"Hana","full_name":"Korinkova, Hana"},{"full_name":"Watson, Jake","first_name":"Jake","last_name":"Watson","id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","full_name":"Cenameri, Alban","first_name":"Alban","last_name":"Cenameri"},{"full_name":"Sommer, Christoph M","first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105"},{"first_name":"Nicole","full_name":"Amberg, Nicole","last_name":"Amberg","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207"},{"last_name":"Venturino","full_name":"Venturino, Alessandro","first_name":"Alessandro","orcid":"0000-0003-2356-9403","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Roessler, Karl","first_name":"Karl","last_name":"Roessler"},{"first_name":"Thomas","full_name":"Czech, Thomas","last_name":"Czech"},{"first_name":"Romana","full_name":"Höftberger, Romana","last_name":"Höftberger"},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra","first_name":"Sandra","last_name":"Siegert"},{"last_name":"Novarino","full_name":"Novarino, Gaia","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Jonas","full_name":"Jonas, Peter M","first_name":"Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Danzl, Johann G","first_name":"Johann G","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973"}],"ddc":["570"],"external_id":{"pmid":["37653226"],"isi":["001065254200001"]},"related_material":{"record":[{"relation":"dissertation_contains","id":"18660","status":"deleted"},{"status":"public","id":"13126","relation":"research_data"},{"id":"18674","relation":"dissertation_contains","status":"public"}],"link":[{"url":"https://github.com/danzllab/CATS","relation":"software"}]},"date_updated":"2026-04-14T08:34:35Z","quality_controlled":"1","citation":{"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, 2024. <a href=\"https://doi.org/10.1038/s41587-023-01911-8\">https://doi.org/10.1038/s41587-023-01911-8</a>.","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 42 (2024) 1051–1064.","mla":"Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” <i>Nature Biotechnology</i>, vol. 42, Springer Nature, 2024, pp. 1051–64, 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>, vol. 42. Springer Nature, pp. 1051–1064, 2024.","apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (2024). 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>","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture across millimeter to nanometer scales. <i>Nature Biotechnology</i>. 2024;42:1051-1064. doi:<a href=\"https://doi.org/10.1038/s41587-023-01911-8\">10.1038/s41587-023-01911-8</a>","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. 2024. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. 42, 1051–1064."},"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"_id":"14257","OA_type":"hybrid","scopus_import":"1","ec_funded":1,"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"}],"file_date_updated":"2025-01-09T07:48:01Z","language":[{"iso":"eng"}],"oa":1,"article_type":"original","isi":1,"day":"01","project":[{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600"},{"grant_number":"W1232","name":"Molecular Drug Targets","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312","name":"Synaptic communication in neuronal microcircuits"},{"_id":"23889792-32DE-11EA-91FC-C7463DDC885E","grant_number":"LS18-022","name":"High content imaging to decode human immune cell interactions in health and allergic disease"},{"call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508"},{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"name":"International IST Doctoral Program","grant_number":"665385","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"},{"_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","call_identifier":"H2020","name":"Synaptic computations of the hippocampal CA3 circuitry","grant_number":"101026635"}],"publication_status":"published","date_created":"2023-09-03T22:01:15Z","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"type":"journal_article","doi":"10.1038/s41587-023-01911-8","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"},{"_id":"Bio"},{"_id":"RySh"}],"file":[{"file_size":26065165,"date_created":"2025-01-09T07:48:01Z","creator":"dernst","relation":"main_file","file_id":"18784","file_name":"2024_NatureBiotech_Michalska.pdf","date_updated":"2025-01-09T07:48:01Z","success":1,"access_level":"open_access","checksum":"57d5fafb16f02dcb9f7dddb1bd7e2a71","content_type":"application/pdf"}]},{"oa_version":"Published Version","date_published":"2024-12-18T00:00:00Z","year":"2024","page":"217","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","title":"Image analysis for brain tissue reconstruction with super-resolution light microscopy","article_processing_charge":"No","author":[{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia","first_name":"Julia","last_name":"Lyudchik"}],"ddc":["004"],"publication_identifier":{"isbn":[" 978-3-99078-051-0"],"issn":["2663-337X"]},"month":"12","corr_author":"1","has_accepted_license":"1","status":"public","OA_place":"publisher","publisher":"Institute of Science and Technology Austria","project":[{"call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","name":"International IST Doctoral Program"}],"day":"18","publication_status":"published","supervisor":[{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","first_name":"Johann G","full_name":"Danzl, Johann G","last_name":"Danzl"}],"date_created":"2024-12-18T14:24:43Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)"},"type":"dissertation","degree_awarded":"PhD","doi":"10.15479/at:ista:18674","department":[{"_id":"GradSch"},{"_id":"JoDa"}],"file":[{"content_type":"application/pdf","checksum":"1b42b8073e2bc09fc504da52372248c1","success":1,"access_level":"open_access","date_updated":"2024-12-18T14:17:34Z","file_name":"18122024_PhDthesis_corrected_final_pdfa.pdf","file_id":"18675","relation":"main_file","creator":"jlyudchi","date_created":"2024-12-18T14:17:34Z","file_size":160536833},{"date_updated":"2024-12-18T14:41:53Z","file_name":"18122024_PhDthesis_corrected_final_JL_markup.docx","checksum":"b4da84624060745519723698f7ddf54b","access_level":"closed","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","date_created":"2024-12-18T14:21:06Z","file_size":99172203,"creator":"jlyudchi","file_id":"18676","relation":"source_file"}],"date_updated":"2026-04-14T08:34:35Z","citation":{"ista":"Lyudchik J. 2024. Image analysis for brain tissue reconstruction with super-resolution light microscopy. Institute of Science and Technology Austria.","ama":"Lyudchik J. Image analysis for brain tissue reconstruction with super-resolution light microscopy. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:18674\">10.15479/at:ista:18674</a>","apa":"Lyudchik, J. (2024). <i>Image analysis for brain tissue reconstruction with super-resolution light microscopy</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:18674\">https://doi.org/10.15479/at:ista:18674</a>","ieee":"J. Lyudchik, “Image analysis for brain tissue reconstruction with super-resolution light microscopy,” Institute of Science and Technology Austria, 2024.","mla":"Lyudchik, Julia. <i>Image Analysis for Brain Tissue Reconstruction with Super-Resolution Light Microscopy</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:18674\">10.15479/at:ista:18674</a>.","short":"J. Lyudchik, Image Analysis for Brain Tissue Reconstruction with Super-Resolution Light Microscopy, Institute of Science and Technology Austria, 2024.","chicago":"Lyudchik, Julia. “Image Analysis for Brain Tissue Reconstruction with Super-Resolution Light Microscopy.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:18674\">https://doi.org/10.15479/at:ista:18674</a>."},"acknowledged_ssus":[{"_id":"Bio"}],"related_material":{"record":[{"id":"11160","relation":"part_of_dissertation","status":"public"},{"status":"public","relation":"part_of_dissertation","id":"18677"},{"status":"public","relation":"part_of_dissertation","id":"13267"},{"status":"public","relation":"part_of_dissertation","id":"14257"}]},"_id":"18674","alternative_title":["ISTA Thesis"],"abstract":[{"lang":"eng","text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue requires volumetric imaging at nanoscale spatial resolution. While light microscopy excels at visualizing specific molecules and individual cells, achieving dense, synapse-level circuit reconstruction has not been possible with any light microscopy technique. Thus, the goal of my work was to develop image and data analysis pipelines for brain tissue visualization and reconstruction with light microscopy. To achieve dense circuit reconstruction with single-synapse resolution, I developed both conventional and deep-learning-based synapse detection algorithms, as well as connectivity analysis pipelines that integrate synapse detection with volumetric segmentation of brain tissue."}],"oa":1,"file_date_updated":"2024-12-18T14:41:53Z","language":[{"iso":"eng"}],"ec_funded":1},{"day":"08","project":[{"_id":"6285a163-2b32-11ec-9570-8e204ca2dba5","grant_number":"26137","name":"Studying Organelle Structure and Function at Nanoscale Resolution with Expansion Microscopy"},{"name":"International IST Doctoral Program","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"grant_number":"101044865","name":"Toward an understanding of the brain interstitial system and the extracellular proteome in health and autism spectrum disorders","_id":"34ba8964-11ca-11ed-8bc3-e15864e7e9a6"},{"name":"Molecular Drug Targets","grant_number":"W1232-B24","call_identifier":"FWF","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)"},"type":"preprint","publication_status":"draft","date_created":"2024-12-18T14:48:24Z","doi":"10.1101/2024.03.01.582884","department":[{"_id":"GaNo"},{"_id":"JoDa"}],"related_material":{"record":[{"status":"public","id":"18681","relation":"dissertation_contains"},{"status":"public","id":"18674","relation":"dissertation_contains"},{"relation":"later_version","id":"19704","status":"public"}]},"acknowledged_ssus":[{"_id":"E-Lib"},{"_id":"M-Shop"},{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"ScienComp"}],"citation":{"apa":"Tavakoli, M., Lyudchik, J., Januszewski, M., Vistunou, V., Agudelo Duenas, N., Vorlaufer, J., … Danzl, J. G. (n.d.). Light-microscopy based dense connectomic reconstruction of mammalian brain tissue. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/2024.03.01.582884\">https://doi.org/10.1101/2024.03.01.582884</a>","ama":"Tavakoli M, Lyudchik J, Januszewski M, et al. Light-microscopy based dense connectomic reconstruction of mammalian brain tissue. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2024.03.01.582884\">10.1101/2024.03.01.582884</a>","ista":"Tavakoli M, Lyudchik J, Januszewski M, Vistunou V, Agudelo Duenas N, Vorlaufer J, Sommer CM, Kreuzinger C, Oliveira B, Cenameri A, Novarino G, Jain V, Danzl JG. Light-microscopy based dense connectomic reconstruction of mammalian brain tissue. bioRxiv, <a href=\"https://doi.org/10.1101/2024.03.01.582884\">10.1101/2024.03.01.582884</a>.","chicago":"Tavakoli, Mojtaba, Julia Lyudchik, Michał Januszewski, Vitali Vistunou, Nathalie Agudelo Duenas, Jakob Vorlaufer, Christoph M Sommer, et al. “Light-Microscopy Based Dense Connectomic Reconstruction of Mammalian Brain Tissue.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.1101/2024.03.01.582884\">https://doi.org/10.1101/2024.03.01.582884</a>.","short":"M. Tavakoli, J. Lyudchik, M. Januszewski, V. Vistunou, N. Agudelo Duenas, J. Vorlaufer, C.M. Sommer, C. Kreuzinger, B. Oliveira, A. Cenameri, G. Novarino, V. Jain, J.G. Danzl, BioRxiv (n.d.).","mla":"Tavakoli, Mojtaba, et al. “Light-Microscopy Based Dense Connectomic Reconstruction of Mammalian Brain Tissue.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.1101/2024.03.01.582884\">10.1101/2024.03.01.582884</a>.","ieee":"M. Tavakoli <i>et al.</i>, “Light-microscopy based dense connectomic reconstruction of mammalian brain tissue,” <i>bioRxiv</i>. ."},"date_updated":"2026-04-28T13:33:34Z","_id":"18677","ec_funded":1,"language":[{"iso":"eng"}],"oa":1,"abstract":[{"text":"The information-processing capability of the brain’s cellular network depends on the physical wiring pattern between neurons and their molecular and functional characteristics. Mapping neurons and resolving their individual synaptic connections can be achieved by volumetric imaging at nanoscale resolution with dense cellular labeling. Light microscopy is uniquely positioned to visualize specific molecules but dense, synapse-level circuit reconstruction by light microscopy has been out of reach due to limitations in resolution, contrast, and volumetric imaging capability. Here we developed light-microscopy based connectomics (LICONN). We integrated specifically engineered hydrogel embedding and expansion with comprehensive deep-learning based segmentation and analysis of connectivity, thus directly incorporating molecular information in synapse-level brain tissue reconstructions. LICONN will allow synapse-level brain tissue phenotyping in biological experiments in a readily adoptable manner.","lang":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2024","date_published":"2024-07-08T00:00:00Z","oa_version":"Preprint","article_processing_charge":"No","title":"Light-microscopy based dense connectomic reconstruction of mammalian brain tissue","author":[{"last_name":"Tavakoli","full_name":"Tavakoli, Mojtaba","first_name":"Mojtaba","orcid":"0000-0002-7667-6854","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","full_name":"Lyudchik, Julia","last_name":"Lyudchik"},{"last_name":"Januszewski","first_name":"Michał","full_name":"Januszewski, Michał"},{"last_name":"Vistunou","first_name":"Vitali","full_name":"Vistunou, Vitali","id":"7e146587-8972-11ed-ae7b-d7a32ea86a81"},{"id":"40E7F008-F248-11E8-B48F-1D18A9856A87","last_name":"Agudelo Duenas","first_name":"Nathalie","full_name":"Agudelo Duenas, Nathalie"},{"id":"937696FA-C996-11E9-8C7C-CF13E6697425","orcid":"0009-0000-7590-3501","full_name":"Vorlaufer, Jakob","first_name":"Jakob","last_name":"Vorlaufer"},{"orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer","first_name":"Christoph M","full_name":"Sommer, Christoph M"},{"id":"382077BA-F248-11E8-B48F-1D18A9856A87","last_name":"Kreuzinger","full_name":"Kreuzinger, Caroline","first_name":"Caroline"},{"first_name":"Bárbara","full_name":"Oliveira, Bárbara","last_name":"Oliveira","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Cenameri","first_name":"Alban","full_name":"Cenameri, Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Jain","first_name":"Viren","full_name":"Jain, Viren"},{"full_name":"Danzl, Johann G","first_name":"Johann G","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973"}],"acknowledgement":"We thank Sven Dorkenwald and Peter Li for critical reading of the\r\nmanuscript. We acknowledge expert support by ISTA’s scientific service units: Imaging and\r\nOptics, Lab Support, Scientific Computing, Preclinical Facility, Miba Machine Shop, and Library.\r\nWe gratefully acknowledge funding by the following sources:\r\nAustrian Science Fund (FWF) grant DK W1232 (JGD, MRT)\r\nAustrian Academy of Sciences DOC fellowship 26137 (MRT)\r\nEU Horizon 2020 program, Marie Skłodowska-Curie Actions Fellowship 665385 (JL)\r\nGesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (JGD)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European Research\r\nCouncil (ERC) grant 101044865 “SecretAutism.”\r\n","main_file_link":[{"url":"https://doi.org/10.1101/2024.03.01.582884","open_access":"1"}],"month":"07","status":"public","corr_author":"1","OA_place":"repository","publication":"bioRxiv"},{"has_accepted_license":"1","status":"public","corr_author":"1","publisher":"Springer Nature","publication":"Nature Methods","OA_place":"publisher","publication_identifier":{"eissn":["1548-7105"],"issn":["1548-7091"]},"month":"08","intvolume":"        20","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.).","author":[{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431","full_name":"Velicky, Philipp","first_name":"Philipp","last_name":"Velicky"},{"last_name":"Miguel Villalba","full_name":"Miguel Villalba, Eder","first_name":"Eder","orcid":"0000-0001-5665-0430","id":"3FB91342-F248-11E8-B48F-1D18A9856A87"},{"id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3862-1235","first_name":"Julia M","full_name":"Michalska, Julia M","last_name":"Michalska"},{"last_name":"Lyudchik","full_name":"Lyudchik, Julia","first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Wei","first_name":"Donglai","full_name":"Wei, Donglai"},{"first_name":"Zudi","full_name":"Lin, Zudi","last_name":"Lin"},{"orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E","last_name":"Watson","first_name":"Jake","full_name":"Watson, Jake"},{"last_name":"Troidl","first_name":"Jakob","full_name":"Troidl, Jakob"},{"full_name":"Beyer, Johanna","first_name":"Johanna","last_name":"Beyer"},{"first_name":"Yoav","full_name":"Ben Simon, Yoav","last_name":"Ben Simon","id":"43DF3136-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Sommer, Christoph M","first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105"},{"id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0201-2315","full_name":"Jahr, Wiebke","first_name":"Wiebke","last_name":"Jahr"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban","full_name":"Cenameri, Alban","last_name":"Cenameri"},{"full_name":"Broichhagen, Johannes","first_name":"Johannes","last_name":"Broichhagen"},{"last_name":"Grant","full_name":"Grant, Seth G.N.","first_name":"Seth G.N."},{"last_name":"Jonas","first_name":"Peter M","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","full_name":"Novarino, Gaia","last_name":"Novarino"},{"full_name":"Pfister, Hanspeter","first_name":"Hanspeter","last_name":"Pfister"},{"first_name":"Bernd","full_name":"Bickel, Bernd","last_name":"Bickel","id":"49876194-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6511-9385"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","first_name":"Johann G","full_name":"Danzl, Johann G","last_name":"Danzl"}],"ddc":["570"],"external_id":{"pmid":["37429995"],"isi":["001025621500001"]},"page":"1256-1265","year":"2023","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"oa_version":"Published Version","date_published":"2023-08-01T00:00:00Z","volume":20,"article_processing_charge":"Yes (in subscription journal)","title":"Dense 4D nanoscale reconstruction of living brain tissue","OA_type":"hybrid","scopus_import":"1","ec_funded":1,"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."}],"oa":1,"file_date_updated":"2025-02-26T08:01:57Z","language":[{"iso":"eng"}],"related_material":{"record":[{"status":"public","id":"12817","relation":"research_data"},{"id":"14770","relation":"shorter_version","status":"public"},{"relation":"dissertation_contains","id":"18674","status":"public"},{"relation":"earlier_version","id":"11943","status":"public"}],"link":[{"relation":"software","url":"https://github.com/danzllab/LIONESS"}]},"citation":{"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.","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>.","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.","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>","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>","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."},"quality_controlled":"1","date_updated":"2026-07-06T12:49:46Z","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"E-Lib"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"_id":"13267","publication_status":"published","date_created":"2023-07-23T22:01:13Z","type":"journal_article","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"},{"_id":"Bio"}],"doi":"10.1038/s41592-023-01936-6","file":[{"content_type":"application/pdf","date_updated":"2025-02-26T08:01:57Z","file_name":"2023_NatureMethods_Velicky.pdf","checksum":"a68e845780a82ea36d0d4d3212a87c10","access_level":"open_access","success":1,"file_id":"19088","relation":"main_file","date_created":"2025-02-26T08:01:57Z","file_size":14103039,"creator":"dernst"}],"article_type":"original","isi":1,"day":"01","project":[{"grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232"},{"name":"Synaptic communication in neuronal microcircuits","grant_number":"Z00312","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"name":"High content imaging to decode human immune cell interactions in health and allergic disease","grant_number":"LS18-022","_id":"23889792-32DE-11EA-91FC-C7463DDC885E"},{"name":"International IST Doctoral Program","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"_id":"24F9549A-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling","grant_number":"715767"},{"_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"715508","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 glutamatergic synapse","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"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","grant_number":"LT00057","name":"High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration"}]},{"publication_identifier":{"issn":["2211-1247"]},"intvolume":"        39","month":"04","keyword":["General Biochemistry","Genetics and Molecular Biology"],"corr_author":"1","has_accepted_license":"1","status":"public","publication":"Cell Reports","publisher":"Elsevier","volume":39,"oa_version":"Published Version","pmid":1,"date_published":"2022-04-05T00:00:00Z","year":"2022","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","title":"CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories","article_processing_charge":"Yes","acknowledgement":"We thank Farnaz Freeman for technical assistance. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facility (BIF) and the Life Science Facility (LSF). This work supported by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 to G.N. (REVERSEAUTISM) and grant 825759 to G.T. (ENDpoiNTs); the Fondazione Cariplo 2017-0886 to A.L.T.; E-Rare-3 JTC 2018 IMPACT to M. Gabriele; and the Austrian Science Fund FWF I 4205-B to G.N. Graphical abstract and figures were created using BioRender.com.","author":[{"last_name":"Villa","full_name":"Villa, Carlo Emanuele","first_name":"Carlo Emanuele"},{"last_name":"Cheroni","full_name":"Cheroni, Cristina","first_name":"Cristina"},{"id":"4C66542E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9033-9096","full_name":"Dotter, Christoph","first_name":"Christoph","last_name":"Dotter"},{"full_name":"López-Tóbon, Alejandro","first_name":"Alejandro","last_name":"López-Tóbon"},{"first_name":"Bárbara","full_name":"Oliveira, Bárbara","last_name":"Oliveira","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87"},{"id":"42C9F57E-F248-11E8-B48F-1D18A9856A87","first_name":"Roberto","full_name":"Sacco, Roberto","last_name":"Sacco"},{"first_name":"Aysan Çerağ","full_name":"Yahya, Aysan Çerağ","last_name":"Yahya","id":"365A65F8-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Jasmin","full_name":"Morandell, Jasmin","last_name":"Morandell","id":"4739D480-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Gabriele, Michele","first_name":"Michele","last_name":"Gabriele"},{"id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7667-6854","first_name":"Mojtaba","full_name":"Tavakoli, Mojtaba","last_name":"Tavakoli"},{"last_name":"Lyudchik","full_name":"Lyudchik, Julia","first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","first_name":"Christoph M","last_name":"Sommer"},{"first_name":"Mariano","full_name":"Gabitto, Mariano","last_name":"Gabitto"},{"full_name":"Danzl, Johann G","first_name":"Johann G","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973"},{"full_name":"Testa, Giuseppe","first_name":"Giuseppe","last_name":"Testa"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","full_name":"Novarino, Gaia","last_name":"Novarino"}],"article_number":"110615","ddc":["570"],"external_id":{"isi":["000785983900003"],"pmid":["35385734"]},"citation":{"chicago":"Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon, Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” <i>Cell Reports</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">https://doi.org/10.1016/j.celrep.2022.110615</a>.","short":"C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco, A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer, M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022).","mla":"Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” <i>Cell Reports</i>, vol. 39, no. 1, 110615, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">10.1016/j.celrep.2022.110615</a>.","ieee":"C. E. Villa <i>et al.</i>, “CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories,” <i>Cell Reports</i>, vol. 39, no. 1. Elsevier, 2022.","apa":"Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco, R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">https://doi.org/10.1016/j.celrep.2022.110615</a>","ama":"Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. <i>Cell Reports</i>. 2022;39(1). doi:<a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">10.1016/j.celrep.2022.110615</a>","ista":"Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ, Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG, Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615."},"quality_controlled":"1","date_updated":"2026-07-08T22:30:05Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"related_material":{"record":[{"id":"18681","relation":"dissertation_contains","status":"public"},{"id":"18674","relation":"dissertation_contains","status":"public"},{"relation":"dissertation_contains","id":"12364","status":"public"}]},"issue":"1","_id":"11160","scopus_import":"1","abstract":[{"lang":"eng","text":"Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency affects neurodevelopmental is unclear. Here, employing human cerebral organoids, we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories with an accelerated and delayed generation of, respectively, inhibitory and excitatory neurons that yields, at days 60 and 120, symmetrically opposite expansions in their proportions. This imbalance is consistent with an enlargement of cerebral organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic design of patient-specific mutations and mosaic organoids, we define genotype-phenotype relationships and uncover their cell-autonomous nature. Our results define cell-type-specific CHD8-dependent molecular defects related to an abnormal program of proliferation and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations, our study uncovers reproducible developmental alterations that may be employed for neurodevelopmental disease modeling."}],"file_date_updated":"2022-04-15T09:06:25Z","oa":1,"language":[{"iso":"eng"}],"ec_funded":1,"article_type":"original","project":[{"grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"_id":"2690FEAC-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy","grant_number":"I04205"}],"isi":1,"day":"05","date_created":"2022-04-15T09:03:10Z","publication_status":"published","type":"journal_article","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"department":[{"_id":"JoDa"},{"_id":"GaNo"}],"doi":"10.1016/j.celrep.2022.110615","file":[{"date_updated":"2022-04-15T09:06:25Z","file_name":"2022_CellReports_Villa.pdf","checksum":"b4e8d68f0268dec499af333e6fd5d8e1","access_level":"open_access","success":1,"content_type":"application/pdf","date_created":"2022-04-15T09:06:25Z","file_size":"7808644","creator":"dernst","relation":"main_file","file_id":"11164"}]},{"department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"}],"doi":"10.1101/2022.08.17.504272","date_created":"2022-08-24T08:24:52Z","publication_status":"draft","author":[{"last_name":"Michalska","first_name":"Julia M","full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Julia","full_name":"Lyudchik, Julia","last_name":"Lyudchik","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431","first_name":"Philipp","full_name":"Velicky, Philipp","last_name":"Velicky"},{"id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","full_name":"Korinkova, Hana","first_name":"Hana","last_name":"Korinkova"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823","full_name":"Watson, Jake","first_name":"Jake","last_name":"Watson"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban","full_name":"Cenameri, Alban","last_name":"Cenameri"},{"full_name":"Sommer, Christoph M","first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105"},{"orcid":"0000-0003-2356-9403","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","last_name":"Venturino","first_name":"Alessandro","full_name":"Venturino, Alessandro"},{"full_name":"Roessler, Karl","first_name":"Karl","last_name":"Roessler"},{"first_name":"Thomas","full_name":"Czech, Thomas","last_name":"Czech"},{"orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","last_name":"Siegert","full_name":"Siegert, Sandra","first_name":"Sandra"},{"first_name":"Gaia","full_name":"Novarino, Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","first_name":"Peter M","full_name":"Jonas, Peter M","last_name":"Jonas"},{"last_name":"Danzl","first_name":"Johann G","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"}],"type":"preprint","title":"Uncovering brain tissue architecture across scales with super-resolution light microscopy","day":"18","article_processing_charge":"No","date_published":"2022-08-18T00:00:00Z","oa_version":"Preprint","year":"2022","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","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 nanoscopic synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS leverages fixation-compatible extracellular labeling and advanced optical readout, in particular stimulated-emission depletion and expansion microscopy, to comprehensively delineate cellular structures. It enables 3D-reconstructing single synapses and mapping synaptic connectivity by identification and tailored analysis of putative synaptic cleft regions. Applying CATS to the hippocampal mossy fiber circuitry, we demonstrate its power to reveal the system’s molecularly informed ultrastructure across spatial scales and assess local connectivity by reconstructing and quantifying the synaptic input and output structure of identified neurons."}],"publication":"bioRxiv","language":[{"iso":"eng"}],"oa":1,"das_tickbox":"1","corr_author":"1","status":"public","_id":"11950","month":"08","main_file_link":[{"url":"https://doi.org/10.1101/2022.08.17.504272","open_access":"1"}],"date_updated":"2026-07-08T22:31:24Z","citation":{"short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, A. Venturino, K. Roessler, T. Czech, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, BioRxiv (n.d.).","chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.1101/2022.08.17.504272\">https://doi.org/10.1101/2022.08.17.504272</a>.","ieee":"J. M. Michalska <i>et al.</i>, “Uncovering brain tissue architecture across scales with super-resolution light microscopy,” <i>bioRxiv</i>. .","mla":"Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>.","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture across scales with super-resolution light microscopy. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>","apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales with super-resolution light microscopy. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/2022.08.17.504272\">https://doi.org/10.1101/2022.08.17.504272</a>","ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv, <a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>."},"related_material":{"record":[{"relation":"dissertation_contains","id":"12470","status":"public"}]}}]