[{"page":"147","citation":{"chicago":"Knaus, Lisa. “The Metabolism of the Developing Brain : How Large Neutral Amino Acids Modulate Perinatal Neuronal Excitability and Survival.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:13107.","short":"L. Knaus, The Metabolism of the Developing Brain : How Large Neutral Amino Acids Modulate Perinatal Neuronal Excitability and Survival, Institute of Science and Technology Austria, 2023.","mla":"Knaus, Lisa. The Metabolism of the Developing Brain : How Large Neutral Amino Acids Modulate Perinatal Neuronal Excitability and Survival. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:13107.","apa":"Knaus, L. (2023). The metabolism of the developing brain : How large neutral amino acids modulate perinatal neuronal excitability and survival. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:13107","ieee":"L. Knaus, “The metabolism of the developing brain : How large neutral amino acids modulate perinatal neuronal excitability and survival,” Institute of Science and Technology Austria, 2023.","ista":"Knaus L. 2023. The metabolism of the developing brain : How large neutral amino acids modulate perinatal neuronal excitability and survival. Institute of Science and Technology Austria.","ama":"Knaus L. The metabolism of the developing brain : How large neutral amino acids modulate perinatal neuronal excitability and survival. 2023. doi:10.15479/at:ista:13107"},"date_published":"2023-05-31T00:00:00Z","day":"31","has_accepted_license":"1","article_processing_charge":"No","title":"The metabolism of the developing brain : How large neutral amino acids modulate perinatal neuronal excitability and survival","ddc":["570"],"status":"public","_id":"13107","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","file":[{"access_level":"closed","file_name":"Thesis_Lisa Knaus_approved_final.docx","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":12991551,"creator":"lknaus","relation":"source_file","file_id":"13112","checksum":"4b69a4ac0bbf4163d59c0b58dcb4f2c3","date_updated":"2023-06-01T13:48:41Z","date_created":"2023-06-01T13:48:41Z"},{"access_level":"open_access","file_name":"Thesis_Lisa Knaus_approved_final_pdfa2b.pdf","creator":"lknaus","content_type":"application/pdf","file_size":9309015,"file_id":"13114","relation":"main_file","checksum":"6903d152aa01181d87a696085af31c83","date_updated":"2023-06-07T08:41:49Z","date_created":"2023-06-02T09:47:29Z"}],"oa_version":"Published Version","alternative_title":["ISTA Thesis"],"type":"dissertation","abstract":[{"lang":"eng","text":"Within the human body, the brain exhibits the highest rate of energy consumption amongst all organs, with the majority of generated ATP being utilized to sustain neuronal activity. Therefore, the metabolism of the mature cerebral cortex is geared towards preserving metabolic homeostasis whilst generating significant amounts of energy. This requires a precise interplay between diverse metabolic pathways, spanning from a tissue-wide scale to the level of individual neurons. Disturbances to this delicate metabolic equilibrium, such as those resulting from maternal malnutrition\r\nor mutations affecting metabolic enzymes, often result in neuropathological variants of neurodevelopment. For instance, mutations in SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs), have been associated with autism and microcephaly. However, despite recent progress in the field, the extent of metabolic restructuring that occurs within the developing brain and the corresponding alterations in nutrient demands during various critical periods remain largely unknown. To investigate this, we performed metabolomic profiling of the murine cerebral cortex to characterize the metabolic state of the forebrain at different developmental stages. We found that the developing cortex undergoes substantial metabolic reprogramming, with specific sets of metabolites displaying stage-specific changes. According to our observations, we determined a distinct temporal period in postnatal development during which the cortex displays heightened reliance on LNAAs. Hence, using a conditional knock-out mouse model, we deleted Slc7a5 in neural cells, allowing us to monitor the impact of a perturbed neuronal metabolic state across multiple developmental stages of corticogenesis. We found that manipulating the levels of essential LNAAs in cortical neurons in vivo affects one particular perinatal developmental period critical for cortical network refinement. Abnormally low intracellular LNAA levels result in cell-autonomous alterations in neuronal lipid metabolism, excitability, and survival during this particular time window. Although most of the effects of Slc7a5 deletion on neuronal physiology are transient, derailment of these processes during this brief but crucial window leads to long-term circuit dysfunction in mice. In conclusion, out data indicate that the cerebral cortex undergoes significant metabolic reorganization during development. This process involves the intricate integration of multiple metabolic pathways to ensure optimal neuronal function throughout different developmental stages. Our findings offer a paradigm for understanding how neurons synchronize the expression of nutrient-related genes with their activity to allow proper brain maturation. Further, our results demonstrate that disruptions in these precisely calibrated metabolic processes during critical periods of brain development may result in neuropathological outcomes in mice and in humans."}],"project":[{"_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020"},{"name":"Molecular Drug Targets","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24"}],"oa":1,"supervisor":[{"full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"degree_awarded":"PhD","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"EM-Fac"}],"language":[{"iso":"eng"}],"doi":"10.15479/at:ista:13107","month":"05","publication_identifier":{"issn":["2663 - 337X"]},"publication_status":"published","publisher":"Institute of Science and Technology Austria","department":[{"_id":"GradSch"},{"_id":"GaNo"}],"year":"2023","date_updated":"2024-02-07T08:03:33Z","date_created":"2023-06-01T09:05:24Z","author":[{"last_name":"Knaus","first_name":"Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","full_name":"Knaus, Lisa"}],"related_material":{"record":[{"id":"12802","relation":"part_of_dissertation","status":"public"}]},"file_date_updated":"2023-06-07T08:41:49Z","ec_funded":1},{"_id":"12802","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ddc":["570"],"title":"Large neutral amino acid levels tune perinatal neuronal excitability and survival","status":"public","intvolume":" 186","file":[{"access_level":"open_access","file_name":"2023_Cell_Knaus.pdf","file_size":15712841,"content_type":"application/pdf","creator":"dernst","relation":"main_file","file_id":"12889","checksum":"47e94fbe19e86505b429cb7a5b503ce6","success":1,"date_created":"2023-05-02T09:26:21Z","date_updated":"2023-05-02T09:26:21Z"}],"oa_version":"Published Version","type":"journal_article","abstract":[{"lang":"eng","text":"Little is known about the critical metabolic changes that neural cells have to undergo during development and how temporary shifts in this program can influence brain circuitries and behavior. Inspired by the discovery that mutations in SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs), lead to autism, we employed metabolomic profiling to study the metabolic states of the cerebral cortex across different developmental stages. We found that the forebrain undergoes significant metabolic remodeling throughout development, with certain groups of metabolites showing stage-specific changes, but what are the consequences of perturbing this metabolic program? By manipulating Slc7a5 expression in neural cells, we found that the metabolism of LNAAs and lipids are interconnected in the cortex. Deletion of Slc7a5 in neurons affects the postnatal metabolic state, leading to a shift in lipid metabolism. Additionally, it causes stage- and cell-type-specific alterations in neuronal activity patterns, resulting in a long-term circuit dysfunction."}],"issue":"9","publication":"Cell","citation":{"ista":"Knaus L, Basilico B, Malzl D, Gerykova Bujalkova M, Smogavec M, Schwarz LA, Gorkiewicz S, Amberg N, Pauler F, Knittl-Frank C, Tassinari M, Maulide N, Rülicke T, Menche J, Hippenmeyer S, Novarino G. 2023. Large neutral amino acid levels tune perinatal neuronal excitability and survival. Cell. 186(9), 1950–1967.e25.","apa":"Knaus, L., Basilico, B., Malzl, D., Gerykova Bujalkova, M., Smogavec, M., Schwarz, L. A., … Novarino, G. (2023). Large neutral amino acid levels tune perinatal neuronal excitability and survival. Cell. Elsevier. https://doi.org/10.1016/j.cell.2023.02.037","ieee":"L. Knaus et al., “Large neutral amino acid levels tune perinatal neuronal excitability and survival,” Cell, vol. 186, no. 9. Elsevier, p. 1950–1967.e25, 2023.","ama":"Knaus L, Basilico B, Malzl D, et al. Large neutral amino acid levels tune perinatal neuronal excitability and survival. Cell. 2023;186(9):1950-1967.e25. doi:10.1016/j.cell.2023.02.037","chicago":"Knaus, Lisa, Bernadette Basilico, Daniel Malzl, Maria Gerykova Bujalkova, Mateja Smogavec, Lena A. Schwarz, Sarah Gorkiewicz, et al. “Large Neutral Amino Acid Levels Tune Perinatal Neuronal Excitability and Survival.” Cell. Elsevier, 2023. https://doi.org/10.1016/j.cell.2023.02.037.","mla":"Knaus, Lisa, et al. “Large Neutral Amino Acid Levels Tune Perinatal Neuronal Excitability and Survival.” Cell, vol. 186, no. 9, Elsevier, 2023, p. 1950–1967.e25, doi:10.1016/j.cell.2023.02.037.","short":"L. Knaus, B. Basilico, D. Malzl, M. Gerykova Bujalkova, M. Smogavec, L.A. Schwarz, S. Gorkiewicz, N. Amberg, F. Pauler, C. Knittl-Frank, M. Tassinari, N. Maulide, T. Rülicke, J. Menche, S. Hippenmeyer, G. Novarino, Cell 186 (2023) 1950–1967.e25."},"article_type":"original","page":"1950-1967.e25","date_published":"2023-04-27T00:00:00Z","scopus_import":"1","keyword":["General Biochemistry","Genetics and Molecular Biology"],"day":"27","article_processing_charge":"Yes (via OA deal)","has_accepted_license":"1","acknowledgement":"We thank A. Freeman and V. Voronin for technical assistance, S. Deixler, A. Stichelberger, M. Schunn, and the Preclinical Facility for managing our animal colony. We thank L. Andersen and J. Sonntag, who were involved in generating the MADM lines. We thank the ISTA LSF Mass Spectrometry Core Facility for assistance with the proteomic analysis, as well as the ISTA electron microscopy and Imaging and Optics facility for technical support. Metabolomics LC-MS/MS analysis was performed by the Metabolomics Facility at Vienna BioCenter Core Facilities (VBCF). We acknowledge the support of the EMBL Metabolomics Core Facility (MCF) for lipidomics and intracellular metabolomics mass spectrometry data acquisition and analysis. RNA sequencing was performed by the Next Generation Sequencing Facility at VBCF. Schematics were generated using Biorender.com. This work was supported by the Austrian Science Fund (FWF, DK W1232-B24) and by the European Union’s Horizon 2020 research and innovation program (ERC) grant 725780 (LinPro) to S.H. and 715508 (REVERSEAUTISM) to G.N.","year":"2023","publication_status":"published","department":[{"_id":"SiHi"},{"_id":"GaNo"}],"publisher":"Elsevier","author":[{"id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","first_name":"Lisa","last_name":"Knaus","full_name":"Knaus, Lisa"},{"full_name":"Basilico, Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","orcid":"0000-0003-1843-3173","first_name":"Bernadette","last_name":"Basilico"},{"full_name":"Malzl, Daniel","last_name":"Malzl","first_name":"Daniel"},{"first_name":"Maria","last_name":"Gerykova Bujalkova","full_name":"Gerykova Bujalkova, Maria"},{"full_name":"Smogavec, Mateja","first_name":"Mateja","last_name":"Smogavec"},{"full_name":"Schwarz, Lena A.","first_name":"Lena A.","last_name":"Schwarz"},{"id":"f141a35d-15a9-11ec-9fb2-fef6becc7b6f","last_name":"Gorkiewicz","first_name":"Sarah","full_name":"Gorkiewicz, Sarah"},{"first_name":"Nicole","last_name":"Amberg","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207","full_name":"Amberg, Nicole"},{"orcid":"0000-0002-7462-0048","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler","first_name":"Florian","full_name":"Pauler, Florian"},{"full_name":"Knittl-Frank, Christian","last_name":"Knittl-Frank","first_name":"Christian"},{"first_name":"Marianna","last_name":"Tassinari","id":"7af593f1-d44a-11ed-bf94-a3646a6bb35e","full_name":"Tassinari, Marianna"},{"full_name":"Maulide, Nuno","last_name":"Maulide","first_name":"Nuno"},{"last_name":"Rülicke","first_name":"Thomas","full_name":"Rülicke, Thomas"},{"full_name":"Menche, Jörg","last_name":"Menche","first_name":"Jörg"},{"orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","first_name":"Simon","full_name":"Hippenmeyer, Simon"},{"last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"}],"related_material":{"link":[{"description":"News on ISTA Website","relation":"press_release","url":"https://ista.ac.at/en/news/feed-them-or-lose-them/"}],"record":[{"id":"13107","relation":"dissertation_contains","status":"public"}]},"date_created":"2023-04-05T08:15:40Z","date_updated":"2024-02-07T08:03:32Z","volume":186,"file_date_updated":"2023-05-02T09:26:21Z","ec_funded":1,"external_id":{"isi":["000991468700001"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"quality_controlled":"1","isi":1,"project":[{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24","call_identifier":"FWF","name":"Molecular Drug Targets"},{"_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780","call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"},{"grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020"}],"doi":"10.1016/j.cell.2023.02.037","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"LifeSc"}],"language":[{"iso":"eng"}],"month":"04","publication_identifier":{"issn":["0092-8674"]}},{"ec_funded":1,"file_date_updated":"2023-08-04T13:19:47Z","publisher":"Institute of Science and Technology Austria","department":[{"_id":"JoDa"},{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"Bio"},{"_id":"RySh"}],"year":"2023","acknowledgement":"We thank Jakob Vorlaufer, Nathalie Agudelo-Dueñas, Wiebke Jahr, Andreas Wartak for microscope maintenance and troubleshooting, Caroline Kreuzinger, Anna Freeman, and Irene Erber for technical assistance and Matthias Tomschik for support with obtaining human samples. We gratefully acknowledge Eder Miguel for setting up webKnossos and Marek Šuplata for computational support and hardware control. We are grateful to Ryuichi Shigemoto and Bernd Bickel for generous support, and Michael Sixt and Scott Boyd (Stanford University) for discussions and critical reading of the manuscript. PSD95-HaloTag mice were kindly provided by Seth Grant (University of Edinburgh). We acknowledge expert support by IST Austria’s scientific computing, imaging and optics, preclinical, and lab support facilities, and by the Library and Miba machine shop.\r\nWe gratefully acknowledge funding by the following sources: \r\nAustrian Science Fund (FWF) grant I3600-B27 (JGD)\r\nAustrian Science Fund (FWF) grant DK W1232 (JGD, JMM)\r\nAustrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award (PJ)\r\nAustrian Science Funds (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27 (RH)\r\nGesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (JGD)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 715508 – REVERSEAUTISM (GN)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 692692 – GIANTSYN (PJ)\r\nMarie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (JMM, JL)\r\nMarie Skłodowska-Curie Actions Individual Fellowship 101026635 under the EU Horizon 2020 program (JFW)","date_created":"2023-06-07T07:15:12Z","date_updated":"2024-02-21T12:18:19Z","related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"14257"}],"link":[{"url":"https://pub.ista.ac.at/group_danzl/data/CATS/","relation":"research_data","description":"Original data for Fig. 5d, Fig. 5d (N2V) and Fig. 5f-i, provided via an external link due to the large size (>10GB) of the datasets. "}]},"contributor":[{"id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","first_name":"Julia M","last_name":"Michalska"},{"first_name":"Julia","last_name":"Lyudchik","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431","first_name":"Philipp","last_name":"Velicky"},{"last_name":"Stefanickova","first_name":"Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed"},{"orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E","last_name":"Watson","first_name":"Jake"},{"last_name":"Cenameri","first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"last_name":"Sommer","first_name":"Christoph M","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Amberg","first_name":"Nicole","orcid":"0000-0002-3183-8207","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Alessandro","last_name":"Venturino","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2356-9403"},{"last_name":"Roessler","first_name":"Karl"},{"last_name":"Czech","first_name":"Thomas"},{"first_name":"Romana","last_name":"Höftberger"},{"last_name":"Siegert","first_name":"Sandra","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Peter M","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804"}],"author":[{"full_name":"Danzl, Johann G","last_name":"Danzl","first_name":"Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"}],"month":"08","project":[{"grant_number":"I03600","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF"},{"grant_number":"W1232-B24","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Drug Targets"},{"grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"The Wittgenstein Prize"},{"name":"High content imaging to decode human immune cell interactions in health and allergic disease","_id":"23889792-32DE-11EA-91FC-C7463DDC885E"},{"_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020"},{"grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","call_identifier":"H2020","name":"International IST Doctoral Program"},{"call_identifier":"H2020","name":"Synaptic computations of the hippocampal CA3 circuitry","grant_number":"101026635","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9"}],"tmp":{"name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","image":"/images/cc_by_nc_sa.png","short":"CC BY-NC-SA (4.0)"},"oa":1,"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"doi":"10.15479/AT:ISTA:13126","type":"research_data","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."}],"ddc":["610"],"status":"public","title":"Research data for the publication \"Imaging brain tissue architecture across millimeter to nanometer 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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.).","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"},{"_id":"Bio"},{"_id":"RySh"}],"publisher":"Springer Nature","publication_status":"epub_ahead","related_material":{"record":[{"relation":"research_data","status":"public","id":"13126"}],"link":[{"url":"https://github.com/danzllab/CATS","relation":"software"}]},"author":[{"first_name":"Julia M","last_name":"Michalska","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3862-1235","full_name":"Michalska, Julia M"},{"first_name":"Julia","last_name":"Lyudchik","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia"},{"full_name":"Velicky, Philipp","first_name":"Philipp","last_name":"Velicky","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431"},{"last_name":"Korinkova","first_name":"Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","full_name":"Korinkova, Hana"},{"orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E","last_name":"Watson","first_name":"Jake","full_name":"Watson, Jake"},{"full_name":"Cenameri, Alban","last_name":"Cenameri","first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","first_name":"Christoph M","last_name":"Sommer","full_name":"Sommer, Christoph M"},{"full_name":"Amberg, Nicole","first_name":"Nicole","last_name":"Amberg","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207"},{"full_name":"Venturino, Alessandro","orcid":"0000-0003-2356-9403","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","last_name":"Venturino","first_name":"Alessandro"},{"last_name":"Roessler","first_name":"Karl","full_name":"Roessler, Karl"},{"full_name":"Czech, Thomas","last_name":"Czech","first_name":"Thomas"},{"full_name":"Höftberger, Romana","first_name":"Romana","last_name":"Höftberger"},{"full_name":"Siegert, Sandra","last_name":"Siegert","first_name":"Sandra","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Peter M","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M"},{"orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","first_name":"Johann G","full_name":"Danzl, Johann G"}],"date_updated":"2024-02-21T12:18:18Z","date_created":"2023-09-03T22:01:15Z","scopus_import":"1","article_processing_charge":"Yes (in subscription journal)","day":"31","citation":{"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.","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","ieee":"J. M. Michalska et al., “Imaging brain tissue architecture across millimeter to nanometer scales,” Nature Biotechnology. Springer Nature, 2023.","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","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.","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)."},"publication":"Nature Biotechnology","article_type":"original","date_published":"2023-08-31T00:00:00Z","type":"journal_article","abstract":[{"text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease.","lang":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"14257","status":"public","title":"Imaging brain tissue architecture across millimeter to nanometer scales","oa_version":"Published Version"},{"_id":"12140","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","title":"What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior","ddc":["570"],"status":"public","intvolume":" 16","oa_version":"Published Version","file":[{"file_name":"2022_FrontiersNeuroscience_Basilico.pdf","access_level":"open_access","creator":"dernst","content_type":"application/pdf","file_size":6399987,"file_id":"12352","relation":"main_file","date_updated":"2023-01-24T09:16:29Z","date_created":"2023-01-24T09:16:29Z","success":1,"checksum":"84696213ecf99182c58a9f34b9ff2e23"}],"type":"journal_article","abstract":[{"lang":"eng","text":"Microglia are dynamic cells, constantly surveying their surroundings and interacting with neurons and synapses. Indeed, a wealth of knowledge has revealed a critical role of microglia in modulating synaptic transmission and plasticity in the developing brain. In the past decade, novel pharmacological and genetic strategies have allowed the acute removal of microglia, opening the possibility to explore and understand the role of microglia also in the adult brain. In this review, we summarized and discussed the contribution of microglia depletion strategies to the current understanding of the role of microglia on synaptic function, learning and memory, and behavior both in physiological and pathological conditions. We first described the available microglia depletion methods highlighting their main strengths and weaknesses. We then reviewed the impact of microglia depletion on structural and functional synaptic plasticity. Next, we focused our analysis on the effects of microglia depletion on behavior, including general locomotor activity, sensory perception, motor function, sociability, learning and memory both in healthy animals and animal models of disease. Finally, we integrated the findings from the reviewed studies and discussed the emerging roles of microglia on the maintenance of synaptic function, learning, memory strength and forgetfulness, and the implications of microglia depletion in models of brain disease."}],"publication":"Frontiers in Cellular Neuroscience","citation":{"chicago":"Basilico, Bernadette, Laura Ferrucci, Azka Khan, Silvia Di Angelantonio, Davide Ragozzino, and Ingrid Reverte. “What Microglia Depletion Approaches Tell Us about the Role of Microglia on Synaptic Function and Behavior.” Frontiers in Cellular Neuroscience. Frontiers Media, 2022. https://doi.org/10.3389/fncel.2022.1022431.","mla":"Basilico, Bernadette, et al. “What Microglia Depletion Approaches Tell Us about the Role of Microglia on Synaptic Function and Behavior.” Frontiers in Cellular Neuroscience, vol. 16, 1022431, Frontiers Media, 2022, doi:10.3389/fncel.2022.1022431.","short":"B. Basilico, L. Ferrucci, A. Khan, S. Di Angelantonio, D. Ragozzino, I. Reverte, Frontiers in Cellular Neuroscience 16 (2022).","ista":"Basilico B, Ferrucci L, Khan A, Di Angelantonio S, Ragozzino D, Reverte I. 2022. What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior. Frontiers in Cellular Neuroscience. 16, 1022431.","apa":"Basilico, B., Ferrucci, L., Khan, A., Di Angelantonio, S., Ragozzino, D., & Reverte, I. (2022). What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior. Frontiers in Cellular Neuroscience. Frontiers Media. https://doi.org/10.3389/fncel.2022.1022431","ieee":"B. Basilico, L. Ferrucci, A. Khan, S. Di Angelantonio, D. Ragozzino, and I. Reverte, “What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior,” Frontiers in Cellular Neuroscience, vol. 16. Frontiers Media, 2022.","ama":"Basilico B, Ferrucci L, Khan A, Di Angelantonio S, Ragozzino D, Reverte I. What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior. Frontiers in Cellular Neuroscience. 2022;16. doi:10.3389/fncel.2022.1022431"},"article_type":"original","date_published":"2022-11-04T00:00:00Z","scopus_import":"1","keyword":["Cellular and Molecular Neuroscience"],"day":"04","article_processing_charge":"No","has_accepted_license":"1","acknowledgement":"The write-up of the review was supported by Sapienza University of Rome (Fondi di Ateneo, grant numbers #MA32117A7B698029 and #PH12017270934C3C to SD), Regione Lazio (POR FSE 2014/20, grant number #19036AP000000019 to SD), Fulbright 2019 (grant number\r\n#FSP-P005556 to SD), Institute Pasteur Italia (Fondi Cenci Bolognetti #363 to DR), and Network of European Funding for Neuroscience Research (ERA-NET NEURON Transnational\r\nResearch Projects on Neurodevelopmental Disorders 2021, grant acronym #JTC2021-SHANKAstro to DR).","year":"2022","pmid":1,"publication_status":"published","publisher":"Frontiers Media","department":[{"_id":"GaNo"}],"author":[{"full_name":"Basilico, Bernadette","orcid":"0000-0003-1843-3173","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","last_name":"Basilico","first_name":"Bernadette"},{"first_name":"Laura","last_name":"Ferrucci","full_name":"Ferrucci, Laura"},{"full_name":"Khan, Azka","first_name":"Azka","last_name":"Khan"},{"full_name":"Di Angelantonio, Silvia","last_name":"Di Angelantonio","first_name":"Silvia"},{"full_name":"Ragozzino, Davide","last_name":"Ragozzino","first_name":"Davide"},{"full_name":"Reverte, Ingrid","last_name":"Reverte","first_name":"Ingrid"}],"date_created":"2023-01-12T12:04:50Z","date_updated":"2023-08-04T08:56:10Z","volume":16,"article_number":"1022431","file_date_updated":"2023-01-24T09:16:29Z","external_id":{"isi":["000886526600001"],"pmid":["36406752"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"quality_controlled":"1","isi":1,"doi":"10.3389/fncel.2022.1022431","language":[{"iso":"eng"}],"month":"11","publication_identifier":{"issn":["1662-5102"]}}]