[{"date_created":"2023-09-24T22:01:11Z","file":[{"relation":"main_file","content_type":"application/pdf","creator":"dernst","file_id":"14497","success":1,"access_level":"open_access","date_updated":"2023-11-07T08:53:21Z","file_size":8197935,"file_name":"2023_iScience_Maes.pdf","checksum":"be1a560efdd96d20712311f4fc54aac2","date_created":"2023-11-07T08:53:21Z"}],"department":[{"_id":"SaSi"}],"has_accepted_license":"1","license":"https://creativecommons.org/licenses/by/4.0/","language":[{"iso":"eng"}],"scopus_import":"1","publisher":"Elsevier","date_published":"2023-10-20T00:00:00Z","article_type":"original","month":"10","file_date_updated":"2023-11-07T08:53:21Z","publication":"iScience","issue":"10","status":"public","intvolume":"        26","type":"journal_article","day":"20","ddc":["570"],"isi":1,"article_number":"107780","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"title":"Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout","external_id":{"pmid":["37731609"],"isi":["001080403500001"]},"doi":"10.1016/j.isci.2023.107780","year":"2023","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"quality_controlled":"1","oa_version":"Published Version","acknowledgement":"We thank the Scientific Service Units (SSU) of ISTA through resources provided by the Imaging and Optics Facility (IOF), the Lab Support Facility (LSF), and the Pre-Clinical Facility (PCF) team, specifically Sonja Haslinger and Michael Schunn for excellent mouse colony management and support. This research was supported by the FWF Sonderforschungsbereich F83 (to E.E.P). We thank Bálint Nagy, Ryan John A. Cubero, Marco Benevento and all members of the Siegert group for constant feedback on the project and article.","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_identifier":{"eissn":["2589-0042"]},"_id":"14363","pmid":1,"article_processing_charge":"Yes","oa":1,"date_updated":"2023-12-13T12:27:30Z","volume":26,"author":[{"orcid":"0000-0001-9642-1085","last_name":"Maes","full_name":"Maes, Margaret E","first_name":"Margaret E","id":"3838F452-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-9434-8902","full_name":"Colombo, Gloria","last_name":"Colombo","first_name":"Gloria","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87"},{"id":"3526230C-F248-11E8-B48F-1D18A9856A87","last_name":"Schoot Uiterkamp","full_name":"Schoot Uiterkamp, Florianne E","first_name":"Florianne E"},{"last_name":"Sternberg","full_name":"Sternberg, Felix","first_name":"Felix"},{"id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2356-9403","full_name":"Venturino, Alessandro","last_name":"Venturino","first_name":"Alessandro"},{"last_name":"Pohl","full_name":"Pohl, Elena E.","first_name":"Elena E."},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra","full_name":"Siegert, Sandra","last_name":"Siegert","orcid":"0000-0001-8635-0877"}],"abstract":[{"text":"Mitochondrial networks remodel their connectivity, content, and subcellular localization to support optimized energy production in conditions of increased environmental or cellular stress. Microglia rely on mitochondria to respond to these stressors, however our knowledge about mitochondrial networks and their adaptations in microglia in vivo is limited. Here, we generate a mouse model that selectively labels mitochondria in microglia. We identify that mitochondrial networks are more fragmented with increased content and perinuclear localization in vitro vs. in vivo. Mitochondrial networks adapt similarly in microglia closest to the injury site after optic nerve crush. Preventing microglial UCP2 increase after injury by selective knockout induces cellular stress. This results in mitochondrial hyperfusion in male microglia, a phenotype absent in females due to circulating estrogens. Our results establish the foundation for mitochondrial network analysis of microglia in vivo, emphasizing the importance of mitochondrial-based sex effects of microglia in other pathologies.","lang":"eng"}],"citation":{"ieee":"M. E. Maes <i>et al.</i>, “Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout,” <i>iScience</i>, vol. 26, no. 10. Elsevier, 2023.","apa":"Maes, M. E., Colombo, G., Schoot Uiterkamp, F. E., Sternberg, F., Venturino, A., Pohl, E. E., &#38; Siegert, S. (2023). Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout. <i>IScience</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.isci.2023.107780\">https://doi.org/10.1016/j.isci.2023.107780</a>","chicago":"Maes, Margaret E, Gloria Colombo, Florianne E Schoot Uiterkamp, Felix Sternberg, Alessandro Venturino, Elena E. Pohl, and Sandra Siegert. “Mitochondrial Network Adaptations of Microglia Reveal Sex-Specific Stress Response after Injury and UCP2 Knockout.” <i>IScience</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.isci.2023.107780\">https://doi.org/10.1016/j.isci.2023.107780</a>.","mla":"Maes, Margaret E., et al. “Mitochondrial Network Adaptations of Microglia Reveal Sex-Specific Stress Response after Injury and UCP2 Knockout.” <i>IScience</i>, vol. 26, no. 10, 107780, Elsevier, 2023, doi:<a href=\"https://doi.org/10.1016/j.isci.2023.107780\">10.1016/j.isci.2023.107780</a>.","ama":"Maes ME, Colombo G, Schoot Uiterkamp FE, et al. Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout. <i>iScience</i>. 2023;26(10). doi:<a href=\"https://doi.org/10.1016/j.isci.2023.107780\">10.1016/j.isci.2023.107780</a>","short":"M.E. Maes, G. Colombo, F.E. Schoot Uiterkamp, F. Sternberg, A. Venturino, E.E. Pohl, S. Siegert, IScience 26 (2023).","ista":"Maes ME, Colombo G, Schoot Uiterkamp FE, Sternberg F, Venturino A, Pohl EE, Siegert S. 2023. Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout. iScience. 26(10), 107780."},"publication_status":"published"},{"publication":"Nature Biotechnology","status":"public","day":"31","type":"journal_article","date_created":"2023-09-03T22:01:15Z","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"},{"_id":"Bio"},{"_id":"RySh"}],"scopus_import":"1","publisher":"Springer Nature","language":[{"iso":"eng"}],"month":"08","article_type":"original","date_published":"2023-08-31T00:00:00Z","publication_identifier":{"eissn":["1546-1696"],"issn":["1087-0156"]},"_id":"14257","quality_controlled":"1","oa_version":"Published Version","project":[{"grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"grant_number":"W1232-B24","_id":"2548AE96-B435-11E9-9278-68D0E5697425","name":"Molecular Drug Targets","call_identifier":"FWF"},{"grant_number":"Z00312","call_identifier":"FWF","name":"The Wittgenstein Prize","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"_id":"23889792-32DE-11EA-91FC-C7463DDC885E","name":"High content imaging to decode human immune cell interactions in health and allergic disease"},{"call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508"},{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program","call_identifier":"H2020","grant_number":"665385"},{"call_identifier":"H2020","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","name":"Synaptic computations of the hippocampal CA3 circuitry","grant_number":"101026635"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","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.).","article_processing_charge":"Yes (in subscription journal)","date_updated":"2024-02-21T12:18:18Z","oa":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."}],"author":[{"first_name":"Julia M","orcid":"0000-0003-3862-1235","full_name":"Michalska, Julia M","last_name":"Michalska","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","last_name":"Lyudchik","full_name":"Lyudchik, Julia"},{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","last_name":"Velicky","full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431","first_name":"Philipp"},{"first_name":"Hana","full_name":"Korinkova, Hana","last_name":"Korinkova","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","last_name":"Watson","full_name":"Watson, Jake","orcid":"0000-0002-8698-3823","first_name":"Jake"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban","last_name":"Cenameri","full_name":"Cenameri, Alban"},{"full_name":"Sommer, Christoph M","last_name":"Sommer","orcid":"0000-0003-1216-9105","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Amberg","full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207","first_name":"Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87"},{"id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","first_name":"Alessandro","last_name":"Venturino","full_name":"Venturino, Alessandro","orcid":"0000-0003-2356-9403"},{"first_name":"Karl","full_name":"Roessler, Karl","last_name":"Roessler"},{"first_name":"Thomas","last_name":"Czech","full_name":"Czech, Thomas"},{"first_name":"Romana","last_name":"Höftberger","full_name":"Höftberger, Romana"},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","last_name":"Siegert","full_name":"Siegert, Sandra","first_name":"Sandra"},{"full_name":"Novarino, Gaia","last_name":"Novarino","orcid":"0000-0002-7673-7178","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","last_name":"Jonas","orcid":"0000-0001-5001-4804","first_name":"Peter M"},{"full_name":"Danzl, Johann G","last_name":"Danzl","orcid":"0000-0001-8559-3973","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"}],"citation":{"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.","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>","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>.","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>","ieee":"J. M. Michalska <i>et al.</i>, “Imaging brain tissue architecture across millimeter to nanometer scales,” <i>Nature Biotechnology</i>. Springer Nature, 2023."},"publication_status":"epub_ahead","related_material":{"record":[{"status":"public","relation":"research_data","id":"13126"}],"link":[{"url":"https://github.com/danzllab/CATS","relation":"software"}]},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1038/s41587-023-01911-8"}],"isi":1,"external_id":{"isi":["001065254200001"]},"title":"Imaging brain tissue architecture across millimeter to nanometer scales","doi":"10.1038/s41587-023-01911-8","year":"2023","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"ec_funded":1},{"intvolume":"        25","status":"public","day":"15","type":"journal_article","issue":"7","publication":"iScience","file_date_updated":"2022-07-04T08:19:25Z","publisher":"Elsevier","scopus_import":"1","language":[{"iso":"eng"}],"month":"07","date_published":"2022-07-15T00:00:00Z","article_type":"original","date_created":"2022-07-03T22:01:33Z","file":[{"file_id":"11480","creator":"cchlebak","content_type":"application/pdf","relation":"main_file","success":1,"date_updated":"2022-07-04T08:19:25Z","access_level":"open_access","date_created":"2022-07-04T08:19:25Z","checksum":"a470b74e1b3796c710189c81a4cd4329","file_name":"2022_iScience_Bartalska.pdf","file_size":19400048}],"has_accepted_license":"1","department":[{"_id":"SaSi"}],"abstract":[{"lang":"eng","text":"Cerebral organoids differentiated from human-induced pluripotent stem cells (hiPSC) provide a unique opportunity to investigate brain development. However, organoids usually lack microglia, brain-resident immune cells, which are present in the early embryonic brain and participate in neuronal circuit development. Here, we find IBA1+ microglia-like cells alongside retinal cups between week 3 and 4 in 2.5D culture with an unguided retinal organoid differentiation protocol. Microglia do not infiltrate the neuroectoderm and instead enrich within non-pigmented, 3D-cystic compartments that develop in parallel to the 3D-retinal organoids. When we guide the retinal organoid differentiation with low-dosed BMP4, we prevent cup development and enhance microglia and 3D-cysts formation. Mass spectrometry identifies these 3D-cysts to express mesenchymal and epithelial markers. We confirmed this microglia-preferred environment also within the unguided protocol, providing insight into microglial behavior and migration and offer a model to study how they enter and distribute within the human brain."}],"author":[{"full_name":"Bartalska, Katarina","last_name":"Bartalska","first_name":"Katarina","id":"4D883232-F248-11E8-B48F-1D18A9856A87"},{"id":"32B7C918-F248-11E8-B48F-1D18A9856A87","first_name":"Verena","full_name":"Hübschmann, Verena","last_name":"Hübschmann"},{"last_name":"Korkut","full_name":"Korkut, Medina","orcid":"0000-0003-4309-2251","first_name":"Medina","id":"4B51CE74-F248-11E8-B48F-1D18A9856A87"},{"id":"850B2E12-9CD4-11E9-837F-E719E6697425","first_name":"Ryan J","orcid":"0000-0003-0002-1867","last_name":"Cubero","full_name":"Cubero, Ryan J"},{"last_name":"Venturino","full_name":"Venturino, Alessandro","orcid":"0000-0003-2356-9403","first_name":"Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Karl","last_name":"Rössler","full_name":"Rössler, Karl"},{"first_name":"Thomas","full_name":"Czech, Thomas","last_name":"Czech"},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","last_name":"Siegert","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877","first_name":"Sandra"}],"publication_status":"published","citation":{"chicago":"Bartalska, Katarina, Verena Hübschmann, Medina Korkut, Ryan J Cubero, Alessandro Venturino, Karl Rössler, Thomas Czech, and Sandra Siegert. “A Systematic Characterization of Microglia-like Cell Occurrence during Retinal Organoid Differentiation.” <i>IScience</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.isci.2022.104580\">https://doi.org/10.1016/j.isci.2022.104580</a>.","ieee":"K. Bartalska <i>et al.</i>, “A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation,” <i>iScience</i>, vol. 25, no. 7. Elsevier, 2022.","apa":"Bartalska, K., Hübschmann, V., Korkut, M., Cubero, R. J., Venturino, A., Rössler, K., … Siegert, S. (2022). A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation. <i>IScience</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.isci.2022.104580\">https://doi.org/10.1016/j.isci.2022.104580</a>","ista":"Bartalska K, Hübschmann V, Korkut M, Cubero RJ, Venturino A, Rössler K, Czech T, Siegert S. 2022. A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation. iScience. 25(7), 104580.","short":"K. Bartalska, V. Hübschmann, M. Korkut, R.J. Cubero, A. Venturino, K. Rössler, T. Czech, S. Siegert, IScience 25 (2022).","mla":"Bartalska, Katarina, et al. “A Systematic Characterization of Microglia-like Cell Occurrence during Retinal Organoid Differentiation.” <i>IScience</i>, vol. 25, no. 7, 104580, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.isci.2022.104580\">10.1016/j.isci.2022.104580</a>.","ama":"Bartalska K, Hübschmann V, Korkut M, et al. A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation. <i>iScience</i>. 2022;25(7). doi:<a href=\"https://doi.org/10.1016/j.isci.2022.104580\">10.1016/j.isci.2022.104580</a>"},"_id":"11478","publication_identifier":{"eissn":["2589-0042"]},"acknowledgement":"We thank the scientific service units at ISTA, specifically the lab support facility and imaging & optics facility for their support; Nicolas Armel for performing the Mass Spectrometry. We thank Alexandra Lang and Tanja Peilnsteiner for their help in human brain tissue collection, Rouven Schulz for his insights into the functional assays We thank all members of the Siegert group for constant feedback on the project and Margaret Maes, Rouven Schulz, and Marco Benevento for feedback on the manuscript. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant No. 715571 to S.S.) and from the Gesellschaft für Forschungsförderung Niederösterreich (grant No. Sc19-017 to V.H.).","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","quality_controlled":"1","project":[{"_id":"25D4A630-B435-11E9-9278-68D0E5697425","name":"Microglia action towards neuronal circuit formation and function in health and disease","call_identifier":"H2020","grant_number":"715571"},{"name":"IST Austria Open Access Fund","_id":"B67AFEDC-15C9-11EA-A837-991A96BB2854"},{"_id":"9B99D380-BA93-11EA-9121-9846C619BF3A","name":"How human microglia shape developing neurons during health and inflammation","grant_number":"SC19-017"}],"oa_version":"Published Version","volume":25,"oa":1,"date_updated":"2023-11-02T12:21:33Z","article_processing_charge":"Yes","title":"A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation","external_id":{"isi":["000830428500005"]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"year":"2022","doi":"10.1016/j.isci.2022.104580","ec_funded":1,"related_material":{"record":[{"relation":"other","id":"12117","status":"public"}]},"ddc":["610"],"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_number":"104580","isi":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 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.","lang":"eng"}],"status":"public","author":[{"first_name":"Julia M","orcid":"0000-0003-3862-1235","last_name":"Michalska","full_name":"Michalska, Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","last_name":"Lyudchik","full_name":"Lyudchik, Julia","first_name":"Julia"},{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","first_name":"Philipp","last_name":"Velicky","full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431"},{"full_name":"Korinkova, Hana","last_name":"Korinkova","first_name":"Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake","orcid":"0000-0002-8698-3823","full_name":"Watson, Jake","last_name":"Watson"},{"first_name":"Alban","full_name":"Cenameri, Alban","last_name":"Cenameri","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"first_name":"Christoph M","full_name":"Sommer, Christoph M","last_name":"Sommer","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Alessandro","last_name":"Venturino","full_name":"Venturino, Alessandro","orcid":"0000-0003-2356-9403","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Karl","full_name":"Roessler, Karl","last_name":"Roessler"},{"first_name":"Thomas","last_name":"Czech","full_name":"Czech, Thomas"},{"last_name":"Siegert","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Danzl","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"}],"publication_status":"submitted","citation":{"ieee":"J. M. Michalska <i>et al.</i>, “Uncovering brain tissue architecture across scales with super-resolution light microscopy,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","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>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2022.08.17.504272\">https://doi.org/10.1101/2022.08.17.504272</a>","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>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2022.08.17.504272\">https://doi.org/10.1101/2022.08.17.504272</a>.","mla":"Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, 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>","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.).","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>."},"day":"18","type":"preprint","_id":"11950","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Preprint","publication":"bioRxiv","oa":1,"date_updated":"2024-03-25T23:30:11Z","article_processing_charge":"No","publisher":"Cold Spring Harbor Laboratory","title":"Uncovering brain tissue architecture across scales with super-resolution light microscopy","language":[{"iso":"eng"}],"year":"2022","month":"08","doi":"10.1101/2022.08.17.504272","date_published":"2022-08-18T00:00:00Z","related_material":{"record":[{"status":"public","id":"12470","relation":"dissertation_contains"}]},"date_created":"2022-08-24T08:24:52Z","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"}],"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2022.08.17.504272"}]},{"scopus_import":"1","publisher":"Springer Nature","language":[{"iso":"eng"}],"month":"08","date_published":"2022-08-15T00:00:00Z","article_type":"original","file":[{"relation":"main_file","content_type":"application/pdf","creator":"cchlebak","file_id":"12002","success":1,"access_level":"open_access","date_updated":"2022-08-29T06:44:30Z","file_size":7317396,"file_name":"2022_NatComm_Schulz.pdf","checksum":"191d9db0266e14a28d3a56dc7f65da84","date_created":"2022-08-29T06:44:30Z"}],"date_created":"2022-08-28T22:01:59Z","has_accepted_license":"1","department":[{"_id":"SaSi"}],"intvolume":"        13","status":"public","day":"15","type":"journal_article","publication":"Nature Communications","file_date_updated":"2022-08-29T06:44:30Z","title":"Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses","external_id":{"isi":["000840984400032"],"pmid":["35970889"]},"year":"2022","doi":"10.1038/s41467-022-32390-1","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"LifeSc"}],"related_material":{"record":[{"status":"public","id":"11945","relation":"part_of_dissertation"},{"relation":"research_data","id":"11542","status":"public"}],"link":[{"url":"https://ista.ac.at/en/news/dreaddful-mimicry/","description":"News on ISTA website","relation":"press_release"}]},"ddc":["570"],"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_number":"4728","isi":1,"abstract":[{"lang":"eng","text":"G protein-coupled receptors (GPCRs) regulate processes ranging from immune responses to neuronal signaling. However, ligands for many GPCRs remain unknown, suffer from off-target effects or have poor bioavailability. Additionally, dissecting cell type-specific responses is challenging when the same GPCR is expressed on different cells within a tissue. Here, we overcome these limitations by engineering DREADD-based GPCR chimeras that bind clozapine-N-oxide and mimic a GPCR-of-interest. We show that chimeric DREADD-β2AR triggers responses comparable to β2AR on second messenger and kinase activity, post-translational modifications, and protein-protein interactions. Moreover, we successfully recapitulate β2AR-mediated filopodia formation in microglia, an immune cell capable of driving central nervous system inflammation. When dissecting microglial inflammation, we included two additional DREADD-based chimeras mimicking microglia-enriched GPR65 and GPR109A. DREADD-β2AR and DREADD-GPR65 modulate the inflammatory response with high similarity to endogenous β2AR, while DREADD-GPR109A shows no impact. Our DREADD-based approach allows investigation of cell type-dependent pathways without known endogenous ligands."}],"author":[{"id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5297-733X","last_name":"Schulz","full_name":"Schulz, Rouven","first_name":"Rouven"},{"first_name":"Medina","full_name":"Korkut, Medina","last_name":"Korkut","orcid":"0000-0003-4309-2251","id":"4B51CE74-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Venturino, Alessandro","last_name":"Venturino","orcid":"0000-0003-2356-9403","first_name":"Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","first_name":"Gloria","last_name":"Colombo","full_name":"Colombo, Gloria","orcid":"0000-0001-9434-8902"},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra","last_name":"Siegert","first_name":"Sandra"}],"citation":{"ista":"Schulz R, Korkut M, Venturino A, Colombo G, Siegert S. 2022. Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses. Nature Communications. 13, 4728.","short":"R. Schulz, M. Korkut, A. Venturino, G. Colombo, S. Siegert, Nature Communications 13 (2022).","ama":"Schulz R, Korkut M, Venturino A, Colombo G, Siegert S. Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses. <i>Nature Communications</i>. 2022;13. doi:<a href=\"https://doi.org/10.1038/s41467-022-32390-1\">10.1038/s41467-022-32390-1</a>","mla":"Schulz, Rouven, et al. “Chimeric GPCRs Mimic Distinct Signaling Pathways and Modulate Microglia Responses.” <i>Nature Communications</i>, vol. 13, 4728, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s41467-022-32390-1\">10.1038/s41467-022-32390-1</a>.","chicago":"Schulz, Rouven, Medina Korkut, Alessandro Venturino, Gloria Colombo, and Sandra Siegert. “Chimeric GPCRs Mimic Distinct Signaling Pathways and Modulate Microglia Responses.” <i>Nature Communications</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41467-022-32390-1\">https://doi.org/10.1038/s41467-022-32390-1</a>.","apa":"Schulz, R., Korkut, M., Venturino, A., Colombo, G., &#38; Siegert, S. (2022). Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-022-32390-1\">https://doi.org/10.1038/s41467-022-32390-1</a>","ieee":"R. Schulz, M. Korkut, A. Venturino, G. Colombo, and S. Siegert, “Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses,” <i>Nature Communications</i>, vol. 13. Springer Nature, 2022."},"publication_status":"published","publication_identifier":{"eissn":["2041-1723"]},"pmid":1,"_id":"11995","project":[{"name":"Modulating microglia through G protein-coupled receptor (GPCR) signaling","_id":"267F75D8-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","oa_version":"Published Version","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","acknowledgement":"The authors thank the Scientific Service Units at ISTA, in particular the Molecular Biology Service of the Lab Support Facility, Imaging & Optics Facility, and the Preclinical Facility, and the Novarino group, Harald Janoviak, and Marco Benevento for sharing reagents and expertise. This research was supported by a DOC Fellowship (24979) awarded to R.S. by the Austrian Academy of Sciences.","article_processing_charge":"No","volume":13,"oa":1,"date_updated":"2024-02-21T12:34:51Z"},{"citation":{"chicago":"Colombo, Gloria, Ryan J Cubero, Lida Kanari, Alessandro Venturino, Rouven Schulz, Martina Scolamiero, Jens Agerberg, et al. “A Tool for Mapping Microglial Morphology, MorphOMICs, Reveals Brain-Region and Sex-Dependent Phenotypes.” <i>Nature Neuroscience</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41593-022-01167-6\">https://doi.org/10.1038/s41593-022-01167-6</a>.","ieee":"G. Colombo <i>et al.</i>, “A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes,” <i>Nature Neuroscience</i>, vol. 25, no. 10. Springer Nature, pp. 1379–1393, 2022.","apa":"Colombo, G., Cubero, R. J., Kanari, L., Venturino, A., Schulz, R., Scolamiero, M., … Siegert, S. (2022). A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes. <i>Nature Neuroscience</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41593-022-01167-6\">https://doi.org/10.1038/s41593-022-01167-6</a>","ista":"Colombo G, Cubero RJ, Kanari L, Venturino A, Schulz R, Scolamiero M, Agerberg J, Mathys H, Tsai L-H, Chachólski W, Hess K, Siegert S. 2022. A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes. Nature Neuroscience. 25(10), 1379–1393.","short":"G. Colombo, R.J. Cubero, L. Kanari, A. Venturino, R. Schulz, M. Scolamiero, J. Agerberg, H. Mathys, L.-H. Tsai, W. Chachólski, K. Hess, S. Siegert, Nature Neuroscience 25 (2022) 1379–1393.","mla":"Colombo, Gloria, et al. “A Tool for Mapping Microglial Morphology, MorphOMICs, Reveals Brain-Region and Sex-Dependent Phenotypes.” <i>Nature Neuroscience</i>, vol. 25, no. 10, Springer Nature, 2022, pp. 1379–93, doi:<a href=\"https://doi.org/10.1038/s41593-022-01167-6\">10.1038/s41593-022-01167-6</a>.","ama":"Colombo G, Cubero RJ, Kanari L, et al. A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes. <i>Nature Neuroscience</i>. 2022;25(10):1379-1393. doi:<a href=\"https://doi.org/10.1038/s41593-022-01167-6\">10.1038/s41593-022-01167-6</a>"},"publication_status":"published","author":[{"id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","first_name":"Gloria","full_name":"Colombo, Gloria","last_name":"Colombo","orcid":"0000-0001-9434-8902"},{"id":"850B2E12-9CD4-11E9-837F-E719E6697425","last_name":"Cubero","full_name":"Cubero, Ryan J","orcid":"0000-0003-0002-1867","first_name":"Ryan J"},{"last_name":"Kanari","full_name":"Kanari, Lida","first_name":"Lida"},{"first_name":"Alessandro","orcid":"0000-0003-2356-9403","last_name":"Venturino","full_name":"Venturino, Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","full_name":"Schulz, Rouven","last_name":"Schulz","orcid":"0000-0001-5297-733X","first_name":"Rouven"},{"full_name":"Scolamiero, Martina","last_name":"Scolamiero","first_name":"Martina"},{"first_name":"Jens","full_name":"Agerberg, Jens","last_name":"Agerberg"},{"full_name":"Mathys, Hansruedi","last_name":"Mathys","first_name":"Hansruedi"},{"last_name":"Tsai","full_name":"Tsai, Li-Huei","first_name":"Li-Huei"},{"last_name":"Chachólski","full_name":"Chachólski, Wojciech","first_name":"Wojciech"},{"first_name":"Kathryn","last_name":"Hess","full_name":"Hess, Kathryn"},{"first_name":"Sandra","full_name":"Siegert, Sandra","last_name":"Siegert","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"}],"keyword":["General Neuroscience"],"abstract":[{"lang":"eng","text":"Environmental cues influence the highly dynamic morphology of microglia. Strategies to characterize these changes usually involve user-selected morphometric features, which preclude the identification of a spectrum of context-dependent morphological phenotypes. Here we develop MorphOMICs, a topological data analysis approach, which enables semiautomatic mapping of microglial morphology into an atlas of cue-dependent phenotypes and overcomes feature-selection biases and biological variability. We extract spatially heterogeneous and sexually dimorphic morphological phenotypes for seven adult mouse brain regions. This sex-specific phenotype declines with maturation but increases over the disease trajectories in two neurodegeneration mouse models, with females showing a faster morphological shift in affected brain regions. Remarkably, microglia morphologies reflect an adaptation upon repeated exposure to ketamine anesthesia and do not recover to control morphologies. Finally, we demonstrate that both long primary processes and short terminal processes provide distinct insights to morphological phenotypes. MorphOMICs opens a new perspective to characterize microglial morphology."}],"article_processing_charge":"No","oa":1,"date_updated":"2024-03-25T23:30:10Z","volume":25,"oa_version":"Published Version","project":[{"grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425","name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020"},{"call_identifier":"H2020","name":"Microglia action towards neuronal circuit formation and function in health and disease","_id":"25D4A630-B435-11E9-9278-68D0E5697425","grant_number":"715571"}],"quality_controlled":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","acknowledgement":"We thank the scientific service units at ISTA, in particular M. Schunn’s team at the preclinical facility, and especially our colony manager S. Haslinger, for excellent support. We are also grateful to the ISTA Imaging & Optics Facility, and in particular C. Sommer for helping with the data file conversions. We thank R. Erhart from the ISTA Scientific Computing Unit for improving the script performance. We thank M. Maes, B. Nagy, S. Oakeley and M. Benevento and all members of the Siegert group for constant feedback on the project and on the manuscript. This research was supported by the European Union Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Actions program (754411 to R.J.A.C.), and by the European Research Council (grant no. 715571 to S.S.). L.K. was supported by funding to the Blue Brain Project, a research center of the École polytechnique fédérale de Lausanne, from the Swiss government’s ETH Board of the Swiss Federal Institutes of Technology. L.-H.T. was supported by NIH (grant no. R37NS051874) and by the JPB Foundation. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.","publication_identifier":{"eissn":["1546-1726"],"issn":["1097-6256"]},"pmid":1,"_id":"12244","ec_funded":1,"year":"2022","doi":"10.1038/s41593-022-01167-6","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"ScienComp"}],"external_id":{"isi":["000862214700001"],"pmid":["36180790"]},"title":"A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes","isi":1,"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ddc":["570"],"related_material":{"link":[{"url":"https://ista.ac.at/en/news/morphomics-revealing-the-hidden-meaning-of-microglia-shape/","relation":"press_release","description":"News on ISTA website"}],"record":[{"status":"public","id":"12378","relation":"dissertation_contains"}]},"type":"journal_article","day":"01","status":"public","intvolume":"        25","page":"1379-1393","file_date_updated":"2023-01-30T08:06:56Z","publication":"Nature Neuroscience","issue":"10","date_published":"2022-10-01T00:00:00Z","article_type":"original","month":"10","language":[{"iso":"eng"}],"scopus_import":"1","publisher":"Springer Nature","department":[{"_id":"SaSi"}],"has_accepted_license":"1","date_created":"2023-01-16T09:53:07Z","file":[{"relation":"main_file","content_type":"application/pdf","creator":"dernst","file_id":"12437","success":1,"access_level":"open_access","date_updated":"2023-01-30T08:06:56Z","file_size":23789835,"file_name":"2022_NatureNeuroscience_Colombo.pdf","checksum":"28431146873096f52e0107b534f178c9","date_created":"2023-01-30T08:06:56Z"}]},{"issue":"1","publication":"Cell Reports","file_date_updated":"2021-07-19T13:32:17Z","intvolume":"        36","status":"public","day":"06","type":"journal_article","file":[{"success":1,"file_id":"9693","creator":"cziletti","relation":"main_file","content_type":"application/pdf","checksum":"f056255f6d01fd9a86b5387635928173","date_created":"2021-07-19T13:32:17Z","file_size":56388540,"file_name":"2021_CellReports_Venturino.pdf","access_level":"open_access","date_updated":"2021-07-19T13:32:17Z"}],"date_created":"2021-07-11T22:01:16Z","has_accepted_license":"1","department":[{"_id":"SaSi"}],"publisher":"Elsevier","scopus_import":"1","language":[{"iso":"eng"}],"month":"07","article_type":"original","date_published":"2021-07-06T00:00:00Z","pmid":1,"_id":"9642","publication_identifier":{"eissn":["22111247"]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","acknowledgement":"We thank the scientific service units at IST Austria, especially the IST bioimaging facility, the preclinical facility, and, specifically, Michael Schunn and Sonja Haslinger for excellent support; Plexxikon for the PLX food; the Csicsvari group for advice and equipment for in vivo recording; Jürgen Siegert for the light-entrainment design; Marco Benevento, Soledad Gonzalo Cogno, Pat King, and all Siegert group members for constant feedback on the project and manuscript; Lorena Pantano (PILM Bioinformatics Core) for assisting with sample-size determination for OD plasticity experiments; and Ana Morello from MIT for technical assistance with VEPs recordings. This research was supported by a DOC Fellowship from the Austrian Academy of Sciences at the Institute of Science and Technology Austria to R.S., from the European Union Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Actions program (grants 665385 to G.C.; 754411 to R.J.A.C.), the European Research Council (grant 715571 to S.S.), and the National Eye Institute of the National Institutes of Health under award numbers R01EY029245 (to M.F.B.) and R01EY023037 (diversity supplement to H.D.J-C.).","project":[{"call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program","grant_number":"665385"},{"name":"ISTplus - Postdoctoral Fellowships","_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"754411"},{"grant_number":"715571","call_identifier":"H2020","_id":"25D4A630-B435-11E9-9278-68D0E5697425","name":"Microglia action towards neuronal circuit formation and function in health and disease"}],"oa_version":"Published Version","quality_controlled":"1","volume":36,"date_updated":"2023-08-10T14:09:39Z","oa":1,"article_processing_charge":"No","abstract":[{"text":"Perineuronal nets (PNNs), components of the extracellular matrix, preferentially coat parvalbumin-positive interneurons and constrain critical-period plasticity in the adult cerebral cortex. Current strategies to remove PNN are long-lasting, invasive, and trigger neuropsychiatric symptoms. Here, we apply repeated anesthetic ketamine as a method with minimal behavioral effect. We find that this paradigm strongly reduces PNN coating in the healthy adult brain and promotes juvenile-like plasticity. Microglia are critically involved in PNN loss because they engage with parvalbumin-positive neurons in their defined cortical layer. We identify external 60-Hz light-flickering entrainment to recapitulate microglia-mediated PNN removal. Importantly, 40-Hz frequency, which is known to remove amyloid plaques, does not induce PNN loss, suggesting microglia might functionally tune to distinct brain frequencies. Thus, our 60-Hz light-entrainment strategy provides an alternative form of PNN intervention in the healthy adult brain.","lang":"eng"}],"author":[{"id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","last_name":"Venturino","full_name":"Venturino, Alessandro","orcid":"0000-0003-2356-9403","first_name":"Alessandro"},{"id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","first_name":"Rouven","orcid":"0000-0001-5297-733X","last_name":"Schulz","full_name":"Schulz, Rouven"},{"first_name":"Héctor","full_name":"De Jesús-Cortés, Héctor","last_name":"De Jesús-Cortés"},{"id":"3838F452-F248-11E8-B48F-1D18A9856A87","first_name":"Margaret E","last_name":"Maes","full_name":"Maes, Margaret E","orcid":"0000-0001-9642-1085"},{"full_name":"Nagy, Balint","last_name":"Nagy","first_name":"Balint","id":"93C65ECC-A6F2-11E9-8DF9-9712E6697425"},{"full_name":"Reilly-Andújar, Francis","last_name":"Reilly-Andújar","first_name":"Francis"},{"id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","first_name":"Gloria","last_name":"Colombo","full_name":"Colombo, Gloria","orcid":"0000-0001-9434-8902"},{"orcid":"0000-0003-0002-1867","full_name":"Cubero, Ryan J","last_name":"Cubero","first_name":"Ryan J","id":"850B2E12-9CD4-11E9-837F-E719E6697425"},{"id":"3526230C-F248-11E8-B48F-1D18A9856A87","first_name":"Florianne E","last_name":"Schoot Uiterkamp","full_name":"Schoot Uiterkamp, Florianne E"},{"first_name":"Mark F.","full_name":"Bear, Mark F.","last_name":"Bear"},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra","orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra","last_name":"Siegert"}],"publication_status":"published","citation":{"chicago":"Venturino, Alessandro, Rouven Schulz, Héctor De Jesús-Cortés, Margaret E Maes, Balint Nagy, Francis Reilly-Andújar, Gloria Colombo, et al. “Microglia Enable Mature Perineuronal Nets Disassembly upon Anesthetic Ketamine Exposure or 60-Hz Light Entrainment in the Healthy Brain.” <i>Cell Reports</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.celrep.2021.109313\">https://doi.org/10.1016/j.celrep.2021.109313</a>.","apa":"Venturino, A., Schulz, R., De Jesús-Cortés, H., Maes, M. E., Nagy, B., Reilly-Andújar, F., … Siegert, S. (2021). Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2021.109313\">https://doi.org/10.1016/j.celrep.2021.109313</a>","ieee":"A. Venturino <i>et al.</i>, “Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain,” <i>Cell Reports</i>, vol. 36, no. 1. Elsevier, 2021.","ista":"Venturino A, Schulz R, De Jesús-Cortés H, Maes ME, Nagy B, Reilly-Andújar F, Colombo G, Cubero RJ, Schoot Uiterkamp FE, Bear MF, Siegert S. 2021. Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain. Cell Reports. 36(1), 109313.","short":"A. Venturino, R. Schulz, H. De Jesús-Cortés, M.E. Maes, B. Nagy, F. Reilly-Andújar, G. Colombo, R.J. Cubero, F.E. Schoot Uiterkamp, M.F. Bear, S. Siegert, Cell Reports 36 (2021).","mla":"Venturino, Alessandro, et al. “Microglia Enable Mature Perineuronal Nets Disassembly upon Anesthetic Ketamine Exposure or 60-Hz Light Entrainment in the Healthy Brain.” <i>Cell Reports</i>, vol. 36, no. 1, 109313, Elsevier, 2021, doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109313\">10.1016/j.celrep.2021.109313</a>.","ama":"Venturino A, Schulz R, De Jesús-Cortés H, et al. Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain. <i>Cell Reports</i>. 2021;36(1). doi:<a href=\"https://doi.org/10.1016/j.celrep.2021.109313\">10.1016/j.celrep.2021.109313</a>"},"related_material":{"link":[{"url":"https://ist.ac.at/en/news/the-twinkle-and-the-brain/","description":"News on IST Homepage","relation":"press_release"}]},"ddc":["570"],"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"isi":1,"article_number":"109313","title":"Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain","external_id":{"isi":["000670188500004"],"pmid":["34233180"]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"doi":"10.1016/j.celrep.2021.109313","year":"2021","ec_funded":1},{"ddc":["573"],"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_number":"101012","title":"Minimally invasive protocols and quantification for microglia-mediated perineuronal net disassembly in mouse brain","acknowledged_ssus":[{"_id":"Bio"}],"year":"2021","doi":"10.1016/j.xpro.2021.101012","ec_funded":1,"_id":"10565","publication_identifier":{"eissn":["2666-1667"]},"acknowledgement":"This research was supported by the European Research Council (grant 715571 to S.S.). We thank Rouven Schulz, Michael Schunn, Claudia Gold, Gabriel Krens, Sarah Gorkiewicz, Margaret Maes, Jürgen Siegert, Marco Benevento, and Sara Oakeley for comments on the manuscript and the IST Austria Bioimaging Facility for the technical support.","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","quality_controlled":"1","project":[{"grant_number":"715571","call_identifier":"H2020","_id":"25D4A630-B435-11E9-9278-68D0E5697425","name":"Microglia action towards neuronal circuit formation and function in health and disease"}],"date_updated":"2023-11-16T13:11:04Z","oa":1,"volume":2,"article_processing_charge":"Yes","abstract":[{"lang":"eng","text":"Enzymatic digestion of the extracellular matrix with chondroitinase-ABC reinstates juvenile-like plasticity in the adult cortex as it also disassembles the perineuronal nets (PNNs). The disadvantage of the enzyme is that it must be applied intracerebrally and it degrades the ECM for several weeks. Here, we provide two minimally invasive and transient protocols for microglia-enabled PNN disassembly in mouse cortex: repeated treatment with ketamine-xylazine-acepromazine (KXA) anesthesia and 60-Hz light entrainment. We also discuss how to analyze PNNs within microglial endosomes-lysosomes. For complete details on the use and execution of this protocol, please refer to Venturino et al. (2021)."}],"author":[{"id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","full_name":"Venturino, Alessandro","last_name":"Venturino","orcid":"0000-0003-2356-9403","first_name":"Alessandro"},{"orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra","last_name":"Siegert","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"}],"publication_status":"published","citation":{"short":"A. Venturino, S. Siegert, STAR Protocols 2 (2021).","ista":"Venturino A, Siegert S. 2021. Minimally invasive protocols and quantification for microglia-mediated perineuronal net disassembly in mouse brain. STAR Protocols. 2(4), 101012.","ama":"Venturino A, Siegert S. Minimally invasive protocols and quantification for microglia-mediated perineuronal net disassembly in mouse brain. <i>STAR Protocols</i>. 2021;2(4). doi:<a href=\"https://doi.org/10.1016/j.xpro.2021.101012\">10.1016/j.xpro.2021.101012</a>","mla":"Venturino, Alessandro, and Sandra Siegert. “Minimally Invasive Protocols and Quantification for Microglia-Mediated Perineuronal Net Disassembly in Mouse Brain.” <i>STAR Protocols</i>, vol. 2, no. 4, 101012, Elsevier ; Cell Press, 2021, doi:<a href=\"https://doi.org/10.1016/j.xpro.2021.101012\">10.1016/j.xpro.2021.101012</a>.","chicago":"Venturino, Alessandro, and Sandra Siegert. “Minimally Invasive Protocols and Quantification for Microglia-Mediated Perineuronal Net Disassembly in Mouse Brain.” <i>STAR Protocols</i>. Elsevier ; Cell Press, 2021. <a href=\"https://doi.org/10.1016/j.xpro.2021.101012\">https://doi.org/10.1016/j.xpro.2021.101012</a>.","ieee":"A. Venturino and S. Siegert, “Minimally invasive protocols and quantification for microglia-mediated perineuronal net disassembly in mouse brain,” <i>STAR Protocols</i>, vol. 2, no. 4. Elsevier ; Cell Press, 2021.","apa":"Venturino, A., &#38; Siegert, S. (2021). Minimally invasive protocols and quantification for microglia-mediated perineuronal net disassembly in mouse brain. <i>STAR Protocols</i>. Elsevier ; Cell Press. <a href=\"https://doi.org/10.1016/j.xpro.2021.101012\">https://doi.org/10.1016/j.xpro.2021.101012</a>"},"file":[{"success":1,"creator":"cchlebak","file_id":"10570","content_type":"application/pdf","relation":"main_file","date_created":"2021-12-20T08:58:40Z","checksum":"9ea2501056c5df99e84726b845e9b976","file_name":"2021_STARProt_Venturino.pdf","file_size":6207060,"date_updated":"2021-12-20T08:58:40Z","access_level":"open_access"}],"date_created":"2021-12-19T23:01:32Z","has_accepted_license":"1","department":[{"_id":"SaSi"}],"publisher":"Elsevier ; Cell Press","scopus_import":"1","language":[{"iso":"eng"}],"month":"12","date_published":"2021-12-17T00:00:00Z","article_type":"original","issue":"4","publication":"STAR Protocols","file_date_updated":"2021-12-20T08:58:40Z","intvolume":"         2","status":"public","day":"17","type":"journal_article"}]