--- OA_place: publisher _id: '19557' acknowledged_ssus: - _id: Bio - _id: PreCl - _id: ScienComp acknowledgement: "The work presented in this doctoral thesis was performed at the Institute of Science\r\nand Technology (ISTA) and financially supported by a European Research Council\r\n(ERC) Consolidator Grant (PR1028ERC02), by SFARI (PR1028SIM02) and by the\r\nAustrian Science Fund (FWF) to Gaia Novarino (PE1028W1232). I am very thankful\r\nto the Doctoral Program “Molecular Drug Targets” (MolTag) for offering me financial\r\nsupport to perform essential experiments during my PhD studies and to participate in\r\ninternational conferences and courses." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Lena A full_name: Schwarz, Lena A id: 29A8453C-F248-11E8-B48F-1D18A9856A87 last_name: Schwarz citation: ama: Schwarz LA. Mapping developmental dynamics of autism spectrum disorder mouse models at single-cell resolution. 2025. doi:10.15479/AT-ISTA-19557 apa: Schwarz, L. A. (2025). Mapping developmental dynamics of autism spectrum disorder mouse models at single-cell resolution. Institute of Science and Technology Austria. https://doi.org/10.15479/AT-ISTA-19557 chicago: Schwarz, Lena A. “Mapping Developmental Dynamics of Autism Spectrum Disorder Mouse Models at Single-Cell Resolution.” Institute of Science and Technology Austria, 2025. https://doi.org/10.15479/AT-ISTA-19557. ieee: L. A. Schwarz, “Mapping developmental dynamics of autism spectrum disorder mouse models at single-cell resolution,” Institute of Science and Technology Austria, 2025. ista: Schwarz LA. 2025. Mapping developmental dynamics of autism spectrum disorder mouse models at single-cell resolution. Institute of Science and Technology Austria. mla: Schwarz, Lena A. Mapping Developmental Dynamics of Autism Spectrum Disorder Mouse Models at Single-Cell Resolution. Institute of Science and Technology Austria, 2025, doi:10.15479/AT-ISTA-19557. short: L.A. Schwarz, Mapping Developmental Dynamics of Autism Spectrum Disorder Mouse Models at Single-Cell Resolution, Institute of Science and Technology Austria, 2025. corr_author: '1' date_created: 2025-04-14T06:59:06Z date_published: 2025-04-14T00:00:00Z date_updated: 2026-04-14T09:07:14Z day: '14' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: GaNo doi: 10.15479/AT-ISTA-19557 file: - access_level: closed checksum: 50290a8604edb0a720387f01e9d59fe4 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: lschwarz date_created: 2025-04-15T08:43:36Z date_updated: 2025-04-15T08:43:36Z file_id: '19561' file_name: Schwarz_Thesis_2025_FINAL.docx file_size: 21783427 relation: source_file - access_level: closed checksum: ed028488180ac4901e018ef1c330cf01 content_type: application/pdf creator: lschwarz date_created: 2025-04-15T08:43:42Z date_updated: 2026-03-27T13:15:08Z embargo: 2026-10-15 embargo_to: open_access file_id: '19562' file_name: Schwarz_Thesis_2025_FINALpdfa.pdf file_size: 11432175 relation: main_file file_date_updated: 2026-03-27T13:15:08Z has_accepted_license: '1' language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '04' oa_version: Published Version page: '124' project: - _id: 9B91375C-BA93-11EA-9121-9846C619BF3A grant_number: '707964' name: Critical windows and reversibility of ASD associated with mutations in chromatin remodelers - _id: 34ba8964-11ca-11ed-8bc3-e15864e7e9a6 grant_number: '101044865' name: Toward an understanding of the brain interstitial system and the extracellular proteome in health and autism spectrum disorders - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232 name: Molecular Drug Targets publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '12802' relation: part_of_dissertation status: public - id: '9429' relation: part_of_dissertation status: public status: public supervisor: - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 title: Mapping developmental dynamics of autism spectrum disorder mouse models at single-cell resolution 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: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2025' ... --- OA_place: publisher OA_type: hybrid PlanS_conform: '1' _id: '19704' abstract: - lang: eng text: The information-processing capability of the brain’s cellular network depends on the physical wiring pattern between neurons and their molecular and functional characteristics. Mapping neurons and resolving their individual synaptic connections can be achieved by volumetric imaging at nanoscale resolution1,2 with dense cellular labelling. Light microscopy is uniquely positioned to visualize specific molecules, but dense, synapse-level circuit reconstruction by light microscopy has been out of reach, owing to limitations in resolution, contrast and volumetric imaging capability. Here we describe light-microscopy-based connectomics (LICONN). We integrated specifically engineered hydrogel embedding and expansion with comprehensive deep-learning-based segmentation and analysis of connectivity, thereby directly incorporating molecular information into synapse-level reconstructions of brain tissue. LICONN will allow synapse-level phenotyping of brain tissue in biological experiments in a readily adoptable manner. acknowledged_ssus: - _id: Bio - _id: LifeSc - _id: ScienComp - _id: PreCl - _id: M-Shop - _id: E-Lib acknowledgement: 'We thank S. Dorkenwald and P. Li for critical reading of the manuscript, S. Loomba for discussions and E. Miguel for support with data handling. We acknowledge support from ISTA’s scientific service units: Imaging and Optics, Lab Support, Scientific Computing, the preclinical facility, the Miba Machine Shop and the library. We acknowledge funding from the following sources: Austrian Science Fund (FWF) grant DK W1232 (J.G.D. and M.R.T.); Austrian Academy of Sciences DOC fellowship 26137 (M.R.T.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.); the European Union’s Horizon 2020 research and innovation programme and Marie Skłodowska-Curie Actions Fellowship 665385 (J.L.); and the European Union’s Horizon 2020 research and innovation programme and European Research Council (ERC) grant 101044865 ‘SecretAutism’ (G.N.).Open access funding provided by Institute of Science and Technology (IST Austria).' article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Mojtaba full_name: Tavakoli, Mojtaba id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87 last_name: Tavakoli orcid: 0000-0002-7667-6854 - first_name: Julia full_name: Lyudchik, Julia id: 46E28B80-F248-11E8-B48F-1D18A9856A87 last_name: Lyudchik - first_name: Michał full_name: Januszewski, Michał last_name: Januszewski - first_name: Vitali full_name: Vistunou, Vitali id: 7e146587-8972-11ed-ae7b-d7a32ea86a81 last_name: Vistunou - first_name: Nathalie full_name: Agudelo Duenas, Nathalie id: 40E7F008-F248-11E8-B48F-1D18A9856A87 last_name: Agudelo Duenas - first_name: Jakob full_name: Vorlaufer, Jakob id: 937696FA-C996-11E9-8C7C-CF13E6697425 last_name: Vorlaufer orcid: 0009-0000-7590-3501 - 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: Caroline full_name: Kreuzinger, Caroline id: 382077BA-F248-11E8-B48F-1D18A9856A87 last_name: Kreuzinger - first_name: Bárbara full_name: Oliveira, Bárbara id: 3B03AA1A-F248-11E8-B48F-1D18A9856A87 last_name: Oliveira - first_name: Alban full_name: Cenameri, Alban id: 9ac8f577-2357-11eb-997a-e566c5550886 last_name: Cenameri - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Viren full_name: Jain, Viren last_name: Jain - 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: Tavakoli M, Lyudchik J, Januszewski M, et al. Light-microscopy-based connectomic reconstruction of mammalian brain tissue. Nature. 2025;642:398-410. doi:10.1038/s41586-025-08985-1 apa: Tavakoli, M., Lyudchik, J., Januszewski, M., Vistunou, V., Agudelo Duenas, N., Vorlaufer, J., … Danzl, J. G. (2025). Light-microscopy-based connectomic reconstruction of mammalian brain tissue. Nature. Springer Nature. https://doi.org/10.1038/s41586-025-08985-1 chicago: Tavakoli, Mojtaba, Julia Lyudchik, Michał Januszewski, Vitali Vistunou, Nathalie Agudelo Duenas, Jakob Vorlaufer, Christoph M Sommer, et al. “Light-Microscopy-Based Connectomic Reconstruction of Mammalian Brain Tissue.” Nature. Springer Nature, 2025. https://doi.org/10.1038/s41586-025-08985-1. ieee: M. Tavakoli et al., “Light-microscopy-based connectomic reconstruction of mammalian brain tissue,” Nature, vol. 642. Springer Nature, pp. 398–410, 2025. ista: Tavakoli M, Lyudchik J, Januszewski M, Vistunou V, Agudelo Duenas N, Vorlaufer J, Sommer CM, Kreuzinger C, Oliveira B, Cenameri A, Novarino G, Jain V, Danzl JG. 2025. Light-microscopy-based connectomic reconstruction of mammalian brain tissue. Nature. 642, 398–410. mla: Tavakoli, Mojtaba, et al. “Light-Microscopy-Based Connectomic Reconstruction of Mammalian Brain Tissue.” Nature, vol. 642, Springer Nature, 2025, pp. 398–410, doi:10.1038/s41586-025-08985-1. short: M. Tavakoli, J. Lyudchik, M. Januszewski, V. Vistunou, N. Agudelo Duenas, J. Vorlaufer, C.M. Sommer, C. Kreuzinger, B. Oliveira, A. Cenameri, G. Novarino, V. Jain, J.G. Danzl, Nature 642 (2025) 398–410. corr_author: '1' date_created: 2025-05-18T22:02:51Z date_published: 2025-06-12T00:00:00Z date_updated: 2026-04-28T13:33:34Z day: '12' ddc: - '570' department: - _id: JoDa - _id: GradSch - _id: Bio - _id: GaNo doi: 10.1038/s41586-025-08985-1 ec_funded: 1 external_id: isi: - '001483477000001' pmid: - '40335689' file: - access_level: open_access checksum: ebc99d7108e728f46db0a009292675ef content_type: application/pdf creator: dernst date_created: 2025-07-03T06:55:20Z date_updated: 2025-07-03T06:55:20Z file_id: '19959' file_name: 2025_Nature_Tavakoli.pdf file_size: 133201290 relation: main_file success: 1 file_date_updated: 2025-07-03T06:55:20Z has_accepted_license: '1' intvolume: ' 642' isi: 1 language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: 398-410 pmid: 1 project: - _id: 6285a163-2b32-11ec-9570-8e204ca2dba5 grant_number: '26137' name: Studying Organelle Structure and Function at Nanoscale Resolution with Expansion Microscopy - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program - _id: 34ba8964-11ca-11ed-8bc3-e15864e7e9a6 grant_number: '101044865' name: Toward an understanding of the brain interstitial system and the extracellular proteome in health and autism spectrum disorders - _id: 26AA4EF2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets publication: Nature publication_identifier: eissn: - 1476-4687 issn: - 0028-0836 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/piecing-together-the-brain-puzzle/ record: - id: '18677' relation: earlier_version status: public - id: '18697' relation: research_data status: public scopus_import: '1' status: public title: Light-microscopy-based connectomic reconstruction of mammalian brain tissue 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: ba8df636-2132-11f1-aed0-ed93e2281fdd volume: 642 year: '2025' ... --- OA_place: repository _id: '18677' abstract: - lang: eng text: The information-processing capability of the brain’s cellular network depends on the physical wiring pattern between neurons and their molecular and functional characteristics. Mapping neurons and resolving their individual synaptic connections can be achieved by volumetric imaging at nanoscale resolution with dense cellular labeling. Light microscopy is uniquely positioned to visualize specific molecules but dense, synapse-level circuit reconstruction by light microscopy has been out of reach due to limitations in resolution, contrast, and volumetric imaging capability. Here we developed light-microscopy based connectomics (LICONN). We integrated specifically engineered hydrogel embedding and expansion with comprehensive deep-learning based segmentation and analysis of connectivity, thus directly incorporating molecular information in synapse-level brain tissue reconstructions. LICONN will allow synapse-level brain tissue phenotyping in biological experiments in a readily adoptable manner. acknowledged_ssus: - _id: E-Lib - _id: M-Shop - _id: LifeSc - _id: Bio - _id: ScienComp acknowledgement: "We thank Sven Dorkenwald and Peter Li for critical reading of the\r\nmanuscript. We acknowledge expert support by ISTA’s scientific service units: Imaging and\r\nOptics, Lab Support, Scientific Computing, Preclinical Facility, Miba Machine Shop, and Library.\r\nWe gratefully acknowledge funding by the following sources:\r\nAustrian Science Fund (FWF) grant DK W1232 (JGD, MRT)\r\nAustrian Academy of Sciences DOC fellowship 26137 (MRT)\r\nEU Horizon 2020 program, Marie Skłodowska-Curie Actions Fellowship 665385 (JL)\r\nGesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (JGD)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European Research\r\nCouncil (ERC) grant 101044865 “SecretAutism.”\r\n" article_processing_charge: No author: - first_name: Mojtaba full_name: Tavakoli, Mojtaba id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87 last_name: Tavakoli orcid: 0000-0002-7667-6854 - first_name: Julia full_name: Lyudchik, Julia id: 46E28B80-F248-11E8-B48F-1D18A9856A87 last_name: Lyudchik - first_name: Michał full_name: Januszewski, Michał last_name: Januszewski - first_name: Vitali full_name: Vistunou, Vitali id: 7e146587-8972-11ed-ae7b-d7a32ea86a81 last_name: Vistunou - first_name: Nathalie full_name: Agudelo Duenas, Nathalie id: 40E7F008-F248-11E8-B48F-1D18A9856A87 last_name: Agudelo Duenas - first_name: Jakob full_name: Vorlaufer, Jakob id: 937696FA-C996-11E9-8C7C-CF13E6697425 last_name: Vorlaufer orcid: 0009-0000-7590-3501 - 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: Caroline full_name: Kreuzinger, Caroline id: 382077BA-F248-11E8-B48F-1D18A9856A87 last_name: Kreuzinger - first_name: Bárbara full_name: Oliveira, Bárbara id: 3B03AA1A-F248-11E8-B48F-1D18A9856A87 last_name: Oliveira - first_name: Alban full_name: Cenameri, Alban id: 9ac8f577-2357-11eb-997a-e566c5550886 last_name: Cenameri - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Viren full_name: Jain, Viren last_name: Jain - 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: Tavakoli M, Lyudchik J, Januszewski M, et al. Light-microscopy based dense connectomic reconstruction of mammalian brain tissue. bioRxiv. doi:10.1101/2024.03.01.582884 apa: Tavakoli, M., Lyudchik, J., Januszewski, M., Vistunou, V., Agudelo Duenas, N., Vorlaufer, J., … Danzl, J. G. (n.d.). Light-microscopy based dense connectomic reconstruction of mammalian brain tissue. bioRxiv. https://doi.org/10.1101/2024.03.01.582884 chicago: Tavakoli, Mojtaba, Julia Lyudchik, Michał Januszewski, Vitali Vistunou, Nathalie Agudelo Duenas, Jakob Vorlaufer, Christoph M Sommer, et al. “Light-Microscopy Based Dense Connectomic Reconstruction of Mammalian Brain Tissue.” BioRxiv, n.d. https://doi.org/10.1101/2024.03.01.582884. ieee: M. Tavakoli et al., “Light-microscopy based dense connectomic reconstruction of mammalian brain tissue,” bioRxiv. . ista: Tavakoli M, Lyudchik J, Januszewski M, Vistunou V, Agudelo Duenas N, Vorlaufer J, Sommer CM, Kreuzinger C, Oliveira B, Cenameri A, Novarino G, Jain V, Danzl JG. Light-microscopy based dense connectomic reconstruction of mammalian brain tissue. bioRxiv, 10.1101/2024.03.01.582884. mla: Tavakoli, Mojtaba, et al. “Light-Microscopy Based Dense Connectomic Reconstruction of Mammalian Brain Tissue.” BioRxiv, doi:10.1101/2024.03.01.582884. short: M. Tavakoli, J. Lyudchik, M. Januszewski, V. Vistunou, N. Agudelo Duenas, J. Vorlaufer, C.M. Sommer, C. Kreuzinger, B. Oliveira, A. Cenameri, G. Novarino, V. Jain, J.G. Danzl, BioRxiv (n.d.). corr_author: '1' date_created: 2024-12-18T14:48:24Z date_published: 2024-07-08T00:00:00Z date_updated: 2026-04-28T13:33:34Z day: '08' department: - _id: GaNo - _id: JoDa doi: 10.1101/2024.03.01.582884 ec_funded: 1 language: - iso: eng license: https://creativecommons.org/licenses/by-nc-nd/4.0/ main_file_link: - open_access: '1' url: https://doi.org/10.1101/2024.03.01.582884 month: '07' oa: 1 oa_version: Preprint project: - _id: 6285a163-2b32-11ec-9570-8e204ca2dba5 grant_number: '26137' name: Studying Organelle Structure and Function at Nanoscale Resolution with Expansion Microscopy - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program - _id: 34ba8964-11ca-11ed-8bc3-e15864e7e9a6 grant_number: '101044865' name: Toward an understanding of the brain interstitial system and the extracellular proteome in health and autism spectrum disorders - _id: 26AA4EF2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets publication: bioRxiv publication_status: draft related_material: record: - id: '18681' relation: dissertation_contains status: public - id: '18674' relation: dissertation_contains status: public - id: '19704' relation: later_version status: public status: public title: Light-microscopy based dense connectomic reconstruction of mammalian brain tissue 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: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2024' ...