--- _id: '14363' abstract: - lang: eng 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. acknowledged_ssus: - _id: Bio - _id: LifeSc - _id: PreCl 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. article_number: '107780' article_processing_charge: Yes article_type: original author: - first_name: Margaret E full_name: Maes, Margaret E id: 3838F452-F248-11E8-B48F-1D18A9856A87 last_name: Maes orcid: 0000-0001-9642-1085 - first_name: Gloria full_name: Colombo, Gloria id: 3483CF6C-F248-11E8-B48F-1D18A9856A87 last_name: Colombo orcid: 0000-0001-9434-8902 - first_name: Florianne E full_name: Schoot Uiterkamp, Florianne E id: 3526230C-F248-11E8-B48F-1D18A9856A87 last_name: Schoot Uiterkamp - first_name: Felix full_name: Sternberg, Felix last_name: Sternberg - first_name: Alessandro full_name: Venturino, Alessandro id: 41CB84B2-F248-11E8-B48F-1D18A9856A87 last_name: Venturino orcid: 0000-0003-2356-9403 - first_name: Elena E. full_name: Pohl, Elena E. last_name: Pohl - first_name: Sandra full_name: Siegert, Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 citation: 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. iScience. 2023;26(10). doi:10.1016/j.isci.2023.107780 apa: Maes, M. E., Colombo, G., Schoot Uiterkamp, F. E., Sternberg, F., Venturino, A., Pohl, E. E., & Siegert, S. (2023). Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout. IScience. Elsevier. https://doi.org/10.1016/j.isci.2023.107780 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.” IScience. Elsevier, 2023. https://doi.org/10.1016/j.isci.2023.107780. ieee: M. E. Maes et al., “Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout,” iScience, vol. 26, no. 10. Elsevier, 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. mla: Maes, Margaret E., et al. “Mitochondrial Network Adaptations of Microglia Reveal Sex-Specific Stress Response after Injury and UCP2 Knockout.” IScience, vol. 26, no. 10, 107780, Elsevier, 2023, doi:10.1016/j.isci.2023.107780. short: M.E. Maes, G. Colombo, F.E. Schoot Uiterkamp, F. Sternberg, A. Venturino, E.E. Pohl, S. Siegert, IScience 26 (2023). date_created: 2023-09-24T22:01:11Z date_published: 2023-10-20T00:00:00Z date_updated: 2023-12-13T12:27:30Z day: '20' ddc: - '570' department: - _id: SaSi doi: 10.1016/j.isci.2023.107780 external_id: isi: - '001080403500001' pmid: - '37731609' file: - access_level: open_access checksum: be1a560efdd96d20712311f4fc54aac2 content_type: application/pdf creator: dernst date_created: 2023-11-07T08:53:21Z date_updated: 2023-11-07T08:53:21Z file_id: '14497' file_name: 2023_iScience_Maes.pdf file_size: 8197935 relation: main_file success: 1 file_date_updated: 2023-11-07T08:53:21Z has_accepted_license: '1' intvolume: ' 26' isi: 1 issue: '10' language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '10' oa: 1 oa_version: Published Version pmid: 1 publication: iScience publication_identifier: eissn: - 2589-0042 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Mitochondrial network adaptations of microglia reveal sex-specific stress response after injury and UCP2 knockout 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) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 26 year: '2023' ... --- _id: '14257' 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. acknowledged_ssus: - _id: ScienComp - _id: Bio - _id: PreCl - _id: LifeSc - _id: M-Shop - _id: E-Lib 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) article_type: original author: - first_name: Julia M full_name: Michalska, Julia M id: 443DB6DE-F248-11E8-B48F-1D18A9856A87 last_name: Michalska orcid: 0000-0003-3862-1235 - first_name: Julia full_name: Lyudchik, Julia id: 46E28B80-F248-11E8-B48F-1D18A9856A87 last_name: Lyudchik - first_name: Philipp full_name: Velicky, Philipp id: 39BDC62C-F248-11E8-B48F-1D18A9856A87 last_name: Velicky orcid: 0000-0002-2340-7431 - first_name: Hana full_name: Korinkova, Hana id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed last_name: Korinkova - first_name: Jake full_name: Watson, Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Alban full_name: Cenameri, Alban id: 9ac8f577-2357-11eb-997a-e566c5550886 last_name: Cenameri - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Nicole full_name: Amberg, Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Alessandro full_name: Venturino, Alessandro id: 41CB84B2-F248-11E8-B48F-1D18A9856A87 last_name: Venturino orcid: 0000-0003-2356-9403 - first_name: Karl full_name: Roessler, Karl last_name: Roessler - first_name: Thomas full_name: Czech, Thomas last_name: Czech - first_name: Romana full_name: Höftberger, Romana last_name: Höftberger - first_name: Sandra full_name: Siegert, Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 citation: ama: Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. 2023. doi:10.1038/s41587-023-01911-8 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. Nature Biotechnology. Springer Nature. https://doi.org/10.1038/s41587-023-01911-8 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.” Nature Biotechnology. Springer Nature, 2023. https://doi.org/10.1038/s41587-023-01911-8. ieee: J. M. Michalska et al., “Imaging brain tissue architecture across millimeter to nanometer scales,” Nature Biotechnology. Springer Nature, 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. mla: Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Nature Biotechnology, Springer Nature, 2023, doi:10.1038/s41587-023-01911-8. 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). date_created: 2023-09-03T22:01:15Z date_published: 2023-08-31T00:00:00Z date_updated: 2024-02-21T12:18:18Z day: '31' department: - _id: SaSi - _id: GaNo - _id: PeJo - _id: JoDa - _id: Bio - _id: RySh doi: 10.1038/s41587-023-01911-8 ec_funded: 1 external_id: isi: - '001065254200001' isi: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1038/s41587-023-01911-8 month: '08' oa: 1 oa_version: Published Version project: - _id: 265CB4D0-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03600 name: Optical control of synaptic function via adhesion molecules - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize - _id: 23889792-32DE-11EA-91FC-C7463DDC885E name: High content imaging to decode human immune cell interactions in health and allergic disease - _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 - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program - _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9 call_identifier: H2020 grant_number: '101026635' name: Synaptic computations of the hippocampal CA3 circuitry publication: Nature Biotechnology publication_identifier: eissn: - 1546-1696 issn: - 1087-0156 publication_status: epub_ahead publisher: Springer Nature quality_controlled: '1' related_material: link: - relation: software url: https://github.com/danzllab/CATS record: - id: '13126' relation: research_data status: public scopus_import: '1' status: public title: Imaging brain tissue architecture across millimeter to nanometer scales type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2023' ... --- _id: '11478' 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. acknowledged_ssus: - _id: Bio - _id: LifeSc 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.). article_number: '104580' article_processing_charge: Yes article_type: original author: - first_name: Katarina full_name: Bartalska, Katarina id: 4D883232-F248-11E8-B48F-1D18A9856A87 last_name: Bartalska - first_name: Verena full_name: Hübschmann, Verena id: 32B7C918-F248-11E8-B48F-1D18A9856A87 last_name: Hübschmann - first_name: Medina full_name: Korkut, Medina id: 4B51CE74-F248-11E8-B48F-1D18A9856A87 last_name: Korkut orcid: 0000-0003-4309-2251 - first_name: Ryan J full_name: Cubero, Ryan J id: 850B2E12-9CD4-11E9-837F-E719E6697425 last_name: Cubero orcid: 0000-0003-0002-1867 - first_name: Alessandro full_name: Venturino, Alessandro id: 41CB84B2-F248-11E8-B48F-1D18A9856A87 last_name: Venturino orcid: 0000-0003-2356-9403 - first_name: Karl full_name: Rössler, Karl last_name: Rössler - first_name: Thomas full_name: Czech, Thomas last_name: Czech - first_name: Sandra full_name: Siegert, Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 citation: ama: Bartalska K, Hübschmann V, Korkut M, et al. A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation. iScience. 2022;25(7). doi:10.1016/j.isci.2022.104580 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. IScience. Elsevier. https://doi.org/10.1016/j.isci.2022.104580 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.” IScience. Elsevier, 2022. https://doi.org/10.1016/j.isci.2022.104580. ieee: K. Bartalska et al., “A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation,” iScience, vol. 25, no. 7. Elsevier, 2022. 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. mla: Bartalska, Katarina, et al. “A Systematic Characterization of Microglia-like Cell Occurrence during Retinal Organoid Differentiation.” IScience, vol. 25, no. 7, 104580, Elsevier, 2022, doi:10.1016/j.isci.2022.104580. short: K. Bartalska, V. Hübschmann, M. Korkut, R.J. Cubero, A. Venturino, K. Rössler, T. Czech, S. Siegert, IScience 25 (2022). date_created: 2022-07-03T22:01:33Z date_published: 2022-07-15T00:00:00Z date_updated: 2023-11-02T12:21:33Z day: '15' ddc: - '610' department: - _id: SaSi doi: 10.1016/j.isci.2022.104580 ec_funded: 1 external_id: isi: - '000830428500005' file: - access_level: open_access checksum: a470b74e1b3796c710189c81a4cd4329 content_type: application/pdf creator: cchlebak date_created: 2022-07-04T08:19:25Z date_updated: 2022-07-04T08:19:25Z file_id: '11480' file_name: 2022_iScience_Bartalska.pdf file_size: 19400048 relation: main_file success: 1 file_date_updated: 2022-07-04T08:19:25Z has_accepted_license: '1' intvolume: ' 25' isi: 1 issue: '7' language: - iso: eng month: '07' oa: 1 oa_version: Published Version project: - _id: 25D4A630-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715571' name: Microglia action towards neuronal circuit formation and function in health and disease - _id: B67AFEDC-15C9-11EA-A837-991A96BB2854 name: IST Austria Open Access Fund - _id: 9B99D380-BA93-11EA-9121-9846C619BF3A grant_number: SC19-017 name: How human microglia shape developing neurons during health and inflammation publication: iScience publication_identifier: eissn: - 2589-0042 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: record: - id: '12117' relation: other status: public scopus_import: '1' status: public title: A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation 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) type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 25 year: '2022' ... --- _id: '12117' abstract: - lang: eng text: "To understand how potential gene manipulations affect in vitro microglia, we provide a set of short protocols to evaluate microglia identity and function. We detail steps for immunostaining to determine microglia identity. We describe three functional assays for microglia: phagocytosis, calcium response following ATP stimulation, and cytokine expression upon inflammatory stimuli. We apply these protocols to human induced-pluripotent-stem-cell (hiPSC)-derived microglia, but they can be also applied to other in vitro microglial models including primary mouse microglia.\r\nFor complete details on the use and execution of this protocol, please refer to Bartalska et al. (2022).1" acknowledged_ssus: - _id: Bio acknowledgement: 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.). We thank Rouven Schulz and Alessandro Venturino for their insights into functional assays and data analysis, Verena Seiboth for insights into necessary institutional permission, and ISTA imaging & optics facility (IOF) especially Bernhard Hochreiter for their support. article_number: '101866' article_processing_charge: No article_type: letter_note author: - first_name: Verena full_name: Hübschmann, Verena id: 32B7C918-F248-11E8-B48F-1D18A9856A87 last_name: Hübschmann - first_name: Medina full_name: Korkut, Medina id: 4B51CE74-F248-11E8-B48F-1D18A9856A87 last_name: Korkut orcid: 0000-0003-4309-2251 - first_name: Sandra full_name: Siegert, Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 citation: ama: Hübschmann V, Korkut M, Siegert S. Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay. STAR Protocols. 2022;3(4). doi:10.1016/j.xpro.2022.101866 apa: Hübschmann, V., Korkut, M., & Siegert, S. (2022). Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay. STAR Protocols. Elsevier. https://doi.org/10.1016/j.xpro.2022.101866 chicago: Hübschmann, Verena, Medina Korkut, and Sandra Siegert. “Assessing Human IPSC-Derived Microglia Identity and Function by Immunostaining, Phagocytosis, Calcium Activity, and Inflammation Assay.” STAR Protocols. Elsevier, 2022. https://doi.org/10.1016/j.xpro.2022.101866. ieee: V. Hübschmann, M. Korkut, and S. Siegert, “Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay,” STAR Protocols, vol. 3, no. 4. Elsevier, 2022. ista: Hübschmann V, Korkut M, Siegert S. 2022. Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay. STAR Protocols. 3(4), 101866. mla: Hübschmann, Verena, et al. “Assessing Human IPSC-Derived Microglia Identity and Function by Immunostaining, Phagocytosis, Calcium Activity, and Inflammation Assay.” STAR Protocols, vol. 3, no. 4, 101866, Elsevier, 2022, doi:10.1016/j.xpro.2022.101866. short: V. Hübschmann, M. Korkut, S. Siegert, STAR Protocols 3 (2022). date_created: 2023-01-12T11:56:38Z date_published: 2022-12-16T00:00:00Z date_updated: 2023-11-02T12:21:32Z day: '16' ddc: - '570' department: - _id: SaSi - _id: GradSch doi: 10.1016/j.xpro.2022.101866 ec_funded: 1 file: - access_level: open_access checksum: 3c71b8a60633d42c2f77c49025d5559b content_type: application/pdf creator: dernst date_created: 2023-01-23T09:50:51Z date_updated: 2023-01-23T09:50:51Z file_id: '12340' file_name: 2022_STARProtocols_Huebschmann.pdf file_size: 6251945 relation: main_file success: 1 file_date_updated: 2023-01-23T09:50:51Z has_accepted_license: '1' intvolume: ' 3' issue: '4' keyword: - General Immunology and Microbiology - General Biochemistry - Genetics and Molecular Biology - General Neuroscience language: - iso: eng license: https://creativecommons.org/licenses/by-nc-nd/4.0/ month: '12' oa: 1 oa_version: Published Version project: - _id: 25D4A630-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715571' name: Microglia action towards neuronal circuit formation and function in health and disease - _id: 9B99D380-BA93-11EA-9121-9846C619BF3A grant_number: SC19-017 name: How human microglia shape developing neurons during health and inflammation publication: STAR Protocols publication_identifier: issn: - 2666-1667 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: record: - id: '11478' relation: other status: public scopus_import: '1' status: public title: Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 3 year: '2022' ... --- _id: '11995' 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. acknowledged_ssus: - _id: PreCl - _id: Bio - _id: LifeSc 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_number: '4728' article_processing_charge: No article_type: original author: - first_name: Rouven full_name: Schulz, Rouven id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87 last_name: Schulz orcid: 0000-0001-5297-733X - first_name: Medina full_name: Korkut, Medina id: 4B51CE74-F248-11E8-B48F-1D18A9856A87 last_name: Korkut orcid: 0000-0003-4309-2251 - first_name: Alessandro full_name: Venturino, Alessandro id: 41CB84B2-F248-11E8-B48F-1D18A9856A87 last_name: Venturino orcid: 0000-0003-2356-9403 - first_name: Gloria full_name: Colombo, Gloria id: 3483CF6C-F248-11E8-B48F-1D18A9856A87 last_name: Colombo orcid: 0000-0001-9434-8902 - first_name: Sandra full_name: Siegert, Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 citation: ama: Schulz R, Korkut M, Venturino A, Colombo G, Siegert S. Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses. Nature Communications. 2022;13. doi:10.1038/s41467-022-32390-1 apa: Schulz, R., Korkut, M., Venturino, A., Colombo, G., & Siegert, S. (2022). Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-32390-1 chicago: Schulz, Rouven, Medina Korkut, Alessandro Venturino, Gloria Colombo, and Sandra Siegert. “Chimeric GPCRs Mimic Distinct Signaling Pathways and Modulate Microglia Responses.” Nature Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-32390-1. ieee: R. Schulz, M. Korkut, A. Venturino, G. Colombo, and S. Siegert, “Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses,” Nature Communications, vol. 13. Springer Nature, 2022. 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. mla: Schulz, Rouven, et al. “Chimeric GPCRs Mimic Distinct Signaling Pathways and Modulate Microglia Responses.” Nature Communications, vol. 13, 4728, Springer Nature, 2022, doi:10.1038/s41467-022-32390-1. short: R. Schulz, M. Korkut, A. Venturino, G. Colombo, S. Siegert, Nature Communications 13 (2022). date_created: 2022-08-28T22:01:59Z date_published: 2022-08-15T00:00:00Z date_updated: 2024-02-21T12:34:51Z day: '15' ddc: - '570' department: - _id: SaSi doi: 10.1038/s41467-022-32390-1 external_id: isi: - '000840984400032' pmid: - '35970889' file: - access_level: open_access checksum: 191d9db0266e14a28d3a56dc7f65da84 content_type: application/pdf creator: cchlebak date_created: 2022-08-29T06:44:30Z date_updated: 2022-08-29T06:44:30Z file_id: '12002' file_name: 2022_NatComm_Schulz.pdf file_size: 7317396 relation: main_file success: 1 file_date_updated: 2022-08-29T06:44:30Z has_accepted_license: '1' intvolume: ' 13' isi: 1 language: - iso: eng month: '08' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 267F75D8-B435-11E9-9278-68D0E5697425 name: Modulating microglia through G protein-coupled receptor (GPCR) signaling publication: Nature Communications publication_identifier: eissn: - 2041-1723 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - description: News on ISTA website relation: press_release url: https://ista.ac.at/en/news/dreaddful-mimicry/ record: - id: '11945' relation: part_of_dissertation status: public - id: '11542' relation: research_data status: public scopus_import: '1' status: public title: Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses 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) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 13 year: '2022' ... --- _id: '12244' 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. acknowledged_ssus: - _id: PreCl - _id: Bio - _id: ScienComp 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. article_processing_charge: No article_type: original author: - first_name: Gloria full_name: Colombo, Gloria id: 3483CF6C-F248-11E8-B48F-1D18A9856A87 last_name: Colombo orcid: 0000-0001-9434-8902 - first_name: Ryan J full_name: Cubero, Ryan J id: 850B2E12-9CD4-11E9-837F-E719E6697425 last_name: Cubero orcid: 0000-0003-0002-1867 - first_name: Lida full_name: Kanari, Lida last_name: Kanari - first_name: Alessandro full_name: Venturino, Alessandro id: 41CB84B2-F248-11E8-B48F-1D18A9856A87 last_name: Venturino orcid: 0000-0003-2356-9403 - first_name: Rouven full_name: Schulz, Rouven id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87 last_name: Schulz orcid: 0000-0001-5297-733X - first_name: Martina full_name: Scolamiero, Martina last_name: Scolamiero - first_name: Jens full_name: Agerberg, Jens last_name: Agerberg - first_name: Hansruedi full_name: Mathys, Hansruedi last_name: Mathys - first_name: Li-Huei full_name: Tsai, Li-Huei last_name: Tsai - first_name: Wojciech full_name: Chachólski, Wojciech last_name: Chachólski - first_name: Kathryn full_name: Hess, Kathryn last_name: Hess - first_name: Sandra full_name: Siegert, Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 citation: ama: Colombo G, Cubero RJ, Kanari L, et al. A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes. Nature Neuroscience. 2022;25(10):1379-1393. doi:10.1038/s41593-022-01167-6 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. Nature Neuroscience. Springer Nature. https://doi.org/10.1038/s41593-022-01167-6 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.” Nature Neuroscience. Springer Nature, 2022. https://doi.org/10.1038/s41593-022-01167-6. ieee: G. Colombo et al., “A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes,” Nature Neuroscience, vol. 25, no. 10. Springer Nature, pp. 1379–1393, 2022. 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. mla: Colombo, Gloria, et al. “A Tool for Mapping Microglial Morphology, MorphOMICs, Reveals Brain-Region and Sex-Dependent Phenotypes.” Nature Neuroscience, vol. 25, no. 10, Springer Nature, 2022, pp. 1379–93, doi:10.1038/s41593-022-01167-6. 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. date_created: 2023-01-16T09:53:07Z date_published: 2022-10-01T00:00:00Z date_updated: 2024-03-27T23:30:17Z day: '01' ddc: - '570' department: - _id: SaSi doi: 10.1038/s41593-022-01167-6 ec_funded: 1 external_id: isi: - '000862214700001' pmid: - '36180790' file: - access_level: open_access checksum: 28431146873096f52e0107b534f178c9 content_type: application/pdf creator: dernst date_created: 2023-01-30T08:06:56Z date_updated: 2023-01-30T08:06:56Z file_id: '12437' file_name: 2022_NatureNeuroscience_Colombo.pdf file_size: 23789835 relation: main_file success: 1 file_date_updated: 2023-01-30T08:06:56Z has_accepted_license: '1' intvolume: ' 25' isi: 1 issue: '10' keyword: - General Neuroscience language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: 1379-1393 pmid: 1 project: - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships - _id: 25D4A630-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715571' name: Microglia action towards neuronal circuit formation and function in health and disease publication: Nature Neuroscience publication_identifier: eissn: - 1546-1726 issn: - 1097-6256 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - description: News on ISTA website relation: press_release url: https://ista.ac.at/en/news/morphomics-revealing-the-hidden-meaning-of-microglia-shape/ record: - id: '12378' relation: dissertation_contains status: public scopus_import: '1' status: public title: A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes 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) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 25 year: '2022' ... --- _id: '11950' 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. article_processing_charge: No author: - first_name: Julia M full_name: Michalska, Julia M id: 443DB6DE-F248-11E8-B48F-1D18A9856A87 last_name: Michalska orcid: 0000-0003-3862-1235 - first_name: Julia full_name: Lyudchik, Julia id: 46E28B80-F248-11E8-B48F-1D18A9856A87 last_name: Lyudchik - first_name: Philipp full_name: Velicky, Philipp id: 39BDC62C-F248-11E8-B48F-1D18A9856A87 last_name: Velicky orcid: 0000-0002-2340-7431 - first_name: Hana full_name: Korinkova, Hana id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed last_name: Korinkova - first_name: Jake full_name: Watson, Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Alban full_name: Cenameri, Alban id: 9ac8f577-2357-11eb-997a-e566c5550886 last_name: Cenameri - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Alessandro full_name: Venturino, Alessandro id: 41CB84B2-F248-11E8-B48F-1D18A9856A87 last_name: Venturino orcid: 0000-0003-2356-9403 - first_name: Karl full_name: Roessler, Karl last_name: Roessler - first_name: Thomas full_name: Czech, Thomas last_name: Czech - first_name: Sandra full_name: Siegert, Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 citation: ama: Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv. doi:10.1101/2022.08.17.504272 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. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.08.17.504272 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.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2022.08.17.504272. ieee: J. M. Michalska et al., “Uncovering brain tissue architecture across scales with super-resolution light microscopy,” bioRxiv. Cold Spring Harbor Laboratory. 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, 10.1101/2022.08.17.504272. mla: Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2022.08.17.504272. 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.). date_created: 2022-08-24T08:24:52Z date_published: 2022-08-18T00:00:00Z date_updated: 2024-03-27T23:30:20Z day: '18' department: - _id: SaSi - _id: GaNo - _id: PeJo - _id: JoDa doi: 10.1101/2022.08.17.504272 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2022.08.17.504272 month: '08' oa: 1 oa_version: Preprint publication: bioRxiv publication_status: submitted publisher: Cold Spring Harbor Laboratory related_material: record: - id: '12470' relation: dissertation_contains status: public status: public title: Uncovering brain tissue architecture across scales with super-resolution light microscopy type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2022' ... --- _id: '9642' abstract: - lang: eng 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. acknowledged_ssus: - _id: Bio - _id: PreCl 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.). article_number: '109313' article_processing_charge: No article_type: original author: - first_name: Alessandro full_name: Venturino, Alessandro id: 41CB84B2-F248-11E8-B48F-1D18A9856A87 last_name: Venturino orcid: 0000-0003-2356-9403 - first_name: Rouven full_name: Schulz, Rouven id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87 last_name: Schulz orcid: 0000-0001-5297-733X - first_name: Héctor full_name: De Jesús-Cortés, Héctor last_name: De Jesús-Cortés - first_name: Margaret E full_name: Maes, Margaret E id: 3838F452-F248-11E8-B48F-1D18A9856A87 last_name: Maes orcid: 0000-0001-9642-1085 - first_name: Balint full_name: Nagy, Balint id: 93C65ECC-A6F2-11E9-8DF9-9712E6697425 last_name: Nagy - first_name: Francis full_name: Reilly-Andújar, Francis last_name: Reilly-Andújar - first_name: Gloria full_name: Colombo, Gloria id: 3483CF6C-F248-11E8-B48F-1D18A9856A87 last_name: Colombo orcid: 0000-0001-9434-8902 - first_name: Ryan J full_name: Cubero, Ryan J id: 850B2E12-9CD4-11E9-837F-E719E6697425 last_name: Cubero orcid: 0000-0003-0002-1867 - first_name: Florianne E full_name: Schoot Uiterkamp, Florianne E id: 3526230C-F248-11E8-B48F-1D18A9856A87 last_name: Schoot Uiterkamp - first_name: Mark F. full_name: Bear, Mark F. last_name: Bear - first_name: Sandra full_name: Siegert, Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 citation: 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. Cell Reports. 2021;36(1). doi:10.1016/j.celrep.2021.109313 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. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2021.109313 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.” Cell Reports. Elsevier, 2021. https://doi.org/10.1016/j.celrep.2021.109313. ieee: A. Venturino et al., “Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain,” Cell Reports, 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. mla: Venturino, Alessandro, et al. “Microglia Enable Mature Perineuronal Nets Disassembly upon Anesthetic Ketamine Exposure or 60-Hz Light Entrainment in the Healthy Brain.” Cell Reports, vol. 36, no. 1, 109313, Elsevier, 2021, doi:10.1016/j.celrep.2021.109313. 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). date_created: 2021-07-11T22:01:16Z date_published: 2021-07-06T00:00:00Z date_updated: 2023-08-10T14:09:39Z day: '06' ddc: - '570' department: - _id: SaSi doi: 10.1016/j.celrep.2021.109313 ec_funded: 1 external_id: isi: - '000670188500004' pmid: - '34233180' file: - access_level: open_access checksum: f056255f6d01fd9a86b5387635928173 content_type: application/pdf creator: cziletti date_created: 2021-07-19T13:32:17Z date_updated: 2021-07-19T13:32:17Z file_id: '9693' file_name: 2021_CellReports_Venturino.pdf file_size: 56388540 relation: main_file success: 1 file_date_updated: 2021-07-19T13:32:17Z has_accepted_license: '1' intvolume: ' 36' isi: 1 issue: '1' language: - iso: eng month: '07' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships - _id: 25D4A630-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715571' name: Microglia action towards neuronal circuit formation and function in health and disease publication: Cell Reports publication_identifier: eissn: - '22111247' publication_status: published publisher: Elsevier quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/the-twinkle-and-the-brain/ scopus_import: '1' status: public title: Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain 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) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 36 year: '2021' ... --- _id: '10655' abstract: - lang: eng text: "Adeno-associated viruses (AAVs) are widely used to deliver genetic material in vivo to distinct cell types such as neurons or glial cells, allowing for targeted manipulation. Transduction of microglia is mostly excluded from this strategy, likely due to the cells’ heterogeneous state upon environmental changes, which makes AAV design challenging. Here, we established the retina as a model system for microglial AAV validation and optimization. First, we show that AAV2/6 transduced microglia in both synaptic layers, where layer preference corresponds to the intravitreal or subretinal delivery method. Surprisingly, we observed significantly enhanced microglial transduction during photoreceptor degeneration. Thus, we modified the AAV6 capsid to reduce heparin binding by introducing four point mutations (K531E, R576Q, K493S, and K459S), resulting in increased microglial transduction in the outer plexiform layer. Finally, to improve microglial-specific transduction, we validated a Cre-dependent transgene delivery cassette for use in combination with the Cx3cr1CreERT2 mouse line. Together, our results provide a foundation for future studies optimizing AAV-mediated microglia transduction and highlight that environmental conditions influence microglial transduction efficiency.\r\n" acknowledged_ssus: - _id: Bio - _id: LifeSc - _id: PreCl acknowledgement: This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 715571). The research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facility, the Life Science Facility, and the Pre-Clinical Facility, namely Sonja Haslinger and Michael Schunn for their animal colony management and support. We would also like to thank Chakrabarty Lab for sharing the plasmids for AAV2/6 production. Finally, we would like to thank the Siegert team members for discussion about the manuscript. article_processing_charge: Yes article_type: original author: - first_name: Margaret E full_name: Maes, Margaret E id: 3838F452-F248-11E8-B48F-1D18A9856A87 last_name: Maes orcid: 0000-0001-9642-1085 - first_name: Gabriele M. full_name: Wögenstein, Gabriele M. last_name: Wögenstein - first_name: Gloria full_name: Colombo, Gloria id: 3483CF6C-F248-11E8-B48F-1D18A9856A87 last_name: Colombo orcid: 0000-0001-9434-8902 - first_name: Raquel full_name: Casado Polanco, Raquel id: 15240fc1-dbcd-11ea-9d1d-ac5a786425fd last_name: Casado Polanco orcid: 0000-0001-8293-4568 - first_name: Sandra full_name: Siegert, Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 citation: ama: Maes ME, Wögenstein GM, Colombo G, Casado Polanco R, Siegert S. Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment. Molecular Therapy - Methods and Clinical Development. 2021;23:210-224. doi:10.1016/j.omtm.2021.09.006 apa: Maes, M. E., Wögenstein, G. M., Colombo, G., Casado Polanco, R., & Siegert, S. (2021). Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment. Molecular Therapy - Methods and Clinical Development. Elsevier. https://doi.org/10.1016/j.omtm.2021.09.006 chicago: Maes, Margaret E, Gabriele M. Wögenstein, Gloria Colombo, Raquel Casado Polanco, and Sandra Siegert. “Optimizing AAV2/6 Microglial Targeting Identified Enhanced Efficiency in the Photoreceptor Degenerative Environment.” Molecular Therapy - Methods and Clinical Development. Elsevier, 2021. https://doi.org/10.1016/j.omtm.2021.09.006. ieee: M. E. Maes, G. M. Wögenstein, G. Colombo, R. Casado Polanco, and S. Siegert, “Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment,” Molecular Therapy - Methods and Clinical Development, vol. 23. Elsevier, pp. 210–224, 2021. ista: Maes ME, Wögenstein GM, Colombo G, Casado Polanco R, Siegert S. 2021. Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment. Molecular Therapy - Methods and Clinical Development. 23, 210–224. mla: Maes, Margaret E., et al. “Optimizing AAV2/6 Microglial Targeting Identified Enhanced Efficiency in the Photoreceptor Degenerative Environment.” Molecular Therapy - Methods and Clinical Development, vol. 23, Elsevier, 2021, pp. 210–24, doi:10.1016/j.omtm.2021.09.006. short: M.E. Maes, G.M. Wögenstein, G. Colombo, R. Casado Polanco, S. Siegert, Molecular Therapy - Methods and Clinical Development 23 (2021) 210–224. date_created: 2022-01-23T23:01:28Z date_published: 2021-12-10T00:00:00Z date_updated: 2023-11-16T13:12:03Z day: '10' ddc: - '570' department: - _id: SaSi - _id: SiHi doi: 10.1016/j.omtm.2021.09.006 ec_funded: 1 external_id: isi: - '000748748500019' file: - access_level: open_access checksum: 77dc540e8011c5475031bdf6ccef20a6 content_type: application/pdf creator: cchlebak date_created: 2022-01-24T07:43:09Z date_updated: 2022-01-24T07:43:09Z file_id: '10657' file_name: 2021_MolTherMethodsClinDev_Maes.pdf file_size: 4794147 relation: main_file success: 1 file_date_updated: 2022-01-24T07:43:09Z has_accepted_license: '1' intvolume: ' 23' isi: 1 language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: 210-224 project: - _id: 25D4A630-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715571' name: Microglia action towards neuronal circuit formation and function in health and disease publication: Molecular Therapy - Methods and Clinical Development publication_identifier: eissn: - 2329-0501 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment 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) type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 23 year: '2021' ... --- _id: '10565' 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).' acknowledged_ssus: - _id: Bio 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. article_number: '101012' article_processing_charge: Yes article_type: original author: - first_name: Alessandro full_name: Venturino, Alessandro id: 41CB84B2-F248-11E8-B48F-1D18A9856A87 last_name: Venturino orcid: 0000-0003-2356-9403 - first_name: Sandra full_name: Siegert, Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 citation: ama: Venturino A, Siegert S. Minimally invasive protocols and quantification for microglia-mediated perineuronal net disassembly in mouse brain. STAR Protocols. 2021;2(4). doi:10.1016/j.xpro.2021.101012 apa: Venturino, A., & Siegert, S. (2021). Minimally invasive protocols and quantification for microglia-mediated perineuronal net disassembly in mouse brain. STAR Protocols. Elsevier ; Cell Press. https://doi.org/10.1016/j.xpro.2021.101012 chicago: Venturino, Alessandro, and Sandra Siegert. “Minimally Invasive Protocols and Quantification for Microglia-Mediated Perineuronal Net Disassembly in Mouse Brain.” STAR Protocols. Elsevier ; Cell Press, 2021. https://doi.org/10.1016/j.xpro.2021.101012. ieee: A. Venturino and S. Siegert, “Minimally invasive protocols and quantification for microglia-mediated perineuronal net disassembly in mouse brain,” STAR Protocols, vol. 2, no. 4. Elsevier ; Cell Press, 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. mla: Venturino, Alessandro, and Sandra Siegert. “Minimally Invasive Protocols and Quantification for Microglia-Mediated Perineuronal Net Disassembly in Mouse Brain.” STAR Protocols, vol. 2, no. 4, 101012, Elsevier ; Cell Press, 2021, doi:10.1016/j.xpro.2021.101012. short: A. Venturino, S. Siegert, STAR Protocols 2 (2021). date_created: 2021-12-19T23:01:32Z date_published: 2021-12-17T00:00:00Z date_updated: 2023-11-16T13:11:04Z day: '17' ddc: - '573' department: - _id: SaSi doi: 10.1016/j.xpro.2021.101012 ec_funded: 1 file: - access_level: open_access checksum: 9ea2501056c5df99e84726b845e9b976 content_type: application/pdf creator: cchlebak date_created: 2021-12-20T08:58:40Z date_updated: 2021-12-20T08:58:40Z file_id: '10570' file_name: 2021_STARProt_Venturino.pdf file_size: 6207060 relation: main_file success: 1 file_date_updated: 2021-12-20T08:58:40Z has_accepted_license: '1' intvolume: ' 2' issue: '4' language: - iso: eng month: '12' oa: 1 oa_version: Published Version project: - _id: 25D4A630-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715571' name: Microglia action towards neuronal circuit formation and function in health and disease publication: STAR Protocols publication_identifier: eissn: - 2666-1667 publication_status: published publisher: Elsevier ; Cell Press quality_controlled: '1' scopus_import: '1' status: public title: Minimally invasive protocols and quantification for microglia-mediated perineuronal net disassembly in mouse brain 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) type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 2 year: '2021' ... --- _id: '6521' abstract: - lang: eng text: Microglia have emerged as a critical component of neurodegenerative diseases. Genetic manipulation of microglia can elucidate their functional impact in disease. In neuroscience, recombinant viruses such as lentiviruses and adeno-associated viruses (AAVs) have been successfully used to target various cell types in the brain, although effective transduction of microglia is rare. In this review, we provide a short background of lentiviruses and AAVs, and strategies for designing recombinant viral vectors. Then, we will summarize recent literature on successful microglial transductions in vitro and in vivo, and discuss the current challenges. Finally, we provide guidelines for reporting the efficiency and specificity of viral targeting in microglia, which will enable the microglial research community to assess and improve methodologies for future studies. article_number: '134310' article_processing_charge: No article_type: original author: - first_name: Margaret E full_name: Maes, Margaret E id: 3838F452-F248-11E8-B48F-1D18A9856A87 last_name: Maes orcid: 0000-0001-9642-1085 - first_name: Gloria full_name: Colombo, Gloria id: 3483CF6C-F248-11E8-B48F-1D18A9856A87 last_name: Colombo orcid: 0000-0001-9434-8902 - first_name: Rouven full_name: Schulz, Rouven id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87 last_name: Schulz orcid: 0000-0001-5297-733X - first_name: Sandra full_name: Siegert, Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 citation: ama: 'Maes ME, Colombo G, Schulz R, Siegert S. Targeting microglia with lentivirus and AAV: Recent advances and remaining challenges. Neuroscience Letters. 2019;707. doi:10.1016/j.neulet.2019.134310' apa: 'Maes, M. E., Colombo, G., Schulz, R., & Siegert, S. (2019). Targeting microglia with lentivirus and AAV: Recent advances and remaining challenges. Neuroscience Letters. Elsevier. https://doi.org/10.1016/j.neulet.2019.134310' chicago: 'Maes, Margaret E, Gloria Colombo, Rouven Schulz, and Sandra Siegert. “Targeting Microglia with Lentivirus and AAV: Recent Advances and Remaining Challenges.” Neuroscience Letters. Elsevier, 2019. https://doi.org/10.1016/j.neulet.2019.134310.' ieee: 'M. E. Maes, G. Colombo, R. Schulz, and S. Siegert, “Targeting microglia with lentivirus and AAV: Recent advances and remaining challenges,” Neuroscience Letters, vol. 707. Elsevier, 2019.' ista: 'Maes ME, Colombo G, Schulz R, Siegert S. 2019. Targeting microglia with lentivirus and AAV: Recent advances and remaining challenges. Neuroscience Letters. 707, 134310.' mla: 'Maes, Margaret E., et al. “Targeting Microglia with Lentivirus and AAV: Recent Advances and Remaining Challenges.” Neuroscience Letters, vol. 707, 134310, Elsevier, 2019, doi:10.1016/j.neulet.2019.134310.' short: M.E. Maes, G. Colombo, R. Schulz, S. Siegert, Neuroscience Letters 707 (2019). date_created: 2019-06-05T13:16:24Z date_published: 2019-08-10T00:00:00Z date_updated: 2023-08-28T09:30:57Z day: '10' ddc: - '570' department: - _id: SaSi doi: 10.1016/j.neulet.2019.134310 ec_funded: 1 external_id: isi: - '000486094600037' pmid: - '31158432' file: - access_level: open_access checksum: 553c9dbd39727fbed55ee991c51ca4d1 content_type: application/pdf creator: dernst date_created: 2019-06-08T11:44:20Z date_updated: 2020-07-14T12:47:33Z file_id: '6551' file_name: 2019_Neuroscience_Maes.pdf file_size: 1779287 relation: main_file file_date_updated: 2020-07-14T12:47:33Z has_accepted_license: '1' intvolume: ' 707' isi: 1 language: - iso: eng month: '08' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program - _id: 25D4A630-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715571' name: Microglia action towards neuronal circuit formation and function in health and disease - _id: 267F75D8-B435-11E9-9278-68D0E5697425 name: Modulating microglia through G protein-coupled receptor (GPCR) signaling publication: Neuroscience Letters publication_identifier: issn: - 0304-3940 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: 'Targeting microglia with lentivirus and AAV: Recent advances and remaining challenges' 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) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 707 year: '2019' ... --- _id: '1613' abstract: - lang: eng text: "In the last decade, induced pluripotent stem (iPS) cells have revolutionized the utility of human in vitro models of neurological disease. The iPS-derived and differentiated cells allow researchers to study the impact of a distinct cell type in health and disease as well as performing therapeutic drug screens on a human genetic background. In particular, clinical trials for Alzheimer's disease (AD) have been often failing. Two of the potential reasons are first, the species gap involved in proceeding from initial discoveries in rodent models to human studies, and second, an unsatisfying patient stratification, meaning subgrouping patients based on the disease severity due to the lack of phenotypic and genetic markers. iPS cells overcome this obstacles and will improve our understanding of disease subtypes in AD. They allow researchers conducting in depth characterization of neural cells from both familial and sporadic AD patients as well as preclinical screens on human cells.\r\n\r\nIn this review, we briefly outline the status quo of iPS cell research in neurological diseases along with the general advantages and pitfalls of these models. We summarize how genome-editing techniques such as CRISPR/Cas will allow researchers to reduce the problem of genomic variability inherent to human studies, followed by recent iPS cell studies relevant to AD. We then focus on current techniques for the differentiation of iPS cells into neural cell types that are relevant to AD research. Finally, we discuss how the generation of three-dimensional cell culture systems will be important for understanding AD phenotypes in a complex cellular milieu, and how both two- and three-dimensional iPS cell models can provide platforms for drug discovery and translational studies into the treatment of AD." acknowledgement: This work was supported by NIH grant R01-AG047661 to LHT. The art in Fig. 1 was created by Julian Wong. author: - first_name: Alison full_name: Mungenast, Alison last_name: Mungenast - first_name: Sandra full_name: Siegert, Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 - first_name: Li full_name: Tsai, Li last_name: Tsai citation: ama: Mungenast A, Siegert S, Tsai L. Modeling Alzheimer’s disease with human induced pluripotent stem (iPS) cells. Molecular and Cellular Neuroscience. 2016;73:13-31. doi:doi:10.1016/j.mcn.2015.11.010 apa: Mungenast, A., Siegert, S., & Tsai, L. (2016). Modeling Alzheimer’s disease with human induced pluripotent stem (iPS) cells. Molecular and Cellular Neuroscience. Academic Press. https://doi.org/doi:10.1016/j.mcn.2015.11.010 chicago: Mungenast, Alison, Sandra Siegert, and Li Tsai. “Modeling Alzheimer’s Disease with Human Induced Pluripotent Stem (IPS) Cells.” Molecular and Cellular Neuroscience. Academic Press, 2016. https://doi.org/doi:10.1016/j.mcn.2015.11.010. ieee: A. Mungenast, S. Siegert, and L. Tsai, “Modeling Alzheimer’s disease with human induced pluripotent stem (iPS) cells,” Molecular and Cellular Neuroscience, vol. 73. Academic Press, pp. 13–31, 2016. ista: Mungenast A, Siegert S, Tsai L. 2016. Modeling Alzheimer’s disease with human induced pluripotent stem (iPS) cells. Molecular and Cellular Neuroscience. 73, 13–31. mla: Mungenast, Alison, et al. “Modeling Alzheimer’s Disease with Human Induced Pluripotent Stem (IPS) Cells.” Molecular and Cellular Neuroscience, vol. 73, Academic Press, 2016, pp. 13–31, doi:doi:10.1016/j.mcn.2015.11.010. short: A. Mungenast, S. Siegert, L. Tsai, Molecular and Cellular Neuroscience 73 (2016) 13–31. date_created: 2018-12-11T11:53:02Z date_published: 2016-06-01T00:00:00Z date_updated: 2021-01-12T06:52:00Z day: '01' ddc: - '616' doi: doi:10.1016/j.mcn.2015.11.010 extern: '1' file: - access_level: open_access checksum: 620254114e04d5d6e7f37d15e4b8ace4 content_type: application/pdf creator: system date_created: 2018-12-12T10:12:50Z date_updated: 2020-07-14T12:45:07Z file_id: '4970' file_name: IST-2018-979-v1+1_Mungenast_2015_acceptedManuscript.pdf file_size: 632915 relation: main_file file_date_updated: 2020-07-14T12:45:07Z has_accepted_license: '1' intvolume: ' 73' language: - iso: eng month: '06' oa: 1 oa_version: Submitted Version page: 13 - 31 publication: Molecular and Cellular Neuroscience publication_status: published publisher: Academic Press publist_id: '5553' pubrep_id: '979' quality_controlled: '1' status: public title: Modeling Alzheimer's disease with human induced pluripotent stem (iPS) cells tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 73 year: '2016' ... --- _id: '1253' abstract: - lang: eng text: This article provides an introduction to the role of microRNAs in the nervous system and outlines their potential involvement in the pathophysiology of schizophrenia, which is hypothesized to arise owing to environmental factors and genetic predisposition. article_processing_charge: No author: - first_name: Lihuei full_name: Tsai, Lihuei last_name: Tsai - first_name: Sandra full_name: Siegert, Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 citation: ama: Tsai L, Siegert S. How MicroRNAs Are involved in splitting the mind. JAMA Psychiatry. 2016;73(4):409-410. doi:10.1001/jamapsychiatry.2015.3144 apa: Tsai, L., & Siegert, S. (2016). How MicroRNAs Are involved in splitting the mind. JAMA Psychiatry. American Medical Association. https://doi.org/10.1001/jamapsychiatry.2015.3144 chicago: Tsai, Lihuei, and Sandra Siegert. “How MicroRNAs Are Involved in Splitting the Mind.” JAMA Psychiatry. American Medical Association, 2016. https://doi.org/10.1001/jamapsychiatry.2015.3144. ieee: L. Tsai and S. Siegert, “How MicroRNAs Are involved in splitting the mind,” JAMA Psychiatry, vol. 73, no. 4. American Medical Association, pp. 409–410, 2016. ista: Tsai L, Siegert S. 2016. How MicroRNAs Are involved in splitting the mind. JAMA Psychiatry. 73(4), 409–410. mla: Tsai, Lihuei, and Sandra Siegert. “How MicroRNAs Are Involved in Splitting the Mind.” JAMA Psychiatry, vol. 73, no. 4, American Medical Association, 2016, pp. 409–10, doi:10.1001/jamapsychiatry.2015.3144. short: L. Tsai, S. Siegert, JAMA Psychiatry 73 (2016) 409–410. date_created: 2018-12-11T11:50:58Z date_published: 2016-04-01T00:00:00Z date_updated: 2024-02-14T12:07:22Z day: '01' ddc: - '576' - '610' department: - _id: SaSi doi: 10.1001/jamapsychiatry.2015.3144 external_id: pmid: - '26963490' file: - access_level: open_access checksum: 649aee381f30f7ef7e9efa912d41c2e3 content_type: application/pdf creator: system date_created: 2018-12-12T10:17:24Z date_updated: 2020-07-14T12:44:41Z file_id: '5278' file_name: IST-2018-981-v1+1_YNP150011_annotatedproof_FINAL.pdf file_size: 601679 relation: main_file file_date_updated: 2020-07-14T12:44:41Z has_accepted_license: '1' intvolume: ' 73' issue: '4' language: - iso: eng month: '04' oa: 1 oa_version: Submitted Version page: 409 - 410 pmid: 1 publication: JAMA Psychiatry publication_identifier: issn: - 2168-622X publication_status: published publisher: American Medical Association publist_id: '6074' pubrep_id: '981' quality_controlled: '1' scopus_import: '1' status: public title: How MicroRNAs Are involved in splitting the mind type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 73 year: '2016' ... --- _id: '1803' abstract: - lang: eng text: Repeated stress has been suggested to underlie learning and memory deficits via the basolateral amygdala (BLA) and the hippocampus; however, the functional contribution of BLA inputs to the hippocampus and their molecular repercussions are not well understood. Here we show that repeated stress is accompanied by generation of the Cdk5 (cyclin-dependent kinase 5)-activator p25, up-regulation and phosphorylation of glucocorticoid receptors, increased HDAC2 expression, and reduced expression of memoryrelated genes in the hippocampus. A combination of optogenetic and pharmacosynthetic approaches shows that BLA activation is both necessary and sufficient for stress-associated molecular changes and memory impairments. Furthermore, we show that this effect relies on direct glutamatergic projections from the BLA to the dorsal hippocampus. Finally, we show that p25 generation is necessary for the stress-induced memory dysfunction. Taken together, our data provide a neural circuit model for stress-induced hippocampal memory deficits through BLA activity-dependent p25 generation. acknowledgement: |- AG047661; NIH; Schweizerische Nationalfonds zur Förderung der Wissenschaftlichen Forschung NS051874; NIH; Schweizerische Nationalfonds zur Förderung der Wissenschaftlichen Forschung SNSF; Schweizerische Nationalfonds zur Förderung der Wissenschaftlichen Forschung author: - first_name: Damien full_name: Rei, Damien last_name: Rei - first_name: Xenos full_name: Mason, Xenos last_name: Mason - first_name: Jinsoo full_name: Seo, Jinsoo last_name: Seo - first_name: Johannes full_name: Gräff, Johannes last_name: Gräff - first_name: Andrii full_name: Rudenko, Andrii last_name: Rudenko - first_name: Jùn full_name: Wang, Jùn last_name: Wang - first_name: Richard full_name: Rueda, Richard last_name: Rueda - first_name: Sandra full_name: Sandra Siegert id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 - first_name: Sukhee full_name: Cho, Sukhee last_name: Cho - first_name: Rebecca full_name: Canter, Rebecca G last_name: Canter - first_name: Alison full_name: Mungenast, Alison E last_name: Mungenast - first_name: Karl full_name: Deisseroth, Karl A last_name: Deisseroth - first_name: Lihuei full_name: Tsai, Lihuei last_name: Tsai citation: ama: Rei D, Mason X, Seo J, et al. Basolateral amygdala bidirectionally modulates stress induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway. PNAS. 2015;112(23):7291-7296. doi:10.1073/pnas.1415845112 apa: Rei, D., Mason, X., Seo, J., Gräff, J., Rudenko, A., Wang, J., … Tsai, L. (2015). Basolateral amygdala bidirectionally modulates stress induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.1415845112 chicago: Rei, Damien, Xenos Mason, Jinsoo Seo, Johannes Gräff, Andrii Rudenko, Jùn Wang, Richard Rueda, et al. “Basolateral Amygdala Bidirectionally Modulates Stress Induced Hippocampal Learning and Memory Deficits through a P25/Cdk5-Dependent Pathway.” PNAS. National Academy of Sciences, 2015. https://doi.org/10.1073/pnas.1415845112. ieee: D. Rei et al., “Basolateral amygdala bidirectionally modulates stress induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway,” PNAS, vol. 112, no. 23. National Academy of Sciences, pp. 7291–7296, 2015. ista: Rei D, Mason X, Seo J, Gräff J, Rudenko A, Wang J, Rueda R, Siegert S, Cho S, Canter R, Mungenast A, Deisseroth K, Tsai L. 2015. Basolateral amygdala bidirectionally modulates stress induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway. PNAS. 112(23), 7291–7296. mla: Rei, Damien, et al. “Basolateral Amygdala Bidirectionally Modulates Stress Induced Hippocampal Learning and Memory Deficits through a P25/Cdk5-Dependent Pathway.” PNAS, vol. 112, no. 23, National Academy of Sciences, 2015, pp. 7291–96, doi:10.1073/pnas.1415845112. short: D. Rei, X. Mason, J. Seo, J. Gräff, A. Rudenko, J. Wang, R. Rueda, S. Siegert, S. Cho, R. Canter, A. Mungenast, K. Deisseroth, L. Tsai, PNAS 112 (2015) 7291–7296. date_created: 2018-12-11T11:54:06Z date_published: 2015-06-09T00:00:00Z date_updated: 2021-01-12T06:53:18Z day: '09' doi: 10.1073/pnas.1415845112 extern: 1 intvolume: ' 112' issue: '23' month: '06' page: 7291 - 7296 publication: PNAS publication_status: published publisher: National Academy of Sciences publist_id: '5307' quality_controlled: 0 status: public title: Basolateral amygdala bidirectionally modulates stress induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway type: journal_article volume: 112 year: '2015' ... --- _id: '1802' abstract: - lang: eng text: Noncoding variants in the human MIR137 gene locus increase schizophrenia risk with genome-wide significance. However, the functional consequence of these risk alleles is unknown. Here we examined induced human neurons harboring the minor alleles of four disease-associated single nucleotide polymorphisms in MIR137. We observed increased MIR137 levels compared to those in major allele–carrying cells. microRNA-137 gain of function caused downregulation of the presynaptic target genes complexin-1 (Cplx1), Nsf and synaptotagmin-1 (Syt1), leading to impaired vesicle release. In vivo, miR-137 gain of function resulted in changes in synaptic vesicle pool distribution, impaired induction of mossy fiber long-term potentiation and deficits in hippocampus-dependent learning and memory. By sequestering endogenous miR-137, we were able to ameliorate the synaptic phenotypes. Moreover, reinstatement of Syt1 expression partially restored synaptic plasticity, demonstrating the importance of Syt1 as a miR-137 target. Our data provide new insight into the mechanism by which miR-137 dysregulation can impair synaptic plasticity in the hippocampus. acknowledgement: S.S. was supported by a Human Frontier Science Program (HFSP) long-term postdoctoral fellowship and a Swiss National Science Foundation fellowship for prospective researchers. E.J.K. was supported by a Simons Foundation Postdoctoral Fellowship. A.R. was supported by a NARSAD Young Investigator Award. This work was supported by a Seed Grant from the Simons Center for the Social Brain and US National Institutes of Health grant RO1 MH 091115 to L.-H.T. author: - first_name: Sandra full_name: Sandra Siegert id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 - first_name: Jinsoo full_name: Seo, Jinsoo last_name: Seo - first_name: Ester full_name: Kwon, Ester J last_name: Kwon - first_name: Andrii full_name: Rudenko, Andrii last_name: Rudenko - first_name: Sukhee full_name: Cho, Sukhee last_name: Cho - first_name: Wenyuan full_name: Wang, Wenyuan last_name: Wang - first_name: Zachary full_name: Flood, Zachary C last_name: Flood - first_name: Anthony full_name: Martorell, Anthony J last_name: Martorell - first_name: Maria full_name: Ericsson, Maria last_name: Ericsson - first_name: Alison full_name: Mungenast, Alison E last_name: Mungenast - first_name: Lihuei full_name: Tsai, Lihuei last_name: Tsai citation: ama: Siegert S, Seo J, Kwon E, et al. The schizophrenia risk gene product miR-137 alters presynaptic plasticity. Nature Neuroscience. 2015;18:1008-1016. doi:10.1038/nn.4023 apa: Siegert, S., Seo, J., Kwon, E., Rudenko, A., Cho, S., Wang, W., … Tsai, L. (2015). The schizophrenia risk gene product miR-137 alters presynaptic plasticity. Nature Neuroscience. Nature Publishing Group. https://doi.org/10.1038/nn.4023 chicago: Siegert, Sandra, Jinsoo Seo, Ester Kwon, Andrii Rudenko, Sukhee Cho, Wenyuan Wang, Zachary Flood, et al. “The Schizophrenia Risk Gene Product MiR-137 Alters Presynaptic Plasticity.” Nature Neuroscience. Nature Publishing Group, 2015. https://doi.org/10.1038/nn.4023. ieee: S. Siegert et al., “The schizophrenia risk gene product miR-137 alters presynaptic plasticity,” Nature Neuroscience, vol. 18. Nature Publishing Group, pp. 1008–1016, 2015. ista: Siegert S, Seo J, Kwon E, Rudenko A, Cho S, Wang W, Flood Z, Martorell A, Ericsson M, Mungenast A, Tsai L. 2015. The schizophrenia risk gene product miR-137 alters presynaptic plasticity. Nature Neuroscience. 18, 1008–1016. mla: Siegert, Sandra, et al. “The Schizophrenia Risk Gene Product MiR-137 Alters Presynaptic Plasticity.” Nature Neuroscience, vol. 18, Nature Publishing Group, 2015, pp. 1008–16, doi:10.1038/nn.4023. short: S. Siegert, J. Seo, E. Kwon, A. Rudenko, S. Cho, W. Wang, Z. Flood, A. Martorell, M. Ericsson, A. Mungenast, L. Tsai, Nature Neuroscience 18 (2015) 1008–1016. date_created: 2018-12-11T11:54:05Z date_published: 2015-07-01T00:00:00Z date_updated: 2021-01-12T06:53:18Z day: '01' doi: 10.1038/nn.4023 extern: 1 intvolume: ' 18' month: '07' page: 1008 - 1016 publication: Nature Neuroscience publication_status: published publisher: Nature Publishing Group publist_id: '5308' quality_controlled: 0 status: public title: The schizophrenia risk gene product miR-137 alters presynaptic plasticity type: journal_article volume: 18 year: '2015' ... --- _id: '1801' abstract: - lang: eng text: Brain circuits are assembled from a large variety of morphologically and functionally diverse cell types. It is not known how the intermingled cell types of an individual adult brain region differ in their expressed genomes. Here we describe an atlas of cell type transcriptomes in one brain region, the mouse retina. We found that each adult cell type expressed a specific set of genes, including a unique set of transcription factors, forming a 'barcode' for cell identity. Cell type transcriptomes carried enough information to categorize cells into morphological classes and types. Several genes that were specifically expressed in particular retinal circuit elements, such as inhibitory neuron types, are associated with eye diseases. The resource described here allows gene expression to be compared across adult retinal cell types, experimenting with specific transcription factors to differentiate stem or somatic cells to retinal cell types, and predicting cellular targets of newly discovered disease-associated genes. acknowledgement: The study was supported by Friedrich Miescher Institute funds, Alcon award, a National Center of Competence in Research Genetics grant, a European Research Council grant, a Swiss-Hungarian grant, and RETICIRC, TREATRUSH, SEEBETTER and OPTONEURO grants from the European Union to B.R. author: - first_name: Sandra full_name: Sandra Siegert id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 - first_name: Erik full_name: Cabuy, Erik last_name: Cabuy - first_name: Brigitte full_name: Scherf, Brigitte G last_name: Scherf - first_name: Hubertus full_name: Kohler, Hubertus last_name: Kohler - first_name: Satchidananda full_name: Panda, Satchidananda last_name: Panda - first_name: Yunzheng full_name: Le, Yunzheng last_name: Le - first_name: Hans full_name: Fehling, Hans J last_name: Fehling - first_name: Dimos full_name: Gaidatzis, Dimos last_name: Gaidatzis - first_name: Michael full_name: Stadler, Michael B last_name: Stadler - first_name: Botond full_name: Roska, Botond M last_name: Roska citation: ama: Siegert S, Cabuy E, Scherf B, et al. Transcriptional code and disease map for adult retinal cell types. Nature Neuroscience. 2012;15(3):487-495. doi:10.1038/nn.3032 apa: Siegert, S., Cabuy, E., Scherf, B., Kohler, H., Panda, S., Le, Y., … Roska, B. (2012). Transcriptional code and disease map for adult retinal cell types. Nature Neuroscience. Nature Publishing Group. https://doi.org/10.1038/nn.3032 chicago: Siegert, Sandra, Erik Cabuy, Brigitte Scherf, Hubertus Kohler, Satchidananda Panda, Yunzheng Le, Hans Fehling, Dimos Gaidatzis, Michael Stadler, and Botond Roska. “Transcriptional Code and Disease Map for Adult Retinal Cell Types.” Nature Neuroscience. Nature Publishing Group, 2012. https://doi.org/10.1038/nn.3032. ieee: S. Siegert et al., “Transcriptional code and disease map for adult retinal cell types,” Nature Neuroscience, vol. 15, no. 3. Nature Publishing Group, pp. 487–495, 2012. ista: Siegert S, Cabuy E, Scherf B, Kohler H, Panda S, Le Y, Fehling H, Gaidatzis D, Stadler M, Roska B. 2012. Transcriptional code and disease map for adult retinal cell types. Nature Neuroscience. 15(3), 487–495. mla: Siegert, Sandra, et al. “Transcriptional Code and Disease Map for Adult Retinal Cell Types.” Nature Neuroscience, vol. 15, no. 3, Nature Publishing Group, 2012, pp. 487–95, doi:10.1038/nn.3032. short: S. Siegert, E. Cabuy, B. Scherf, H. Kohler, S. Panda, Y. Le, H. Fehling, D. Gaidatzis, M. Stadler, B. Roska, Nature Neuroscience 15 (2012) 487–495. date_created: 2018-12-11T11:54:05Z date_published: 2012-03-01T00:00:00Z date_updated: 2021-01-12T06:53:17Z day: '01' doi: 10.1038/nn.3032 extern: 1 intvolume: ' 15' issue: '3' month: '03' page: 487 - 495 publication: Nature Neuroscience publication_status: published publisher: Nature Publishing Group publist_id: '5309' quality_controlled: 0 status: public title: Transcriptional code and disease map for adult retinal cell types type: journal_article volume: 15 year: '2012' ... --- _id: '1800' abstract: - lang: eng text: Retinitis pigmentosa refers to a diverse group of hereditary diseases that lead to incurable blindness, affecting two million people worldwide. As a common pathology, rod photoreceptors die early, whereas light-insensitive, morphologically altered cone photoreceptors persist longer. It is unknown if these cones are accessible for therapeutic intervention. Here, we show that expression of archaebacterial halorhodopsin in light-insensitive cones can substitute for the native phototransduction cascade and restore light sensitivity in mouse models of retinitis pigmentosa. Resensitized photoreceptors activate all retinal cone pathways, drive sophisticated retinal circuit functions (including directional selectivity), activate cortical circuits, and mediate visually guided behaviors. Using human ex vivo retinas, we show that halorhodopsin can reactivate light-insensitive human photoreceptors. Finally, we identified blind patients with persisting, light-insensitive cones for potential halorhodopsin-based therapy. acknowledgement: This study was supported by Friedrich Miescher Institute funds; a U.S. Office of Naval Research Naval International Cooperative Opportunities in Science and Technology Program grant; a Marie Curie Excellence grant and a European Union (EU) HEALTH-F2-223156 grant to B.R.; a grant from the EU (RETICIRC) to B.R. and S.P.; grants from the Agence nationale de la recherche (MEDINAS, RETINE) to S.P.; a Center Grant from Foundation Fighting Blindness (U.S.) to S.M.-S. and J.A.S.; grants from the Swiss National Science Foundation and the EU to D.T.; a grant from the EU (TREATRUSH) to J.A.S., S.P., and B.R.; a Marie Curie Postdoctoral Fellowship to D.B.; and a National Centers of Competence in Research Frontiers in Genetics fellowship to V.B. and A.C.G. The Ocular Genetics Unit at Trinity College Dublin is supported by Science Foundation Ireland author: - first_name: Volker full_name: Busskamp, Volker last_name: Busskamp - first_name: Jens full_name: Duebel, Jens last_name: Duebel - first_name: Dávid full_name: Bálya, Dávid last_name: Bálya - first_name: Mathias full_name: Fradot, Mathias last_name: Fradot - first_name: Tim full_name: Viney, Tim J last_name: Viney - first_name: Sandra full_name: Sandra Siegert id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 - first_name: Anna full_name: Groner, Anna C last_name: Groner - first_name: Erik full_name: Cabuy, Erik last_name: Cabuy - first_name: Valérie full_name: Forster, Valérie last_name: Forster - first_name: Mathias full_name: Seeliger, Mathias W last_name: Seeliger - first_name: Martin full_name: Biel, Martin last_name: Biel - first_name: Peter full_name: Humphries, Peter last_name: Humphries - first_name: Michel full_name: Pâques, Michel last_name: Pâques - first_name: Saddek full_name: Mohand-Saïd, Saddek last_name: Mohand Saïd - first_name: Didier full_name: Trono, Didier last_name: Trono - first_name: Karl full_name: Deisseroth, Karl A last_name: Deisseroth - first_name: José full_name: Sähel, José A last_name: Sähel - first_name: Serge full_name: Picaud, Serge A last_name: Picaud - first_name: Botond full_name: Roska, Botond M last_name: Roska citation: ama: Busskamp V, Duebel J, Bálya D, et al. Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa. Science. 2010;329(5990):413-417. doi:10.1126/science.1190897 apa: Busskamp, V., Duebel, J., Bálya, D., Fradot, M., Viney, T., Siegert, S., … Roska, B. (2010). Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.1190897 chicago: Busskamp, Volker, Jens Duebel, Dávid Bálya, Mathias Fradot, Tim Viney, Sandra Siegert, Anna Groner, et al. “Genetic Reactivation of Cone Photoreceptors Restores Visual Responses in Retinitis Pigmentosa.” Science. American Association for the Advancement of Science, 2010. https://doi.org/10.1126/science.1190897. ieee: V. Busskamp et al., “Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa,” Science, vol. 329, no. 5990. American Association for the Advancement of Science, pp. 413–417, 2010. ista: Busskamp V, Duebel J, Bálya D, Fradot M, Viney T, Siegert S, Groner A, Cabuy E, Forster V, Seeliger M, Biel M, Humphries P, Pâques M, Mohand Saïd S, Trono D, Deisseroth K, Sähel J, Picaud S, Roska B. 2010. Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa. Science. 329(5990), 413–417. mla: Busskamp, Volker, et al. “Genetic Reactivation of Cone Photoreceptors Restores Visual Responses in Retinitis Pigmentosa.” Science, vol. 329, no. 5990, American Association for the Advancement of Science, 2010, pp. 413–17, doi:10.1126/science.1190897. short: V. Busskamp, J. Duebel, D. Bálya, M. Fradot, T. Viney, S. Siegert, A. Groner, E. Cabuy, V. Forster, M. Seeliger, M. Biel, P. Humphries, M. Pâques, S. Mohand Saïd, D. Trono, K. Deisseroth, J. Sähel, S. Picaud, B. Roska, Science 329 (2010) 413–417. date_created: 2018-12-11T11:54:05Z date_published: 2010-07-23T00:00:00Z date_updated: 2021-01-12T06:53:17Z day: '23' doi: 10.1126/science.1190897 extern: 1 intvolume: ' 329' issue: '5990' month: '07' page: 413 - 417 publication: Science publication_status: published publisher: American Association for the Advancement of Science publist_id: '5310' quality_controlled: 0 status: public title: Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa type: journal_article volume: 329 year: '2010' ... --- _id: '1799' abstract: - lang: eng text: 'The detection of approaching objects, such as looming predators, is necessary for survival. Which neurons and circuits mediate this function? We combined genetic labeling of cell types, two-photon microscopy, electrophysiology and theoretical modeling to address this question. We identify an approach-sensitive ganglion cell type in the mouse retina, resolve elements of its afferent neural circuit, and describe how these confer approach sensitivity on the ganglion cell. The circuit''s essential building block is a rapid inhibitory pathway: it selectively suppresses responses to non-approaching objects. This rapid inhibitory pathway, which includes AII amacrine cells connected to bipolar cells through electrical synapses, was previously described in the context of night-time vision. In the daytime conditions of our experiments, the same pathway conveys signals in the reverse direction. The dual use of a neural pathway in different physiological conditions illustrates the efficiency with which several functions can be accommodated in a single circuit.' acknowledgement: The study was supported by Friedrich Miescher Institute funds, a US Office of Naval Research Naval International Cooperative Opportunities in Science and Technology program grant, a Marie Curie Excellence Grant, a Human Frontier Science Program Young Investigator grant, a National Centers of Competence in Research in Genetics grant and a European Union HEALTH-F2-223156 grant to B.R., a Marie Curie Postdoctoral Fellowship to T.A.M., the Centre National de la Recherche Scientifique through the Unité Mixte de Recherche 8550 to R.A.d.S. author: - first_name: Thomas full_name: Münch, Thomas A last_name: Münch - first_name: Ravá full_name: Da Silveira, Ravá A last_name: Da Silveira - first_name: Sandra full_name: Sandra Siegert id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 - first_name: Tim full_name: Viney, Tim J last_name: Viney - first_name: Gautam full_name: Awatramani, Gautam B last_name: Awatramani - first_name: Botond full_name: Roska, Botond M last_name: Roska citation: ama: Münch T, Da Silveira R, Siegert S, Viney T, Awatramani G, Roska B. Approach sensitivity in the retina processed by a multifunctional neural circuit. Nature Neuroscience. 2009;12(10):1308-1316. doi:10.1038/nn.2389 apa: Münch, T., Da Silveira, R., Siegert, S., Viney, T., Awatramani, G., & Roska, B. (2009). Approach sensitivity in the retina processed by a multifunctional neural circuit. Nature Neuroscience. Nature Publishing Group. https://doi.org/10.1038/nn.2389 chicago: Münch, Thomas, Ravá Da Silveira, Sandra Siegert, Tim Viney, Gautam Awatramani, and Botond Roska. “Approach Sensitivity in the Retina Processed by a Multifunctional Neural Circuit.” Nature Neuroscience. Nature Publishing Group, 2009. https://doi.org/10.1038/nn.2389. ieee: T. Münch, R. Da Silveira, S. Siegert, T. Viney, G. Awatramani, and B. Roska, “Approach sensitivity in the retina processed by a multifunctional neural circuit,” Nature Neuroscience, vol. 12, no. 10. Nature Publishing Group, pp. 1308–1316, 2009. ista: Münch T, Da Silveira R, Siegert S, Viney T, Awatramani G, Roska B. 2009. Approach sensitivity in the retina processed by a multifunctional neural circuit. Nature Neuroscience. 12(10), 1308–1316. mla: Münch, Thomas, et al. “Approach Sensitivity in the Retina Processed by a Multifunctional Neural Circuit.” Nature Neuroscience, vol. 12, no. 10, Nature Publishing Group, 2009, pp. 1308–16, doi:10.1038/nn.2389. short: T. Münch, R. Da Silveira, S. Siegert, T. Viney, G. Awatramani, B. Roska, Nature Neuroscience 12 (2009) 1308–1316. date_created: 2018-12-11T11:54:04Z date_published: 2009-10-01T00:00:00Z date_updated: 2021-01-12T06:53:16Z day: '01' doi: 10.1038/nn.2389 extern: 1 intvolume: ' 12' issue: '10' month: '10' page: 1308 - 1316 publication: Nature Neuroscience publication_status: published publisher: Nature Publishing Group publist_id: '5311' quality_controlled: 0 status: public title: Approach sensitivity in the retina processed by a multifunctional neural circuit type: journal_article volume: 12 year: '2009' ... --- _id: '1798' abstract: - lang: eng text: The mammalian brain is assembled from thousands of neuronal cell types that are organized in distinct circuits to perform behaviorally relevant computations. Transgenic mouse lines with selectively marked cell types would facilitate our ability to dissect functional components of complex circuits. We carried out a screen for cell type-specific green fluorescent protein expression in the retina using BAC transgenic mice from the GENSAT project. Among others, we identified mouse lines in which the inhibitory cell types of the night vision and directional selective circuit were selectively labeled. We quantified the stratification patterns to predict potential synaptic connectivity between marked cells of different lines and found that some of the lines enabled targeted recordings and imaging of cell types from developing or mature retinal circuits. Our results suggest the potential use of a stratification-based screening approach for characterizing neuronal circuitry in other layered brain structures, such as the neocortex. acknowledgement: This study was supported by Friedrich Miescher Institute funds, a US Office of Naval Research Naval International Cooperative Opportunities in Science and Technology Program grant, a Marie Curie Excellence grant, a National Center for Competence in Research in Genetics grant and a European Union HEALTH-F2-223156 grant to B.R., and by National Institute of Neurological Disorders and Stroke contracts N01NS02331 and HHSN271200723701C to N.H. author: - first_name: Sandra full_name: Sandra Siegert id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 - first_name: Brigitte full_name: Scherf, Brigitte G last_name: Scherf - first_name: Karina full_name: Del Punta, Karina last_name: Del Punta - first_name: Nick full_name: Didkovsky, Nick last_name: Didkovsky - first_name: Nathaniel full_name: Heintz, Nathaniel M last_name: Heintz - first_name: Botond full_name: Roska, Botond M last_name: Roska citation: ama: Siegert S, Scherf B, Del Punta K, Didkovsky N, Heintz N, Roska B. Genetic address book for retinal cell types. Nature Neuroscience. 2009;12(9):1197-1204. doi:10.1038/nn.2370 apa: Siegert, S., Scherf, B., Del Punta, K., Didkovsky, N., Heintz, N., & Roska, B. (2009). Genetic address book for retinal cell types. Nature Neuroscience. Nature Publishing Group. https://doi.org/10.1038/nn.2370 chicago: Siegert, Sandra, Brigitte Scherf, Karina Del Punta, Nick Didkovsky, Nathaniel Heintz, and Botond Roska. “Genetic Address Book for Retinal Cell Types.” Nature Neuroscience. Nature Publishing Group, 2009. https://doi.org/10.1038/nn.2370. ieee: S. Siegert, B. Scherf, K. Del Punta, N. Didkovsky, N. Heintz, and B. Roska, “Genetic address book for retinal cell types,” Nature Neuroscience, vol. 12, no. 9. Nature Publishing Group, pp. 1197–1204, 2009. ista: Siegert S, Scherf B, Del Punta K, Didkovsky N, Heintz N, Roska B. 2009. Genetic address book for retinal cell types. Nature Neuroscience. 12(9), 1197–1204. mla: Siegert, Sandra, et al. “Genetic Address Book for Retinal Cell Types.” Nature Neuroscience, vol. 12, no. 9, Nature Publishing Group, 2009, pp. 1197–204, doi:10.1038/nn.2370. short: S. Siegert, B. Scherf, K. Del Punta, N. Didkovsky, N. Heintz, B. Roska, Nature Neuroscience 12 (2009) 1197–1204. date_created: 2018-12-11T11:54:04Z date_published: 2009-09-01T00:00:00Z date_updated: 2021-01-12T06:53:16Z day: '01' doi: 10.1038/nn.2370 extern: 1 intvolume: ' 12' issue: '9' month: '09' page: 1197 - 1204 publication: Nature Neuroscience publication_status: published publisher: Nature Publishing Group publist_id: '5312' quality_controlled: 0 status: public title: Genetic address book for retinal cell types type: journal_article volume: 12 year: '2009' ... --- _id: '1797' abstract: - lang: eng text: Intrinsically photosensitive melanopsin-containing retinal ganglion cells (ipRGCs) control important physiological processes, including the circadian rhythm, the pupillary reflex, and the suppression of locomotor behavior (reviewed in [1]). ipRGCs are also activated by classical photoreceptors, the rods and cones, through local retinal circuits [2, 3]. ipRGCs can be transsynaptically labeled through the pupillary-reflex circuit with the derivatives of the Bartha strain of the alphaherpesvirus pseudorabies virus(PRV) [4, 5] that express GFP [6-12]. Bartha-strain derivatives spread only in the retrograde direction [13]. There is evidence that infected cells function normally for a while during GFP expression [7]. Here we combine transsynaptic PRV labeling, two-photon laser microscopy, and electrophysiological techniques to trace the local circuit of different ipRGC subtypes in the mouse retina and record light-evoked activity from the transsynaptically labeled ganglion cells. First, we show that ipRGCs are connected by monostratified amacrine cells that provide strong inhibition from classical-photoreceptor-driven circuits. Second, we show evidence that dopaminergic interplexiform cells are synaptically connected to ipRGCs. The latter finding provides a circuitry link between light-dark adaptation and ipRGC function. acknowledgement: This study was supported by Office of Naval Research Multidisciplinary University Research Initiative [ONR MURI] and Naval International Cooperative Opportunities in Science and Technology Program [NICOP] grants, a Marie Curie Excellence Grant, a Human Frontier Science Program [HFSP] Young Investigator grant, and Friedrich Miescher Institute funds to B.R. author: - first_name: Tim full_name: Viney, Tim J last_name: Viney - first_name: Kamill full_name: Bálint, Kamill last_name: Bálint - first_name: Dániel full_name: Hillier, Dániel last_name: Hillier - first_name: Sandra full_name: Sandra Siegert id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 - first_name: Zsolt full_name: Boldogköi, Zsolt S last_name: Boldogköi - first_name: Lynn full_name: Enquist, Lynn W last_name: Enquist - first_name: Markus full_name: Meister, Markus last_name: Meister - first_name: Constance full_name: Cepko, Constance L last_name: Cepko - first_name: Botond full_name: Roska, Botond M last_name: Roska citation: ama: Viney T, Bálint K, Hillier D, et al. Local retinal circuits of melanopsin-containing ganglion cells identified by transsynaptic viral tracing. Current Biology. 2007;17(11):981-988. doi:10.1016/j.cub.2007.04.058 apa: Viney, T., Bálint, K., Hillier, D., Siegert, S., Boldogköi, Z., Enquist, L., … Roska, B. (2007). Local retinal circuits of melanopsin-containing ganglion cells identified by transsynaptic viral tracing. Current Biology. Cell Press. https://doi.org/10.1016/j.cub.2007.04.058 chicago: Viney, Tim, Kamill Bálint, Dániel Hillier, Sandra Siegert, Zsolt Boldogköi, Lynn Enquist, Markus Meister, Constance Cepko, and Botond Roska. “Local Retinal Circuits of Melanopsin-Containing Ganglion Cells Identified by Transsynaptic Viral Tracing.” Current Biology. Cell Press, 2007. https://doi.org/10.1016/j.cub.2007.04.058. ieee: T. Viney et al., “Local retinal circuits of melanopsin-containing ganglion cells identified by transsynaptic viral tracing,” Current Biology, vol. 17, no. 11. Cell Press, pp. 981–988, 2007. ista: Viney T, Bálint K, Hillier D, Siegert S, Boldogköi Z, Enquist L, Meister M, Cepko C, Roska B. 2007. Local retinal circuits of melanopsin-containing ganglion cells identified by transsynaptic viral tracing. Current Biology. 17(11), 981–988. mla: Viney, Tim, et al. “Local Retinal Circuits of Melanopsin-Containing Ganglion Cells Identified by Transsynaptic Viral Tracing.” Current Biology, vol. 17, no. 11, Cell Press, 2007, pp. 981–88, doi:10.1016/j.cub.2007.04.058. short: T. Viney, K. Bálint, D. Hillier, S. Siegert, Z. Boldogköi, L. Enquist, M. Meister, C. Cepko, B. Roska, Current Biology 17 (2007) 981–988. date_created: 2018-12-11T11:54:04Z date_published: 2007-06-05T00:00:00Z date_updated: 2021-01-12T06:53:15Z day: '05' doi: 10.1016/j.cub.2007.04.058 extern: 1 intvolume: ' 17' issue: '11' month: '06' page: 981 - 988 publication: Current Biology publication_status: published publisher: Cell Press publist_id: '5313' quality_controlled: 0 status: public title: Local retinal circuits of melanopsin-containing ganglion cells identified by transsynaptic viral tracing type: journal_article volume: 17 year: '2007' ...