[{"corr_author":"1","language":[{"iso":"eng"}],"department":[{"_id":"GradSch"},{"_id":"JoCs"}],"date_created":"2025-03-25T11:22:38Z","publication_status":"published","degree_awarded":"PhD","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"abstract":[{"lang":"eng","text":"Making decisions requires flexibly adapting to changing environments, a process that\r\ndepends on accurately interpreting current contingencies and integrating them with\r\npast experience. Two brain regions are particularly critical for this process, the medial\r\nprefrontal cortex (mPFC) and the hippocampus. Using contextual information from the\r\nhippocampus, the mPFC selects relevant cognitive frameworks and suppresses\r\nirrelevant ones to guide appropriate actions. Several studies have shown that some\r\nmPFC pyramidal neurons become spatially tuned when spatial information is required\r\nto guide goal-directed behavior. However, the role of prefrontal spatial representations\r\nin learning and decision making is not well understood. This work aims to characterize\r\nthe role of mPFC spatial tuning in supporting a contextual association task. Rats were\r\ntrained to learn two cue–location associations on a radial arm maze over multiple days,\r\nwhile we simultaneously recorded from dorsal CA1 of the hippocampus and the\r\nprelimbic area of the mPFC. We describe a subset of spatially tuned hippocampal and\r\nprefrontal pyramidal neurons that “flicker” between multiple spatial representations on\r\ndifferent trials, suggesting dynamic, context-dependent coding. This flickering may\r\nprovide a substrate for how the network reorganizes in response to task demands,\r\nlikely by enabling the flexible evaluation of competing representations. "}],"supervisor":[{"first_name":"Jozsef L","id":"3FA14672-F248-11E8-B48F-1D18A9856A87","full_name":"Csicsvari, Jozsef L","last_name":"Csicsvari","orcid":"0000-0002-5193-4036"}],"keyword":["neuroscience","decision making","learning","cognitive flexibility","medial prefrontal cortex","hippocampus","electrophysiology"],"author":[{"full_name":"Cumpelik, Andrea D","last_name":"Cumpelik","first_name":"Andrea D","id":"3F158B32-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1727-6612"}],"file_date_updated":"2025-09-30T22:30:02Z","OA_embargo":"6 months","publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-056-5"]},"oa":1,"file":[{"relation":"main_file","access_level":"open_access","embargo":"2025-09-30","content_type":"application/pdf","checksum":"1c7573303d8e5f6da3eb03d59055390f","date_updated":"2025-09-30T22:30:02Z","file_id":"19457","date_created":"2025-03-25T11:07:55Z","creator":"acumpeli","file_name":"2025_Thesis_Cumpelik_corrections_PDFA.pdf","file_size":11869040},{"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","checksum":"b93265ebd9a53f7a14100d0d48b4ff5b","date_updated":"2025-09-30T22:30:02Z","file_id":"19458","date_created":"2025-03-25T11:08:05Z","file_name":"2025_Thesis_Cumpelik_corrections.docx","creator":"acumpeli","file_size":20436467,"relation":"source_file","access_level":"closed","embargo_to":"open_access"}],"doi":"10.15479/AT-ISTA-19456","OA_place":"publisher","alternative_title":["ISTA Thesis"],"ddc":["612"],"citation":{"short":"A.D. Cumpelik, The Role of Prefrontal Spatial Coding in Supporting a Contextual Association Task, Institute of Science and Technology Austria, 2025.","mla":"Cumpelik, Andrea D. <i>The Role of Prefrontal Spatial Coding in Supporting a Contextual Association Task</i>. Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-19456\">10.15479/AT-ISTA-19456</a>.","ieee":"A. D. Cumpelik, “The role of prefrontal spatial coding in supporting a contextual association task,” Institute of Science and Technology Austria, 2025.","ama":"Cumpelik AD. The role of prefrontal spatial coding in supporting a contextual association task. 2025. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-19456\">10.15479/AT-ISTA-19456</a>","apa":"Cumpelik, A. D. (2025). <i>The role of prefrontal spatial coding in supporting a contextual association task</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-19456\">https://doi.org/10.15479/AT-ISTA-19456</a>","chicago":"Cumpelik, Andrea D. “The Role of Prefrontal Spatial Coding in Supporting a Contextual Association Task.” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT-ISTA-19456\">https://doi.org/10.15479/AT-ISTA-19456</a>.","ista":"Cumpelik AD. 2025. The role of prefrontal spatial coding in supporting a contextual association task. Institute of Science and Technology Austria."},"article_processing_charge":"No","title":"The role of prefrontal spatial coding in supporting a contextual association task","month":"02","_id":"19456","page":"96","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","year":"2025","oa_version":"Published Version","date_updated":"2026-04-07T12:37:58Z","has_accepted_license":"1","date_published":"2025-02-18T00:00:00Z","day":"18","type":"dissertation","publisher":"Institute of Science and Technology Austria","status":"public"},{"pmid":1,"acknowledgement":"The research leading to these results has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme grant agreement No 742985 and Austrian Science Fund (FWF): I3630-775 B25 to J.F. This research was also supported by the Lab Support Facility (LSF) and the Imaging and Optics Facility (IOF) of IST Austria, namely Tereza Bělinová for her help with the imaging. JS was supported by FemTECH fellowship.","DOAJ_listed":"1","file":[{"success":1,"relation":"main_file","access_level":"open_access","file_size":11451904,"date_created":"2024-04-03T13:18:00Z","file_id":"15288","file_name":"2024_eLife_Kulich.pdf","creator":"dernst","date_updated":"2024-04-03T13:18:00Z","checksum":"a73a84d3bf97a6d09d24308ca6dd0a0c","content_type":"application/pdf"}],"publication_identifier":{"issn":["2050-084X"]},"oa":1,"scopus_import":"1","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"file_date_updated":"2024-04-03T13:18:00Z","author":[{"id":"57a1567c-8314-11eb-9063-c9ddc3451a54","first_name":"Ivan","last_name":"Kulich","full_name":"Kulich, Ivan"},{"id":"07cf4637-baaf-11ee-9227-e1de57d1d69b","first_name":"Julia","full_name":"Schmid, Julia","last_name":"Schmid"},{"last_name":"Teplova","full_name":"Teplova, Anastasiia","id":"e3736151-106c-11ec-b916-c2558e2762c6","first_name":"Anastasiia"},{"id":"44B04502-A9ED-11E9-B6FC-583AE6697425","first_name":"Linlin","full_name":"Qi, Linlin","last_name":"Qi","orcid":"0000-0001-5187-8401"},{"last_name":"Friml","full_name":"Friml, Jiří","first_name":"Jiří","id":"4159519E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8302-7596"}],"publication":"eLife","intvolume":"        12","ec_funded":1,"article_number":"91523","abstract":[{"text":"Root gravitropic bending represents a fundamental aspect of terrestrial plant physiology. Gravity is perceived by sedimentation of starch-rich plastids (statoliths) to the bottom of the central root cap cells. Following gravity perception, intercellular auxin transport is redirected downwards leading to an asymmetric auxin accumulation at the lower root side causing inhibition of cell expansion, ultimately resulting in downwards bending. How gravity-induced statoliths repositioning is translated into asymmetric auxin distribution remains unclear despite PIN auxin efflux carriers and the Negative Gravitropic Response of roots (NGR) proteins polarize along statolith sedimentation, thus providing a plausible mechanism for auxin flow redirection. In this study, using a functional NGR1-GFP construct, we visualized the NGR1 localization on the statolith surface and plasma membrane (PM) domains in close proximity to the statoliths, correlating with their movements. We determined that NGR1 binding to these PM domains is indispensable for NGR1 functionality and relies on cysteine acylation and adjacent polybasic regions as well as on lipid and sterol PM composition. Detailed timing of the early events following graviperception suggested that both NGR1 repolarization and initial auxin asymmetry precede the visible PIN3 polarization. This discrepancy motivated us to unveil a rapid, NGR-dependent translocation of PIN-activating AGCVIII kinase D6PK towards lower PMs of gravity-perceiving cells, thus providing an attractive model for rapid redirection of auxin fluxes following gravistimulation.","lang":"eng"}],"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"volume":12,"quality_controlled":"1","date_created":"2024-04-02T11:35:58Z","external_id":{"pmid":["38441122"]},"department":[{"_id":"JiFr"}],"corr_author":"1","language":[{"iso":"eng"}],"publication_status":"published","publisher":"eLife Sciences Publications","type":"journal_article","day":"05","status":"public","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","has_accepted_license":"1","date_published":"2024-03-05T00:00:00Z","project":[{"_id":"261099A6-B435-11E9-9278-68D0E5697425","grant_number":"742985","call_identifier":"H2020","name":"Tracing Evolution of Auxin Transport and Polarity in Plants"},{"grant_number":"I03630","_id":"26538374-B435-11E9-9278-68D0E5697425","name":"Molecular mechanisms of endocytic cargo recognition in plants","call_identifier":"FWF"}],"date_updated":"2025-04-23T07:45:02Z","oa_version":"Published Version","year":"2024","article_processing_charge":"Yes","related_material":{"link":[{"description":"News on ISTA website","relation":"press_release","url":"https://ista.ac.at/en/news/beneath-the-surface/"}]},"citation":{"ama":"Kulich I, Schmid J, Teplova A, Qi L, Friml J. Rapid translocation of NGR proteins driving polarization of PIN-activating D6 protein kinase during root gravitropism. <i>eLife</i>. 2024;12. doi:<a href=\"https://doi.org/10.7554/elife.91523\">10.7554/elife.91523</a>","apa":"Kulich, I., Schmid, J., Teplova, A., Qi, L., &#38; Friml, J. (2024). Rapid translocation of NGR proteins driving polarization of PIN-activating D6 protein kinase during root gravitropism. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.91523\">https://doi.org/10.7554/elife.91523</a>","chicago":"Kulich, Ivan, Julia Schmid, Anastasiia Teplova, Linlin Qi, and Jiří Friml. “Rapid Translocation of NGR Proteins Driving Polarization of PIN-Activating D6 Protein Kinase during Root Gravitropism.” <i>ELife</i>. eLife Sciences Publications, 2024. <a href=\"https://doi.org/10.7554/elife.91523\">https://doi.org/10.7554/elife.91523</a>.","ista":"Kulich I, Schmid J, Teplova A, Qi L, Friml J. 2024. Rapid translocation of NGR proteins driving polarization of PIN-activating D6 protein kinase during root gravitropism. eLife. 12, 91523.","mla":"Kulich, Ivan, et al. “Rapid Translocation of NGR Proteins Driving Polarization of PIN-Activating D6 Protein Kinase during Root Gravitropism.” <i>ELife</i>, vol. 12, 91523, eLife Sciences Publications, 2024, doi:<a href=\"https://doi.org/10.7554/elife.91523\">10.7554/elife.91523</a>.","short":"I. Kulich, J. Schmid, A. Teplova, L. Qi, J. Friml, ELife 12 (2024).","ieee":"I. Kulich, J. Schmid, A. Teplova, L. Qi, and J. Friml, “Rapid translocation of NGR proteins driving polarization of PIN-activating D6 protein kinase during root gravitropism,” <i>eLife</i>, vol. 12. eLife Sciences Publications, 2024."},"_id":"15257","month":"03","title":"Rapid translocation of NGR proteins driving polarization of PIN-activating D6 protein kinase during root gravitropism","article_type":"original","doi":"10.7554/elife.91523","ddc":["580"]},{"ddc":["570"],"doi":"10.1016/j.xpro.2023.102771","article_type":"review","_id":"14683","title":"Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry","month":"03","article_processing_charge":"Yes (in subscription journal)","citation":{"chicago":"Amberg, Nicole, Giselle T Cheung, and Simon Hippenmeyer. “Protocol for Sorting Cells from Mouse Brains Labeled with Mosaic Analysis with Double Markers by Flow Cytometry.” <i>STAR Protocols</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">https://doi.org/10.1016/j.xpro.2023.102771</a>.","ista":"Amberg N, Cheung GT, Hippenmeyer S. 2024. Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. STAR Protocols. 5(1), 102771.","ama":"Amberg N, Cheung GT, Hippenmeyer S. Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. <i>STAR Protocols</i>. 2024;5(1). doi:<a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">10.1016/j.xpro.2023.102771</a>","apa":"Amberg, N., Cheung, G. T., &#38; Hippenmeyer, S. (2024). Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. <i>STAR Protocols</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">https://doi.org/10.1016/j.xpro.2023.102771</a>","ieee":"N. Amberg, G. T. Cheung, and S. Hippenmeyer, “Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry,” <i>STAR Protocols</i>, vol. 5, no. 1. Elsevier, 2024.","short":"N. Amberg, G.T. Cheung, S. Hippenmeyer, STAR Protocols 5 (2024).","mla":"Amberg, Nicole, et al. “Protocol for Sorting Cells from Mouse Brains Labeled with Mosaic Analysis with Double Markers by Flow Cytometry.” <i>STAR Protocols</i>, vol. 5, no. 1, 102771, Elsevier, 2024, doi:<a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">10.1016/j.xpro.2023.102771</a>."},"date_published":"2024-03-15T00:00:00Z","has_accepted_license":"1","project":[{"grant_number":"T01031","_id":"268F8446-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Role of Eed in neural stem cell lineage progression"},{"call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411"},{"grant_number":"F7805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression"},{"call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425"}],"oa_version":"Published Version","year":"2024","date_updated":"2025-04-15T08:23:06Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"publisher":"Elsevier","type":"journal_article","day":"15","issue":"1","publication_status":"published","department":[{"_id":"SiHi"}],"external_id":{"pmid":["38070137"]},"date_created":"2023-12-13T11:48:05Z","corr_author":"1","language":[{"iso":"eng"}],"volume":5,"quality_controlled":"1","abstract":[{"text":"Mosaic analysis with double markers (MADM) technology enables the generation of genetic mosaic tissue in mice and high-resolution phenotyping at the individual cell level. Here, we present a protocol for isolating MADM-labeled cells with high yield for downstream molecular analyses using fluorescence-activated cell sorting (FACS). We describe steps for generating MADM-labeled mice, perfusion, single-cell suspension, and debris removal. We then detail procedures for cell sorting by FACS and downstream analysis. This protocol is suitable for embryonic to adult mice.\r\nFor complete details on the use and execution of this protocol, please refer to Contreras et al. (2021).1","lang":"eng"}],"article_number":"102771","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"author":[{"orcid":"0000-0002-3183-8207","first_name":"Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","last_name":"Amberg","full_name":"Amberg, Nicole"},{"first_name":"Giselle T","id":"471195F6-F248-11E8-B48F-1D18A9856A87","full_name":"Cheung, Giselle T","last_name":"Cheung","orcid":"0000-0001-8457-2572"},{"orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon"}],"file_date_updated":"2024-07-16T11:50:03Z","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Neuroscience"],"scopus_import":"1","publication":"STAR Protocols","ec_funded":1,"intvolume":"         5","acknowledgement":"This research was supported by the Scientific Service Units (SSU) at IST Austria through resources provided by the Imaging & Optics Facility (IOF) and Preclinical Facilities (PCF). N.A. received support from FWF Firnberg-Programme (T 1031). G.C. received support from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 754411 as an ISTplus postdoctoral fellow. This work was also supported by IST Austria institutional funds, FWF SFB F78 to S.H., and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 725780 LinPro) to S.H.","file":[{"relation":"main_file","access_level":"open_access","success":1,"date_updated":"2024-07-16T11:50:03Z","content_type":"application/pdf","checksum":"3f0ee62e04bf5a44b45b035662826e95","file_size":8871807,"date_created":"2024-07-16T11:50:03Z","file_id":"17260","file_name":"2024_STARProtoc_Amberg.pdf","creator":"dernst"}],"pmid":1,"publication_identifier":{"issn":["2666-1667"]},"oa":1},{"volume":13,"quality_controlled":"1","abstract":[{"text":"The GNOM (GN) Guanine nucleotide Exchange Factor for ARF small GTPases (ARF-GEF) is among the best studied trafficking regulators in plants, playing crucial and unique developmental roles in patterning and polarity. The current models place GN at the Golgi apparatus (GA), where it mediates secretion/recycling, and at the plasma membrane (PM) presumably contributing to clathrin-mediated endocytosis (CME). The mechanistic basis of the developmental function of GN, distinct from the other ARF-GEFs including its closest homologue GNOM-LIKE1 (GNL1), remains elusive. Insights from this study largely extend the current notions of GN function. We show that GN, but not GNL1, localizes to the cell periphery at long-lived structures distinct from clathrin-coated pits, while CME and secretion proceed normally in <jats:italic>gn</jats:italic> knockouts. The functional GN mutant variant GN<jats:sup>fewerroots</jats:sup>, absent from the GA, suggests that the cell periphery is the major site of GN action responsible for its developmental function. Following inhibition by Brefeldin A, GN, but not GNL1, relocates to the PM likely on exocytic vesicles, suggesting selective molecular associations en route to the cell periphery. A study of GN-GNL1 chimeric ARF-GEFs indicates that all GN domains contribute to the specific GN function in a partially redundant manner. Together, this study offers significant steps toward the elucidation of the mechanism underlying unique cellular and development functions of GNOM.","lang":"eng"}],"publication_status":"published","external_id":{"pmid":["38381485"],"isi":["001174278000001"]},"department":[{"_id":"JiFr"}],"date_created":"2024-02-27T07:10:11Z","language":[{"iso":"eng"}],"corr_author":"1","DOAJ_listed":"1","file":[{"success":1,"relation":"main_file","access_level":"open_access","date_created":"2024-07-22T11:51:50Z","file_id":"17310","file_name":"2024_eLife_Adamowski.pdf","creator":"dernst","file_size":15675744,"checksum":"b2b2d583b433823af731842f1420113e","content_type":"application/pdf","date_updated":"2024-07-22T11:51:50Z"}],"acknowledgement":"The authors would like to gratefully acknowledge Dr Xixi Zhang for cloning the GNL1/pDONR221 construct and for useful discussions.H2020 European Research Council Advanced Grant ETAP742985 to Jiří Friml, Austrian Science Fund I 3630-B25 to Jiří Friml","pmid":1,"publication_identifier":{"issn":["2050-084X"]},"oa":1,"APC_amount":"2792,52 EUR","scopus_import":"1","author":[{"last_name":"Adamowski","full_name":"Adamowski, Maciek","first_name":"Maciek","id":"45F536D2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6463-5257"},{"id":"83c17ce3-15b2-11ec-abd3-f486545870bd","first_name":"Ivana","full_name":"Matijevic, Ivana","last_name":"Matijevic"},{"first_name":"Jiří","id":"4159519E-F248-11E8-B48F-1D18A9856A87","last_name":"Friml","full_name":"Friml, Jiří","orcid":"0000-0002-8302-7596"}],"keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"file_date_updated":"2024-07-22T11:51:50Z","publication":"eLife","ec_funded":1,"intvolume":"        13","isi":1,"_id":"15033","title":"Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery","month":"02","article_processing_charge":"Yes","citation":{"apa":"Adamowski, M., Matijevic, I., &#38; Friml, J. (2024). Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.68993\">https://doi.org/10.7554/elife.68993</a>","ama":"Adamowski M, Matijevic I, Friml J. Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery. <i>eLife</i>. 2024;13. doi:<a href=\"https://doi.org/10.7554/elife.68993\">10.7554/elife.68993</a>","ista":"Adamowski M, Matijevic I, Friml J. 2024. Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery. eLife. 13.","chicago":"Adamowski, Maciek, Ivana Matijevic, and Jiří Friml. “Developmental Patterning Function of GNOM ARF-GEF Mediated from the Cell Periphery.” <i>ELife</i>. eLife Sciences Publications, 2024. <a href=\"https://doi.org/10.7554/elife.68993\">https://doi.org/10.7554/elife.68993</a>.","mla":"Adamowski, Maciek, et al. “Developmental Patterning Function of GNOM ARF-GEF Mediated from the Cell Periphery.” <i>ELife</i>, vol. 13, eLife Sciences Publications, 2024, doi:<a href=\"https://doi.org/10.7554/elife.68993\">10.7554/elife.68993</a>.","short":"M. Adamowski, I. Matijevic, J. Friml, ELife 13 (2024).","ieee":"M. Adamowski, I. Matijevic, and J. Friml, “Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery,” <i>eLife</i>, vol. 13. eLife Sciences Publications, 2024."},"ddc":["580"],"doi":"10.7554/elife.68993","OA_place":"publisher","article_type":"original","OA_type":"gold","status":"public","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"type":"journal_article","publisher":"eLife Sciences Publications","day":"21","project":[{"grant_number":"742985","_id":"261099A6-B435-11E9-9278-68D0E5697425","name":"Tracing Evolution of Auxin Transport and Polarity in Plants","call_identifier":"H2020"},{"grant_number":"I03630","_id":"26538374-B435-11E9-9278-68D0E5697425","name":"Molecular mechanisms of endocytic cargo recognition in plants","call_identifier":"FWF"},{"name":"FWF Open Access Fund","call_identifier":"FWF","_id":"3AC91DDA-15DF-11EA-824D-93A3E7B544D1"}],"date_published":"2024-02-21T00:00:00Z","has_accepted_license":"1","year":"2024","oa_version":"Published Version","date_updated":"2025-10-15T06:31:47Z","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345"},{"publication_identifier":{"issn":["0022-3077"],"eissn":["1522-1598"]},"pmid":1,"acknowledgement":"The authors gratefully thank Dr. Silvia Arber, University of Basel and Friedrich Miescher Institute for Biomedical Research, for support and in whose lab the data were collected. For advice on statistical analysis, we thank Michael Bottomley from the Statistical Consulting Center, College of Science and Mathematics, Wright State University.","intvolume":"       129","isi":1,"publication":"Journal of Neurophysiology","keyword":["Physiology","General Neuroscience"],"author":[{"full_name":"Ladle, David R.","last_name":"Ladle","first_name":"David R."},{"full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061"}],"scopus_import":"1","abstract":[{"lang":"eng","text":"Presynaptic inputs determine the pattern of activation of postsynaptic neurons in a neural circuit. Molecular and genetic pathways that regulate the selective formation of subsets of presynaptic inputs are largely unknown, despite significant understanding of the general process of synaptogenesis. In this study, we have begun to identify such factors using the spinal monosynaptic stretch reflex circuit as a model system. In this neuronal circuit, Ia proprioceptive afferents establish monosynaptic connections with spinal motor neurons that project to the same muscle (termed homonymous connections) or muscles with related or synergistic function. However, monosynaptic connections are not formed with motor neurons innervating muscles with antagonistic functions. The ETS transcription factor ER81 (also known as ETV1) is expressed by all proprioceptive afferents, but only a small set of motor neuron pools in the lumbar spinal cord of the mouse. Here we use conditional mouse genetic techniques to eliminate Er81 expression selectively from motor neurons. We find that ablation of Er81 in motor neurons reduces synaptic inputs from proprioceptive afferents conveying information from homonymous and synergistic muscles, with no change observed in the connectivity pattern from antagonistic proprioceptive afferents. In summary, these findings suggest a role for ER81 in defined motor neuron pools to control the assembly of specific presynaptic inputs and thereby influence the profile of activation of these motor neurons."}],"quality_controlled":"1","volume":129,"language":[{"iso":"eng"}],"date_created":"2023-02-15T14:46:14Z","department":[{"_id":"SiHi"}],"external_id":{"pmid":["36695533"],"isi":["000957721600001"]},"publication_status":"published","issue":"3","publisher":"American Physiological Society","day":"01","type":"journal_article","status":"public","page":"501-512","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","date_updated":"2024-10-21T06:01:28Z","year":"2023","oa_version":"None","date_published":"2023-03-01T00:00:00Z","citation":{"short":"D.R. Ladle, S. Hippenmeyer, Journal of Neurophysiology 129 (2023) 501–512.","mla":"Ladle, David R., and Simon Hippenmeyer. “Loss of ETV1/ER81 in Motor Neurons Leads to Reduced Monosynaptic Inputs from Proprioceptive Sensory Neurons.” <i>Journal of Neurophysiology</i>, vol. 129, no. 3, American Physiological Society, 2023, pp. 501–12, doi:<a href=\"https://doi.org/10.1152/jn.00172.2022\">10.1152/jn.00172.2022</a>.","ieee":"D. R. Ladle and S. Hippenmeyer, “Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons,” <i>Journal of Neurophysiology</i>, vol. 129, no. 3. American Physiological Society, pp. 501–512, 2023.","apa":"Ladle, D. R., &#38; Hippenmeyer, S. (2023). Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons. <i>Journal of Neurophysiology</i>. American Physiological Society. <a href=\"https://doi.org/10.1152/jn.00172.2022\">https://doi.org/10.1152/jn.00172.2022</a>","ama":"Ladle DR, Hippenmeyer S. Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons. <i>Journal of Neurophysiology</i>. 2023;129(3):501-512. doi:<a href=\"https://doi.org/10.1152/jn.00172.2022\">10.1152/jn.00172.2022</a>","ista":"Ladle DR, Hippenmeyer S. 2023. Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons. Journal of Neurophysiology. 129(3), 501–512.","chicago":"Ladle, David R., and Simon Hippenmeyer. “Loss of ETV1/ER81 in Motor Neurons Leads to Reduced Monosynaptic Inputs from Proprioceptive Sensory Neurons.” <i>Journal of Neurophysiology</i>. American Physiological Society, 2023. <a href=\"https://doi.org/10.1152/jn.00172.2022\">https://doi.org/10.1152/jn.00172.2022</a>."},"article_processing_charge":"No","month":"03","title":"Loss of ETV1/ER81 in motor neurons leads to reduced monosynaptic inputs from proprioceptive sensory neurons","_id":"12562","article_type":"original","doi":"10.1152/jn.00172.2022"},{"publication_status":"published","external_id":{"isi":["000953497700001"],"pmid":["36842274"]},"department":[{"_id":"SiHi"}],"date_created":"2023-02-26T12:24:21Z","language":[{"iso":"eng"}],"corr_author":"1","volume":79,"quality_controlled":"1","abstract":[{"lang":"eng","text":"How to generate a brain of correct size and with appropriate cell-type diversity during development is a major question in Neuroscience. In the developing neocortex, radial glial progenitor (RGP) cells are the main neural stem cells that produce cortical excitatory projection neurons, glial cells, and establish the prospective postnatal stem cell niche in the lateral ventricles. RGPs follow a tightly orchestrated developmental program that when disrupted can result in severe cortical malformations such as microcephaly and megalencephaly. The precise cellular and molecular mechanisms instructing faithful RGP lineage progression are however not well understood. This review will summarize recent conceptual advances that contribute to our understanding of the general principles of RGP lineage progression."}],"article_number":"102695","author":[{"last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061"}],"file_date_updated":"2023-08-16T12:29:06Z","keyword":["General Neuroscience"],"publication":"Current Opinion in Neurobiology","scopus_import":"1","ec_funded":1,"intvolume":"        79","isi":1,"acknowledgement":"I wish to thank all current and past members of the Hippenmeyer laboratory at ISTA for exciting discussions on the subject of this review. I apologize to colleagues whose work I could not cite and/or discuss in the frame of the available space. Work in the Hippenmeyer laboratory on the\r\ndiscussed topic is supported by ISTA institutional funds, FWF SFB F78 to S.H., and the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (grant agree-ment no. 725780 LinPro) to SH.","file":[{"date_updated":"2023-08-16T12:29:06Z","content_type":"application/pdf","checksum":"4d11c4ca87e6cbc4d2ac46d3225ea615","file_size":1787894,"date_created":"2023-08-16T12:29:06Z","file_id":"14071","creator":"dernst","file_name":"2023_CurrentOpinionNeurobio_Hippenmeyer.pdf","relation":"main_file","access_level":"open_access","success":1}],"pmid":1,"publication_identifier":{"issn":["0959-4388"]},"oa":1,"ddc":["570"],"doi":"10.1016/j.conb.2023.102695","article_type":"review","_id":"12679","title":"Principles of neural stem cell lineage progression: Insights from developing cerebral cortex","month":"04","article_processing_charge":"Yes (via OA deal)","citation":{"apa":"Hippenmeyer, S. (2023). Principles of neural stem cell lineage progression: Insights from developing cerebral cortex. <i>Current Opinion in Neurobiology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.conb.2023.102695\">https://doi.org/10.1016/j.conb.2023.102695</a>","ama":"Hippenmeyer S. Principles of neural stem cell lineage progression: Insights from developing cerebral cortex. <i>Current Opinion in Neurobiology</i>. 2023;79(4). doi:<a href=\"https://doi.org/10.1016/j.conb.2023.102695\">10.1016/j.conb.2023.102695</a>","ista":"Hippenmeyer S. 2023. Principles of neural stem cell lineage progression: Insights from developing cerebral cortex. Current Opinion in Neurobiology. 79(4), 102695.","chicago":"Hippenmeyer, Simon. “Principles of Neural Stem Cell Lineage Progression: Insights from Developing Cerebral Cortex.” <i>Current Opinion in Neurobiology</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.conb.2023.102695\">https://doi.org/10.1016/j.conb.2023.102695</a>.","short":"S. Hippenmeyer, Current Opinion in Neurobiology 79 (2023).","mla":"Hippenmeyer, Simon. “Principles of Neural Stem Cell Lineage Progression: Insights from Developing Cerebral Cortex.” <i>Current Opinion in Neurobiology</i>, vol. 79, no. 4, 102695, Elsevier, 2023, doi:<a href=\"https://doi.org/10.1016/j.conb.2023.102695\">10.1016/j.conb.2023.102695</a>.","ieee":"S. Hippenmeyer, “Principles of neural stem cell lineage progression: Insights from developing cerebral cortex,” <i>Current Opinion in Neurobiology</i>, vol. 79, no. 4. Elsevier, 2023."},"has_accepted_license":"1","date_published":"2023-04-01T00:00:00Z","project":[{"grant_number":"F7805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression"},{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020","grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425"}],"year":"2023","oa_version":"Published Version","date_updated":"2025-04-15T08:23:06Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"type":"journal_article","day":"01","publisher":"Elsevier","issue":"4"},{"file":[{"file_name":"2022_MolecularAutism_Schaaf.pdf","creator":"dernst","file_id":"11461","date_created":"2022-06-24T08:22:59Z","file_size":7552298,"content_type":"application/pdf","checksum":"525d2618e855139089bbfc3e3d49d1b2","date_updated":"2022-06-24T08:22:59Z","success":1,"access_level":"open_access","relation":"main_file"}],"acknowledgement":"This study was funded by NIMH R21MH115347 to KSZ. KSZ is further supported by Shriners Hospitals for Children.\r\nWe would like to thank Angelo Harlan de Crescenzo for early contributions to this project.","pmid":1,"oa":1,"publication_identifier":{"issn":["2040-2392"]},"publication":"Molecular Autism","file_date_updated":"2022-06-24T08:22:59Z","scopus_import":"1","author":[{"first_name":"Zachary A.","last_name":"Schaaf","full_name":"Schaaf, Zachary A."},{"full_name":"Tat, Lyvin","last_name":"Tat","first_name":"Lyvin"},{"first_name":"Noemi","full_name":"Cannizzaro, Noemi","last_name":"Cannizzaro"},{"first_name":"Ralph","full_name":"Green, Ralph","last_name":"Green"},{"first_name":"Thomas","full_name":"Rülicke, Thomas","last_name":"Rülicke"},{"first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061"},{"first_name":"Konstantinos S.","last_name":"Zarbalis","full_name":"Zarbalis, Konstantinos S."}],"keyword":["Psychiatry and Mental health","Developmental Biology","Developmental Neuroscience","Molecular Biology"],"intvolume":"        13","isi":1,"volume":13,"quality_controlled":"1","abstract":[{"text":"Background: Proper cerebral cortical development depends on the tightly orchestrated migration of newly born neurons from the inner ventricular and subventricular zones to the outer cortical plate. Any disturbance in this process during prenatal stages may lead to neuronal migration disorders (NMDs), which can vary in extent from focal to global. Furthermore, NMDs show a substantial comorbidity with other neurodevelopmental disorders, notably autism spectrum disorders (ASDs). Our previous work demonstrated focal neuronal migration defects in mice carrying loss-of-function alleles of the recognized autism risk gene WDFY3. However, the cellular origins of these defects in Wdfy3 mutant mice remain elusive and uncovering it will provide critical insight into WDFY3-dependent disease pathology.\r\nMethods: Here, in an effort to untangle the origins of NMDs in Wdfy3lacZ mice, we employed mosaic analysis with double markers (MADM). MADM technology enabled us to genetically distinctly track and phenotypically analyze mutant and wild-type cells concomitantly in vivo using immunofluorescent techniques.\r\nResults: We revealed a cell autonomous requirement of WDFY3 for accurate laminar positioning of cortical projection neurons and elimination of mispositioned cells during early postnatal life. In addition, we identified significant deviations in dendritic arborization, as well as synaptic density and morphology between wild type, heterozygous, and homozygous Wdfy3 mutant neurons in Wdfy3-MADM reporter mice at postnatal stages.\r\nLimitations: While Wdfy3 mutant mice have provided valuable insight into prenatal aspects of ASD pathology that remain inaccessible to investigation in humans, like most animal models, they do not a perfectly replicate all aspects of human ASD biology. The lack of human data makes it indeterminate whether morphological deviations described here apply to ASD patients or some of the other neurodevelopmental conditions associated with WDFY3 mutation.\r\nConclusions: Our genetic approach revealed several cell autonomous requirements of WDFY3 in neuronal development that could underlie the pathogenic mechanisms of WDFY3-related neurodevelopmental conditions. The results are also consistent with findings in other ASD animal models and patients and suggest an important role for WDFY3 in regulating neuronal function and interconnectivity in postnatal life.","lang":"eng"}],"article_number":"27","publication_status":"published","department":[{"_id":"SiHi"}],"external_id":{"pmid":["35733184"],"isi":["000814641400001"]},"date_created":"2022-06-23T14:28:55Z","language":[{"iso":"eng"}],"status":"public","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"day":"22","publisher":"Springer Nature","type":"journal_article","has_accepted_license":"1","date_published":"2022-06-22T00:00:00Z","oa_version":"Published Version","year":"2022","date_updated":"2025-06-11T13:34:57Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"11460","title":"WDFY3 mutation alters laminar position and morphology of cortical neurons","month":"06","article_processing_charge":"No","citation":{"short":"Z.A. Schaaf, L. Tat, N. Cannizzaro, R. Green, T. Rülicke, S. Hippenmeyer, K.S. Zarbalis, Molecular Autism 13 (2022).","mla":"Schaaf, Zachary A., et al. “WDFY3 Mutation Alters Laminar Position and Morphology of Cortical Neurons.” <i>Molecular Autism</i>, vol. 13, 27, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1186/s13229-022-00508-3\">10.1186/s13229-022-00508-3</a>.","ieee":"Z. A. Schaaf <i>et al.</i>, “WDFY3 mutation alters laminar position and morphology of cortical neurons,” <i>Molecular Autism</i>, vol. 13. Springer Nature, 2022.","ama":"Schaaf ZA, Tat L, Cannizzaro N, et al. WDFY3 mutation alters laminar position and morphology of cortical neurons. <i>Molecular Autism</i>. 2022;13. doi:<a href=\"https://doi.org/10.1186/s13229-022-00508-3\">10.1186/s13229-022-00508-3</a>","apa":"Schaaf, Z. A., Tat, L., Cannizzaro, N., Green, R., Rülicke, T., Hippenmeyer, S., &#38; Zarbalis, K. S. (2022). WDFY3 mutation alters laminar position and morphology of cortical neurons. <i>Molecular Autism</i>. Springer Nature. <a href=\"https://doi.org/10.1186/s13229-022-00508-3\">https://doi.org/10.1186/s13229-022-00508-3</a>","chicago":"Schaaf, Zachary A., Lyvin Tat, Noemi Cannizzaro, Ralph Green, Thomas Rülicke, Simon Hippenmeyer, and Konstantinos S. Zarbalis. “WDFY3 Mutation Alters Laminar Position and Morphology of Cortical Neurons.” <i>Molecular Autism</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1186/s13229-022-00508-3\">https://doi.org/10.1186/s13229-022-00508-3</a>.","ista":"Schaaf ZA, Tat L, Cannizzaro N, Green R, Rülicke T, Hippenmeyer S, Zarbalis KS. 2022. WDFY3 mutation alters laminar position and morphology of cortical neurons. Molecular Autism. 13, 27."},"related_material":{"link":[{"relation":"erratum","url":"https://doi.org/10.1186/s13229-023-00539-4"}]},"ddc":["570"],"doi":"10.1186/s13229-022-00508-3","article_type":"original"},{"ec_funded":1,"intvolume":"         3","file_date_updated":"2023-01-23T09:50:51Z","scopus_import":"1","publication":"STAR Protocols","author":[{"last_name":"Hübschmann","full_name":"Hübschmann, Verena","first_name":"Verena","id":"32B7C918-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Korkut, Medina","last_name":"Korkut","first_name":"Medina","id":"4B51CE74-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4309-2251"},{"first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","last_name":"Siegert","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877"}],"keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Neuroscience"],"publication_identifier":{"issn":["2666-1667"]},"oa":1,"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.","file":[{"file_size":6251945,"file_id":"12340","date_created":"2023-01-23T09:50:51Z","creator":"dernst","file_name":"2022_STARProtocols_Huebschmann.pdf","date_updated":"2023-01-23T09:50:51Z","checksum":"3c71b8a60633d42c2f77c49025d5559b","content_type":"application/pdf","success":1,"relation":"main_file","access_level":"open_access"}],"pmid":1,"language":[{"iso":"eng"}],"corr_author":"1","department":[{"_id":"SaSi"},{"_id":"GradSch"}],"external_id":{"pmid":["36595902"]},"date_created":"2023-01-12T11:56:38Z","publication_status":"published","acknowledged_ssus":[{"_id":"Bio"}],"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","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"}],"article_number":"101866","quality_controlled":"1","volume":3,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2022","oa_version":"Published Version","date_updated":"2025-06-11T13:58:47Z","project":[{"call_identifier":"H2020","name":"Microglia action towards neuronal circuit formation and function in health and disease","_id":"25D4A630-B435-11E9-9278-68D0E5697425","grant_number":"715571"},{"grant_number":"SC19-017","_id":"9B99D380-BA93-11EA-9121-9846C619BF3A","name":"How human microglia shape developing neurons during health and inflammation"}],"date_published":"2022-12-16T00:00:00Z","has_accepted_license":"1","day":"16","publisher":"Elsevier","type":"journal_article","issue":"4","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"status":"public","doi":"10.1016/j.xpro.2022.101866","article_type":"letter_note","ddc":["570"],"citation":{"ieee":"V. Hübschmann, M. Korkut, and S. Siegert, “Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay,” <i>STAR Protocols</i>, vol. 3, no. 4. Elsevier, 2022.","short":"V. Hübschmann, M. Korkut, S. Siegert, STAR Protocols 3 (2022).","mla":"Hübschmann, Verena, et al. “Assessing Human IPSC-Derived Microglia Identity and Function by Immunostaining, Phagocytosis, Calcium Activity, and Inflammation Assay.” <i>STAR Protocols</i>, vol. 3, no. 4, 101866, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.xpro.2022.101866\">10.1016/j.xpro.2022.101866</a>.","chicago":"Hübschmann, Verena, Medina Korkut, and Sandra Siegert. “Assessing Human IPSC-Derived Microglia Identity and Function by Immunostaining, Phagocytosis, Calcium Activity, and Inflammation Assay.” <i>STAR Protocols</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.xpro.2022.101866\">https://doi.org/10.1016/j.xpro.2022.101866</a>.","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.","ama":"Hübschmann V, Korkut M, Siegert S. Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay. <i>STAR Protocols</i>. 2022;3(4). doi:<a href=\"https://doi.org/10.1016/j.xpro.2022.101866\">10.1016/j.xpro.2022.101866</a>","apa":"Hübschmann, V., Korkut, M., &#38; Siegert, S. (2022). Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay. <i>STAR Protocols</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xpro.2022.101866\">https://doi.org/10.1016/j.xpro.2022.101866</a>"},"related_material":{"record":[{"relation":"other","status":"public","id":"11478"}]},"article_processing_charge":"No","title":"Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay","month":"12","_id":"12117"},{"publication":"Frontiers in Cellular Neuroscience","file_date_updated":"2023-01-24T09:16:29Z","author":[{"id":"36035796-5ACA-11E9-A75E-7AF2E5697425","first_name":"Bernadette","last_name":"Basilico","full_name":"Basilico, Bernadette","orcid":"0000-0003-1843-3173"},{"last_name":"Ferrucci","full_name":"Ferrucci, Laura","first_name":"Laura"},{"first_name":"Azka","full_name":"Khan, Azka","last_name":"Khan"},{"last_name":"Di Angelantonio","full_name":"Di Angelantonio, Silvia","first_name":"Silvia"},{"first_name":"Davide","last_name":"Ragozzino","full_name":"Ragozzino, Davide"},{"last_name":"Reverte","full_name":"Reverte, Ingrid","first_name":"Ingrid"}],"scopus_import":"1","keyword":["Cellular and Molecular Neuroscience"],"isi":1,"intvolume":"        16","file":[{"relation":"main_file","access_level":"open_access","success":1,"content_type":"application/pdf","checksum":"84696213ecf99182c58a9f34b9ff2e23","date_updated":"2023-01-24T09:16:29Z","file_id":"12352","date_created":"2023-01-24T09:16:29Z","file_name":"2022_FrontiersNeuroscience_Basilico.pdf","creator":"dernst","file_size":6399987}],"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).","pmid":1,"publication_identifier":{"issn":["1662-5102"]},"oa":1,"department":[{"_id":"GaNo"}],"external_id":{"isi":["000886526600001"],"pmid":["36406752"]},"date_created":"2023-01-12T12:04:50Z","language":[{"iso":"eng"}],"publication_status":"published","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."}],"article_number":"1022431","volume":16,"quality_controlled":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","has_accepted_license":"1","date_published":"2022-11-04T00:00:00Z","year":"2022","oa_version":"Published Version","date_updated":"2023-08-04T08:56:10Z","type":"journal_article","publisher":"Frontiers Media","day":"04","status":"public","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"doi":"10.3389/fncel.2022.1022431","article_type":"original","ddc":["570"],"article_processing_charge":"No","citation":{"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.","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.” <i>Frontiers in Cellular Neuroscience</i>. Frontiers Media, 2022. <a href=\"https://doi.org/10.3389/fncel.2022.1022431\">https://doi.org/10.3389/fncel.2022.1022431</a>.","apa":"Basilico, B., Ferrucci, L., Khan, A., Di Angelantonio, S., Ragozzino, D., &#38; Reverte, I. (2022). What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior. <i>Frontiers in Cellular Neuroscience</i>. Frontiers Media. <a href=\"https://doi.org/10.3389/fncel.2022.1022431\">https://doi.org/10.3389/fncel.2022.1022431</a>","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. <i>Frontiers in Cellular Neuroscience</i>. 2022;16. doi:<a href=\"https://doi.org/10.3389/fncel.2022.1022431\">10.3389/fncel.2022.1022431</a>","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,” <i>Frontiers in Cellular Neuroscience</i>, vol. 16. Frontiers Media, 2022.","mla":"Basilico, Bernadette, et al. “What Microglia Depletion Approaches Tell Us about the Role of Microglia on Synaptic Function and Behavior.” <i>Frontiers in Cellular Neuroscience</i>, vol. 16, 1022431, Frontiers Media, 2022, doi:<a href=\"https://doi.org/10.3389/fncel.2022.1022431\">10.3389/fncel.2022.1022431</a>.","short":"B. Basilico, L. Ferrucci, A. Khan, S. Di Angelantonio, D. Ragozzino, I. Reverte, Frontiers in Cellular Neuroscience 16 (2022)."},"_id":"12140","title":"What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior","month":"11"},{"ddc":["570"],"article_type":"letter_note","doi":"10.3389/fncir.2022.1028154","_id":"12149","month":"10","title":"Editorial: Neuromodulatory ascending systems: Their influence at the microscopic and macroscopic levels","article_processing_charge":"No","citation":{"short":"G. Gambino, R. Bhik-Ghanie, G. Giglia, M.V. Puig, J.F. Ramirez Villegas, D. Zaldivar, Frontiers in Neural Circuits 16 (2022).","mla":"Gambino, Giuditta, et al. “Editorial: Neuromodulatory Ascending Systems: Their Influence at the Microscopic and Macroscopic Levels.” <i>Frontiers in Neural Circuits</i>, vol. 16, 1028154, Frontiers Media, 2022, doi:<a href=\"https://doi.org/10.3389/fncir.2022.1028154\">10.3389/fncir.2022.1028154</a>.","ieee":"G. Gambino, R. Bhik-Ghanie, G. Giglia, M. V. Puig, J. F. Ramirez Villegas, and D. Zaldivar, “Editorial: Neuromodulatory ascending systems: Their influence at the microscopic and macroscopic levels,” <i>Frontiers in Neural Circuits</i>, vol. 16. Frontiers Media, 2022.","apa":"Gambino, G., Bhik-Ghanie, R., Giglia, G., Puig, M. V., Ramirez Villegas, J. F., &#38; Zaldivar, D. (2022). Editorial: Neuromodulatory ascending systems: Their influence at the microscopic and macroscopic levels. <i>Frontiers in Neural Circuits</i>. Frontiers Media. <a href=\"https://doi.org/10.3389/fncir.2022.1028154\">https://doi.org/10.3389/fncir.2022.1028154</a>","ama":"Gambino G, Bhik-Ghanie R, Giglia G, Puig MV, Ramirez Villegas JF, Zaldivar D. Editorial: Neuromodulatory ascending systems: Their influence at the microscopic and macroscopic levels. <i>Frontiers in Neural Circuits</i>. 2022;16. doi:<a href=\"https://doi.org/10.3389/fncir.2022.1028154\">10.3389/fncir.2022.1028154</a>","ista":"Gambino G, Bhik-Ghanie R, Giglia G, Puig MV, Ramirez Villegas JF, Zaldivar D. 2022. Editorial: Neuromodulatory ascending systems: Their influence at the microscopic and macroscopic levels. Frontiers in Neural Circuits. 16, 1028154.","chicago":"Gambino, Giuditta, Rebecca Bhik-Ghanie, Giuseppe Giglia, M. Victoria Puig, Juan F Ramirez Villegas, and Daniel Zaldivar. “Editorial: Neuromodulatory Ascending Systems: Their Influence at the Microscopic and Macroscopic Levels.” <i>Frontiers in Neural Circuits</i>. Frontiers Media, 2022. <a href=\"https://doi.org/10.3389/fncir.2022.1028154\">https://doi.org/10.3389/fncir.2022.1028154</a>."},"date_published":"2022-10-26T00:00:00Z","has_accepted_license":"1","project":[{"name":"The Brainstem-Hippocampus Network Uncovered: Dynamics, Reactivation and Memory Consolidation","call_identifier":"H2020","grant_number":"841301","_id":"26BAE2E4-B435-11E9-9278-68D0E5697425"}],"date_updated":"2025-06-12T06:19:09Z","oa_version":"Published Version","year":"2022","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"publisher":"Frontiers Media","type":"journal_article","day":"26","publication_status":"published","date_created":"2023-01-12T12:07:39Z","external_id":{"pmid":["36405671"],"isi":["000886671400001"]},"department":[{"_id":"JoCs"}],"language":[{"iso":"eng"}],"volume":16,"quality_controlled":"1","article_number":"1028154","abstract":[{"text":"Editorial on the Research Topic","lang":"eng"}],"scopus_import":"1","keyword":["Cellular and Molecular Neuroscience","Cognitive Neuroscience","Sensory Systems","Neuroscience (miscellaneous)"],"file_date_updated":"2023-01-24T10:10:43Z","author":[{"first_name":"Giuditta","last_name":"Gambino","full_name":"Gambino, Giuditta"},{"full_name":"Bhik-Ghanie, Rebecca","last_name":"Bhik-Ghanie","first_name":"Rebecca"},{"first_name":"Giuseppe","full_name":"Giglia, Giuseppe","last_name":"Giglia"},{"last_name":"Puig","full_name":"Puig, M. Victoria","first_name":"M. Victoria"},{"full_name":"Ramirez Villegas, Juan F","last_name":"Ramirez Villegas","id":"44B06F76-F248-11E8-B48F-1D18A9856A87","first_name":"Juan F"},{"first_name":"Daniel","last_name":"Zaldivar","full_name":"Zaldivar, Daniel"}],"publication":"Frontiers in Neural Circuits","isi":1,"intvolume":"        16","ec_funded":1,"pmid":1,"file":[{"access_level":"open_access","relation":"main_file","success":1,"checksum":"457aa00e1800847abb340853058531de","content_type":"application/pdf","date_updated":"2023-01-24T10:10:43Z","creator":"dernst","file_name":"2022_FrontiersNeuralCircuits_Gambino.pdf","file_id":"12357","date_created":"2023-01-24T10:10:43Z","file_size":110031}],"acknowledgement":"This work was supported by a DFG grant ZA990/1 to DZ. This work was supported by the MSCA EU proposal 841301 - DREAM, European Commission; Horizon 2020 - Research and Innovation Framework Programme to JFRV.","oa":1,"publication_identifier":{"issn":["1662-5110"]}},{"article_processing_charge":"No","citation":{"ista":"Jiang X, Harker-Kirschneck L, Vanhille-Campos CE, Pfitzner A-K, Lominadze E, Roux A, Baum B, Šarić A. 2022. Modelling membrane reshaping by staged polymerization of ESCRT-III filaments. PLOS Computational Biology. 18(10), e1010586.","chicago":"Jiang, Xiuyun, Lena Harker-Kirschneck, Christian Eduardo Vanhille-Campos, Anna-Katharina Pfitzner, Elene Lominadze, Aurélien Roux, Buzz Baum, and Anđela Šarić. “Modelling Membrane Reshaping by Staged Polymerization of ESCRT-III Filaments.” <i>PLOS Computational Biology</i>. Public Library of Science, 2022. <a href=\"https://doi.org/10.1371/journal.pcbi.1010586\">https://doi.org/10.1371/journal.pcbi.1010586</a>.","apa":"Jiang, X., Harker-Kirschneck, L., Vanhille-Campos, C. E., Pfitzner, A.-K., Lominadze, E., Roux, A., … Šarić, A. (2022). Modelling membrane reshaping by staged polymerization of ESCRT-III filaments. <i>PLOS Computational Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1010586\">https://doi.org/10.1371/journal.pcbi.1010586</a>","ama":"Jiang X, Harker-Kirschneck L, Vanhille-Campos CE, et al. Modelling membrane reshaping by staged polymerization of ESCRT-III filaments. <i>PLOS Computational Biology</i>. 2022;18(10). doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1010586\">10.1371/journal.pcbi.1010586</a>","ieee":"X. Jiang <i>et al.</i>, “Modelling membrane reshaping by staged polymerization of ESCRT-III filaments,” <i>PLOS Computational Biology</i>, vol. 18, no. 10. Public Library of Science, 2022.","mla":"Jiang, Xiuyun, et al. “Modelling Membrane Reshaping by Staged Polymerization of ESCRT-III Filaments.” <i>PLOS Computational Biology</i>, vol. 18, no. 10, e1010586, Public Library of Science, 2022, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1010586\">10.1371/journal.pcbi.1010586</a>.","short":"X. Jiang, L. Harker-Kirschneck, C.E. Vanhille-Campos, A.-K. Pfitzner, E. Lominadze, A. Roux, B. Baum, A. Šarić, PLOS Computational Biology 18 (2022)."},"related_material":{"link":[{"relation":"software","url":"https://github.com/sharonJXY/3-filament-model"}]},"_id":"12152","title":"Modelling membrane reshaping by staged polymerization of ESCRT-III filaments","month":"10","doi":"10.1371/journal.pcbi.1010586","article_type":"original","ddc":["570"],"publisher":"Public Library of Science","type":"journal_article","day":"17","issue":"10","status":"public","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","project":[{"grant_number":"802960","_id":"eba2549b-77a9-11ec-83b8-a81e493eae4e","name":"Non-Equilibrium Protein Assembly: from Building Blocks to Biological Machines","call_identifier":"H2020"},{"_id":"eba0f67c-77a9-11ec-83b8-cc8501b3e222","grant_number":"96752","name":"The evolution of trafficking: from archaea to eukaryotes"}],"has_accepted_license":"1","date_published":"2022-10-17T00:00:00Z","oa_version":"Published Version","year":"2022","date_updated":"2025-06-12T06:19:28Z","abstract":[{"lang":"eng","text":"ESCRT-III filaments are composite cytoskeletal polymers that can constrict and cut cell membranes from the inside of the membrane neck. Membrane-bound ESCRT-III filaments undergo a series of dramatic composition and geometry changes in the presence of an ATP-consuming Vps4 enzyme, which causes stepwise changes in the membrane morphology. We set out to understand the physical mechanisms involved in translating the changes in ESCRT-III polymer composition into membrane deformation. We have built a coarse-grained model in which ESCRT-III polymers of different geometries and mechanical properties are allowed to copolymerise and bind to a deformable membrane. By modelling ATP-driven stepwise depolymerisation of specific polymers, we identify mechanical regimes in which changes in filament composition trigger the associated membrane transition from a flat to a buckled state, and then to a tubule state that eventually undergoes scission to release a small cargo-loaded vesicle. We then characterise how the location and kinetics of polymer loss affects the extent of membrane deformation and the efficiency of membrane neck scission. Our results identify the near-minimal mechanical conditions for the operation of shape-shifting composite polymers that sever membrane necks."}],"article_number":"e1010586","volume":18,"quality_controlled":"1","external_id":{"isi":["000924885500005"],"pmid":["36251703"]},"department":[{"_id":"AnSa"}],"date_created":"2023-01-12T12:08:10Z","corr_author":"1","language":[{"iso":"eng"}],"publication_status":"published","file":[{"success":1,"relation":"main_file","access_level":"open_access","file_size":2641067,"date_created":"2023-01-24T10:45:01Z","file_id":"12359","file_name":"2022_PLoSCompBio_Jiang.pdf","creator":"dernst","date_updated":"2023-01-24T10:45:01Z","checksum":"bada6a7865e470cf42bbdfa67dd471d2","content_type":"application/pdf"}],"acknowledgement":"A.S . received an award from European Research Council (https://erc.europa.eu, “NEPA\"\r\n802960), and an award from the Royal Society (https://royalsociety.org, UF160266). L. H.-K.\r\nreceived an award from the Biotechnology and Biological Sciences Research Council (https://\r\nwww.ukri.org/councils/bbsrc/). E. L. received an award from the University College London (https://www.ucl.ac.uk/biophysics/news/2022/feb/applications-biop-brian-duff-and-ipls-summerundergraduate-studentships-now-open, Brian Duff Undergraduate Summer Research Studentship). B.B. and A.S. received an award from Volkswagen Foundation https://www.volkswagenstiftung.de/en/foundation, Az 96727), and an award from Medical Research Council (https://www.ukri.org/councils/mrc, MC_CF1226). A. R. received an\r\naward from the Swiss National Fund for Research (https://www.snf.ch/en, 31003A_130520,\r\n31003A_149975, and 31003A_173087) and an award from the European Research Council\r\nConsolidator (https://erc.europa.eu, 311536). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","pmid":1,"oa":1,"publication_identifier":{"issn":["1553-7358"]},"keyword":["Computational Theory and Mathematics","Cellular and Molecular Neuroscience","Genetics","Molecular Biology","Ecology","Modeling and Simulation","Ecology","Evolution","Behavior and Systematics"],"scopus_import":"1","author":[{"last_name":"Jiang","full_name":"Jiang, Xiuyun","first_name":"Xiuyun"},{"last_name":"Harker-Kirschneck","full_name":"Harker-Kirschneck, Lena","first_name":"Lena"},{"id":"3adeca52-9313-11ed-b1ac-c170b2505714","first_name":"Christian Eduardo","full_name":"Vanhille-Campos, Christian Eduardo","last_name":"Vanhille-Campos"},{"last_name":"Pfitzner","full_name":"Pfitzner, Anna-Katharina","first_name":"Anna-Katharina"},{"first_name":"Elene","full_name":"Lominadze, Elene","last_name":"Lominadze"},{"first_name":"Aurélien","last_name":"Roux","full_name":"Roux, Aurélien"},{"last_name":"Baum","full_name":"Baum, Buzz","first_name":"Buzz"},{"full_name":"Šarić, Anđela","last_name":"Šarić","id":"bf63d406-f056-11eb-b41d-f263a6566d8b","first_name":"Anđela","orcid":"0000-0002-7854-2139"}],"publication":"PLOS Computational Biology","file_date_updated":"2023-01-24T10:45:01Z","ec_funded":1,"isi":1,"intvolume":"        18"},{"article_processing_charge":"No","citation":{"mla":"Hayward, Laura, and Guy Sella. “Polygenic Adaptation after a Sudden Change in Environment.” <i>ELife</i>, vol. 11, 66697, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/elife.66697\">10.7554/elife.66697</a>.","short":"L. Hayward, G. Sella, ELife 11 (2022).","ieee":"L. Hayward and G. Sella, “Polygenic adaptation after a sudden change in environment,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","apa":"Hayward, L., &#38; Sella, G. (2022). Polygenic adaptation after a sudden change in environment. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.66697\">https://doi.org/10.7554/elife.66697</a>","ama":"Hayward L, Sella G. Polygenic adaptation after a sudden change in environment. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/elife.66697\">10.7554/elife.66697</a>","ista":"Hayward L, Sella G. 2022. Polygenic adaptation after a sudden change in environment. eLife. 11, 66697.","chicago":"Hayward, Laura, and Guy Sella. “Polygenic Adaptation after a Sudden Change in Environment.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/elife.66697\">https://doi.org/10.7554/elife.66697</a>."},"_id":"12157","month":"09","title":"Polygenic adaptation after a sudden change in environment","article_type":"original","doi":"10.7554/elife.66697","ddc":["570"],"publisher":"eLife Sciences Publications","day":"26","type":"journal_article","status":"public","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","date_published":"2022-09-26T00:00:00Z","has_accepted_license":"1","date_updated":"2024-10-09T21:03:38Z","year":"2022","oa_version":"Published Version","article_number":"66697","abstract":[{"lang":"eng","text":"Polygenic adaptation is thought to be ubiquitous, yet remains poorly understood. Here, we model this process analytically, in the plausible setting of a highly polygenic, quantitative trait that experiences a sudden shift in the fitness optimum. We show how the mean phenotype changes over time, depending on the effect sizes of loci that contribute to variance in the trait, and characterize the allele dynamics at these loci. Notably, we describe the two phases of the allele dynamics: The first is a rapid phase, in which directional selection introduces small frequency differences between alleles whose effects are aligned with or opposed to the shift, ultimately leading to small differences in their probability of fixation during a second, longer phase, governed by stabilizing selection. As we discuss, key results should hold in more general settings and have important implications for efforts to identify the genetic basis of adaptation in humans and other species."}],"volume":11,"quality_controlled":"1","date_created":"2023-01-12T12:09:00Z","external_id":{"isi":["000890735600001"]},"department":[{"_id":"NiBa"}],"corr_author":"1","language":[{"iso":"eng"}],"publication_status":"published","acknowledgement":"We thank Guy Amster, Jeremy Berg, Nick Barton, Yuval Simons and Molly Przeworski for many helpful discussions, and Jeremy Berg, Graham Coop, Joachim Hermisson, Guillaume Martin, Will Milligan, Peter Ralph, Yuval Simons, Leo Speidel and Molly Przeworski for comments on the manuscript.\r\nNational Institutes of Health GM115889 Laura Katharine Hayward Guy Sella \r\nNational Institutes of Health GM121372 Laura Katharine Hayward","file":[{"file_size":18935612,"file_name":"2022_eLife_Hayward.pdf","creator":"dernst","date_created":"2023-01-24T12:21:32Z","file_id":"12363","date_updated":"2023-01-24T12:21:32Z","checksum":"28de155b231ac1c8d4501c98b2fb359a","content_type":"application/pdf","success":1,"access_level":"open_access","relation":"main_file"}],"publication_identifier":{"eissn":["2050-084X"]},"oa":1,"keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"author":[{"first_name":"Laura","id":"fc885ee5-24bf-11eb-ad7b-bcc5104c0c1b","full_name":"Hayward, Laura","last_name":"Hayward"},{"last_name":"Sella","full_name":"Sella, Guy","first_name":"Guy"}],"scopus_import":"1","publication":"eLife","file_date_updated":"2023-01-24T12:21:32Z","isi":1,"intvolume":"        11"},{"title":"Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice","month":"09","_id":"12212","citation":{"ieee":"A. Martín-Belmonte <i>et al.</i>, “Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice,” <i>Alzheimer’s Research &#38; Therapy</i>, vol. 14. Springer Nature, 2022.","mla":"Martín-Belmonte, Alejandro, et al. “Nanoscale Alterations in GABAB Receptors and GIRK Channel Organization on the Hippocampus of APP/PS1 Mice.” <i>Alzheimer’s Research &#38; Therapy</i>, vol. 14, 136, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1186/s13195-022-01078-5\">10.1186/s13195-022-01078-5</a>.","short":"A. Martín-Belmonte, C. Aguado, R. Alfaro-Ruiz, A.E. Moreno-Martínez, L. de la Ossa, E. Aso, L. Gómez-Acero, R. Shigemoto, Y. Fukazawa, F. Ciruela, R. Luján, Alzheimer’s Research &#38; Therapy 14 (2022).","chicago":"Martín-Belmonte, Alejandro, Carolina Aguado, Rocío Alfaro-Ruiz, Ana Esther Moreno-Martínez, Luis de la Ossa, Ester Aso, Laura Gómez-Acero, et al. “Nanoscale Alterations in GABAB Receptors and GIRK Channel Organization on the Hippocampus of APP/PS1 Mice.” <i>Alzheimer’s Research &#38; Therapy</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1186/s13195-022-01078-5\">https://doi.org/10.1186/s13195-022-01078-5</a>.","ista":"Martín-Belmonte A, Aguado C, Alfaro-Ruiz R, Moreno-Martínez AE, de la Ossa L, Aso E, Gómez-Acero L, Shigemoto R, Fukazawa Y, Ciruela F, Luján R. 2022. Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice. Alzheimer’s Research &#38; Therapy. 14, 136.","ama":"Martín-Belmonte A, Aguado C, Alfaro-Ruiz R, et al. Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice. <i>Alzheimer’s Research &#38; Therapy</i>. 2022;14. doi:<a href=\"https://doi.org/10.1186/s13195-022-01078-5\">10.1186/s13195-022-01078-5</a>","apa":"Martín-Belmonte, A., Aguado, C., Alfaro-Ruiz, R., Moreno-Martínez, A. E., de la Ossa, L., Aso, E., … Luján, R. (2022). Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice. <i>Alzheimer’s Research &#38; Therapy</i>. Springer Nature. <a href=\"https://doi.org/10.1186/s13195-022-01078-5\">https://doi.org/10.1186/s13195-022-01078-5</a>"},"article_processing_charge":"No","ddc":["570"],"doi":"10.1186/s13195-022-01078-5","article_type":"original","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"status":"public","publisher":"Springer Nature","day":"21","type":"journal_article","year":"2022","oa_version":"Published Version","date_updated":"2025-06-11T13:40:00Z","has_accepted_license":"1","date_published":"2022-09-21T00:00:00Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","quality_controlled":"1","volume":14,"abstract":[{"text":"Alzheimer’s disease (AD) is characterized by a reorganization of brain activity determining network hyperexcitability and loss of synaptic plasticity. Precisely, a dysfunction in metabotropic GABAB receptor signalling through G protein-gated inwardly rectifying K+ (GIRK or Kir3) channels on the hippocampus has been postulated. Thus, we determined the impact of amyloid-β (Aβ) pathology in GIRK channel density, subcellular distribution, and its association with GABAB receptors in hippocampal CA1 pyramidal neurons from the APP/PS1 mouse model using quantitative SDS-digested freeze-fracture replica labelling (SDS-FRL) and proximity ligation in situ assay (P-LISA). In wild type mice, single SDS-FRL detection revealed a similar dendritic gradient for GIRK1 and GIRK2 in CA1 pyramidal cells, with higher densities in spines, and GIRK3 showed a lower and uniform distribution. Double SDS-FRL showed a co-clustering of GIRK2 and GIRK1 in post- and presynaptic compartments, but not for GIRK2 and GIRK3. Likewise, double GABAB1 and GIRK2 SDS-FRL detection displayed a high degree of co-clustering in nanodomains (40–50 nm) mostly in spines and axon terminals. In APP/PS1 mice, the density of GIRK2 and GIRK1, but not for GIRK3, was significantly reduced along the neuronal surface of CA1 pyramidal cells and in axon terminals contacting them. Importantly, GABAB1 and GIRK2 co-clustering was not present in APP/PS1 mice. Similarly, P-LISA experiments revealed a significant reduction in GABAB1 and GIRK2 interaction on the hippocampus of this animal model. Overall, our results provide compelling evidence showing a significant reduction on the cell surface density of pre- and postsynaptic GIRK1 and GIRK2, but not GIRK3, and a decline in GABAB receptors and GIRK2 channels co-clustering in hippocampal pyramidal neurons from APP/PS1 mice, thus suggesting that a disruption in the GABAB receptor–GIRK channel membrane assembly causes dysregulation in the GABAB signalling via GIRK channels in this AD animal model.","lang":"eng"}],"article_number":"136","publication_status":"published","language":[{"iso":"eng"}],"external_id":{"pmid":["36131327"],"isi":["000857985500001"]},"department":[{"_id":"RySh"}],"date_created":"2023-01-16T09:45:51Z","oa":1,"publication_identifier":{"issn":["1758-9193"]},"file":[{"relation":"main_file","access_level":"open_access","success":1,"checksum":"88e49715ad6a1abf0fdb27efd65368dc","content_type":"application/pdf","date_updated":"2023-01-27T07:53:18Z","file_id":"12413","date_created":"2023-01-27T07:53:18Z","file_name":"2022_AlzheimersResearch_MartinBelmont.pdf","creator":"dernst","file_size":11013325}],"acknowledgement":"We thank Ms. Diane Latawiec for the English revision of the manuscript. Funding sources were the Spanish Ministerio de Economía y Competitividad, Junta de Comunidades de Castilla-La Mancha (Spain), and Life Science Innovation Center at University of Fukui. We thank Centres de Recerca de Catalunya (CERCA) Programme/Generalitat de Catalunya for IDIBELL institutional support. We thank Hitoshi Takagi and Takako Maegawa at the University of Fukui for their technical assistance on SDS-FRL experiments.\r\nThis work was supported by grants from the Spanish Ministerio de Economía y Competitividad (BFU2015-63769-R, RTI2018-095812-B-I00, and PID2021-125875OB-I00) and Junta de Comunidades de Castilla-La Mancha (SBPLY/17/180501/000229 and SBPLY/21/180501/000064) to RL, Life Science Innovation Center at University of Fukui and JSPS KAKENHI (Grant Numbers 16H04662, 19H03323, and 20H05058) to YF, and Margarita Salas fellowship from Ministerio de Universidades and Universidad de Castilla-La Mancha to AMB.","pmid":1,"isi":1,"intvolume":"        14","file_date_updated":"2023-01-27T07:53:18Z","scopus_import":"1","publication":"Alzheimer's Research & Therapy","keyword":["Cognitive Neuroscience","Neurology (clinical)","Neurology"],"author":[{"full_name":"Martín-Belmonte, Alejandro","last_name":"Martín-Belmonte","first_name":"Alejandro"},{"first_name":"Carolina","full_name":"Aguado, Carolina","last_name":"Aguado"},{"first_name":"Rocío","full_name":"Alfaro-Ruiz, Rocío","last_name":"Alfaro-Ruiz"},{"last_name":"Moreno-Martínez","full_name":"Moreno-Martínez, Ana Esther","first_name":"Ana Esther"},{"last_name":"de la Ossa","full_name":"de la Ossa, Luis","first_name":"Luis"},{"first_name":"Ester","last_name":"Aso","full_name":"Aso, Ester"},{"last_name":"Gómez-Acero","full_name":"Gómez-Acero, Laura","first_name":"Laura"},{"orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","first_name":"Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Yugo","last_name":"Fukazawa","full_name":"Fukazawa, Yugo"},{"full_name":"Ciruela, Francisco","last_name":"Ciruela","first_name":"Francisco"},{"last_name":"Luján","full_name":"Luján, Rafael","first_name":"Rafael"}]},{"isi":1,"intvolume":"        16","publication":"Frontiers in Neuroscience","file_date_updated":"2023-01-30T09:15:13Z","scopus_import":"1","author":[{"first_name":"Tanja","last_name":"Weiffert","full_name":"Weiffert, Tanja"},{"first_name":"Georg","full_name":"Meisl, Georg","last_name":"Meisl"},{"first_name":"Samo","last_name":"Curk","full_name":"Curk, Samo"},{"first_name":"Risto","last_name":"Cukalevski","full_name":"Cukalevski, Risto"},{"full_name":"Šarić, Anđela","last_name":"Šarić","first_name":"Anđela","id":"bf63d406-f056-11eb-b41d-f263a6566d8b","orcid":"0000-0002-7854-2139"},{"first_name":"Tuomas P. J.","last_name":"Knowles","full_name":"Knowles, Tuomas P. J."},{"full_name":"Linse, Sara","last_name":"Linse","first_name":"Sara"}],"keyword":["General Neuroscience"],"publication_identifier":{"issn":["1662-453X"]},"oa":1,"file":[{"date_updated":"2023-01-30T09:15:13Z","checksum":"e67d16113ffb4fb4fa38a183d169f210","content_type":"application/pdf","file_size":19798610,"date_created":"2023-01-30T09:15:13Z","file_id":"12442","file_name":"2022_FrontiersNeuroscience_Weiffert2.pdf","creator":"dernst","relation":"main_file","access_level":"open_access","success":1}],"acknowledgement":"This work was supported by grants from the Swedish Research Council (grant no. 2015-00143) and the European Research Council (grant no. 340890).","language":[{"iso":"eng"}],"external_id":{"isi":["000866287100001"]},"department":[{"_id":"AnSa"}],"date_created":"2023-01-16T09:56:43Z","publication_status":"published","abstract":[{"text":"Amyloid formation is linked to devastating neurodegenerative diseases, motivating detailed studies of the mechanisms of amyloid formation. For Aβ, the peptide associated with Alzheimer’s disease, the mechanism and rate of aggregation have been established for a range of variants and conditions <jats:italic>in vitro</jats:italic> and in bodily fluids. A key outstanding question is how the relative stabilities of monomers, fibrils and intermediates affect each step in the fibril formation process. By monitoring the kinetics of aggregation of Aβ42, in the presence of urea or guanidinium hydrochloride (GuHCl), we here determine the rates of the underlying microscopic steps and establish the importance of changes in relative stability induced by the presence of denaturant for each individual step. Denaturants shift the equilibrium towards the unfolded state of each species. We find that a non-ionic denaturant, urea, reduces the overall aggregation rate, and that the effect on nucleation is stronger than the effect on elongation. Urea reduces the rate of secondary nucleation by decreasing the coverage of fibril surfaces and the rate of nucleus formation. It also reduces the rate of primary nucleation, increasing its reaction order. The ionic denaturant, GuHCl, accelerates the aggregation at low denaturant concentrations and decelerates the aggregation at high denaturant concentrations. Below approximately 0.25 M GuHCl, the screening of repulsive electrostatic interactions between peptides by the charged denaturant dominates, leading to an increased aggregation rate. At higher GuHCl concentrations, the electrostatic repulsion is completely screened, and the denaturing effect dominates. The results illustrate how the differential effects of denaturants on stability of monomer, oligomer and fibril translate to differential effects on microscopic steps, with the rate of nucleation being most strongly reduced.","lang":"eng"}],"article_number":"943355","quality_controlled":"1","volume":16,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"Published Version","year":"2022","date_updated":"2023-08-04T09:48:56Z","has_accepted_license":"1","date_published":"2022-09-20T00:00:00Z","type":"journal_article","publisher":"Frontiers Media","day":"20","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"status":"public","doi":"10.3389/fnins.2022.943355","article_type":"original","ddc":["570"],"citation":{"ama":"Weiffert T, Meisl G, Curk S, et al. Influence of denaturants on amyloid β42 aggregation kinetics. <i>Frontiers in Neuroscience</i>. 2022;16. doi:<a href=\"https://doi.org/10.3389/fnins.2022.943355\">10.3389/fnins.2022.943355</a>","apa":"Weiffert, T., Meisl, G., Curk, S., Cukalevski, R., Šarić, A., Knowles, T. P. J., &#38; Linse, S. (2022). Influence of denaturants on amyloid β42 aggregation kinetics. <i>Frontiers in Neuroscience</i>. Frontiers Media. <a href=\"https://doi.org/10.3389/fnins.2022.943355\">https://doi.org/10.3389/fnins.2022.943355</a>","chicago":"Weiffert, Tanja, Georg Meisl, Samo Curk, Risto Cukalevski, Anđela Šarić, Tuomas P. J. Knowles, and Sara Linse. “Influence of Denaturants on Amyloid Β42 Aggregation Kinetics.” <i>Frontiers in Neuroscience</i>. Frontiers Media, 2022. <a href=\"https://doi.org/10.3389/fnins.2022.943355\">https://doi.org/10.3389/fnins.2022.943355</a>.","ista":"Weiffert T, Meisl G, Curk S, Cukalevski R, Šarić A, Knowles TPJ, Linse S. 2022. Influence of denaturants on amyloid β42 aggregation kinetics. Frontiers in Neuroscience. 16, 943355.","short":"T. Weiffert, G. Meisl, S. Curk, R. Cukalevski, A. Šarić, T.P.J. Knowles, S. Linse, Frontiers in Neuroscience 16 (2022).","mla":"Weiffert, Tanja, et al. “Influence of Denaturants on Amyloid Β42 Aggregation Kinetics.” <i>Frontiers in Neuroscience</i>, vol. 16, 943355, Frontiers Media, 2022, doi:<a href=\"https://doi.org/10.3389/fnins.2022.943355\">10.3389/fnins.2022.943355</a>.","ieee":"T. Weiffert <i>et al.</i>, “Influence of denaturants on amyloid β42 aggregation kinetics,” <i>Frontiers in Neuroscience</i>, vol. 16. Frontiers Media, 2022."},"article_processing_charge":"No","title":"Influence of denaturants on amyloid β42 aggregation kinetics","month":"09","_id":"12251"},{"issue":"6","type":"journal_article","day":"14","publisher":"Public Library of Science","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","date_updated":"2025-04-14T07:52:47Z","oa_version":"Published Version","year":"2022","date_published":"2022-06-14T00:00:00Z","project":[{"grant_number":"863818","_id":"0599E47C-7A3F-11EA-A408-12923DDC885E","call_identifier":"H2020","name":"Formal Methods for Stochastic Models: Algorithms and Applications"}],"has_accepted_license":"1","citation":{"ista":"Schmid L, Hilbe C, Chatterjee K, Nowak M. 2022. Direct reciprocity between individuals that use different strategy spaces. PLOS Computational Biology. 18(6), e1010149.","chicago":"Schmid, Laura, Christian Hilbe, Krishnendu Chatterjee, and Martin Nowak. “Direct Reciprocity between Individuals That Use Different Strategy Spaces.” <i>PLOS Computational Biology</i>. Public Library of Science, 2022. <a href=\"https://doi.org/10.1371/journal.pcbi.1010149\">https://doi.org/10.1371/journal.pcbi.1010149</a>.","apa":"Schmid, L., Hilbe, C., Chatterjee, K., &#38; Nowak, M. (2022). Direct reciprocity between individuals that use different strategy spaces. <i>PLOS Computational Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1010149\">https://doi.org/10.1371/journal.pcbi.1010149</a>","ama":"Schmid L, Hilbe C, Chatterjee K, Nowak M. Direct reciprocity between individuals that use different strategy spaces. <i>PLOS Computational Biology</i>. 2022;18(6). doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1010149\">10.1371/journal.pcbi.1010149</a>","ieee":"L. Schmid, C. Hilbe, K. Chatterjee, and M. Nowak, “Direct reciprocity between individuals that use different strategy spaces,” <i>PLOS Computational Biology</i>, vol. 18, no. 6. Public Library of Science, 2022.","short":"L. Schmid, C. Hilbe, K. Chatterjee, M. Nowak, PLOS Computational Biology 18 (2022).","mla":"Schmid, Laura, et al. “Direct Reciprocity between Individuals That Use Different Strategy Spaces.” <i>PLOS Computational Biology</i>, vol. 18, no. 6, e1010149, Public Library of Science, 2022, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1010149\">10.1371/journal.pcbi.1010149</a>."},"article_processing_charge":"No","month":"06","title":"Direct reciprocity between individuals that use different strategy spaces","_id":"12280","article_type":"original","doi":"10.1371/journal.pcbi.1010149","ddc":["000","570"],"oa":1,"publication_identifier":{"eissn":["1553-7358"]},"pmid":1,"file":[{"relation":"main_file","access_level":"open_access","success":1,"date_updated":"2023-01-30T11:28:13Z","checksum":"31b6b311b6731f1658277a9dfff6632c","content_type":"application/pdf","file_size":3143222,"date_created":"2023-01-30T11:28:13Z","file_id":"12460","file_name":"2022_PlosCompBio_Schmid.pdf","creator":"dernst"}],"acknowledgement":"This work was supported by the European Research Council (https://erc.europa.eu/)\r\nCoG 863818 (ForM-SMArt) (to K.C.), and the European Research Council Starting Grant 850529: E-DIRECT (to C.H.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","intvolume":"        18","isi":1,"ec_funded":1,"file_date_updated":"2023-01-30T11:28:13Z","keyword":["Computational Theory and Mathematics","Cellular and Molecular Neuroscience","Genetics","Molecular Biology","Ecology","Modeling and Simulation","Ecology","Evolution","Behavior and Systematics"],"publication":"PLOS Computational Biology","scopus_import":"1","author":[{"orcid":"0000-0002-6978-7329","first_name":"Laura","id":"38B437DE-F248-11E8-B48F-1D18A9856A87","last_name":"Schmid","full_name":"Schmid, Laura"},{"id":"2FDF8F3C-F248-11E8-B48F-1D18A9856A87","first_name":"Christian","full_name":"Hilbe, Christian","last_name":"Hilbe","orcid":"0000-0001-5116-955X"},{"last_name":"Chatterjee","full_name":"Chatterjee, Krishnendu","first_name":"Krishnendu","id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4561-241X"},{"full_name":"Nowak, Martin","last_name":"Nowak","first_name":"Martin"}],"article_number":"e1010149","abstract":[{"lang":"eng","text":"In repeated interactions, players can use strategies that respond to the outcome of previous rounds. Much of the existing literature on direct reciprocity assumes that all competing individuals use the same strategy space. Here, we study both learning and evolutionary dynamics of players that differ in the strategy space they explore. We focus on the infinitely repeated donation game and compare three natural strategy spaces: memory-1 strategies, which consider the last moves of both players, reactive strategies, which respond to the last move of the co-player, and unconditional strategies. These three strategy spaces differ in the memory capacity that is needed. We compute the long term average payoff that is achieved in a pairwise learning process. We find that smaller strategy spaces can dominate larger ones. For weak selection, unconditional players dominate both reactive and memory-1 players. For intermediate selection, reactive players dominate memory-1 players. Only for strong selection and low cost-to-benefit ratio, memory-1 players dominate the others. We observe that the supergame between strategy spaces can be a social dilemma: maximum payoff is achieved if both players explore a larger strategy space, but smaller strategy spaces dominate."}],"quality_controlled":"1","volume":18,"language":[{"iso":"eng"}],"corr_author":"1","date_created":"2023-01-16T10:02:51Z","department":[{"_id":"KrCh"}],"external_id":{"isi":["000843626800031"],"pmid":["35700167"]},"publication_status":"published"},{"doi":"10.7554/elife.79848","article_type":"original","ddc":["570"],"citation":{"apa":"Sumser, A. L., Jösch, M. A., Jonas, P. M., &#38; Ben Simon, Y. (2022). Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.79848\">https://doi.org/10.7554/elife.79848</a>","ama":"Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/elife.79848\">10.7554/elife.79848</a>","ista":"Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. 2022. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. eLife. 11, 79848.","chicago":"Sumser, Anton L, Maximilian A Jösch, Peter M Jonas, and Yoav Ben Simon. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/elife.79848\">https://doi.org/10.7554/elife.79848</a>.","mla":"Sumser, Anton L., et al. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” <i>ELife</i>, vol. 11, 79848, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/elife.79848\">10.7554/elife.79848</a>.","short":"A.L. Sumser, M.A. Jösch, P.M. Jonas, Y. Ben Simon, ELife 11 (2022).","ieee":"A. L. Sumser, M. A. Jösch, P. M. Jonas, and Y. Ben Simon, “Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022."},"article_processing_charge":"No","title":"Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling","month":"09","_id":"12288","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"Published Version","year":"2022","date_updated":"2025-04-15T08:29:05Z","date_published":"2022-09-15T00:00:00Z","has_accepted_license":"1","project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","call_identifier":"H2020","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"grant_number":"756502","_id":"2634E9D2-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Circuits of Visual Attention"},{"call_identifier":"FWF","name":"Synaptic communication in neuronal microcircuits","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"name":"Neuronal networks of salience and spatial detection in the murine superior colliculus","_id":"266D407A-B435-11E9-9278-68D0E5697425","grant_number":"LT000256"},{"name":"Connecting sensory with motor processing in the superior colliculus","grant_number":"ALTF 1098-2017","_id":"264FEA02-B435-11E9-9278-68D0E5697425"}],"publisher":"eLife Sciences Publications","day":"15","type":"journal_article","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"status":"public","language":[{"iso":"eng"}],"corr_author":"1","department":[{"_id":"MaJö"},{"_id":"PeJo"}],"external_id":{"pmid":["36040301"],"isi":["000892204300001"]},"date_created":"2023-01-16T10:04:15Z","publication_status":"published","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"abstract":[{"lang":"eng","text":"To understand the function of neuronal circuits, it is crucial to disentangle the connectivity patterns within the network. However, most tools currently used to explore connectivity have low throughput, low selectivity, or limited accessibility. Here, we report the development of an improved packaging system for the production of the highly neurotropic RVdGenvA-CVS-N2c rabies viral vectors, yielding titers orders of magnitude higher with no background contamination, at a fraction of the production time, while preserving the efficiency of transsynaptic labeling. Along with the production pipeline, we developed suites of ‘starter’ AAV and bicistronic RVdG-CVS-N2c vectors, enabling retrograde labeling from a wide range of neuronal populations, tailored for diverse experimental requirements. We demonstrate the power and flexibility of the new system by uncovering hidden local and distal inhibitory connections in the mouse hippocampal formation and by imaging the functional properties of a cortical microcircuit across weeks. Our novel production pipeline provides a convenient approach to generate new rabies vectors, while our toolkit flexibly and efficiently expands the current capacity to label, manipulate and image the neuronal activity of interconnected neuronal circuits in vitro and in vivo."}],"article_number":"79848","quality_controlled":"1","volume":11,"ec_funded":1,"intvolume":"        11","isi":1,"author":[{"orcid":"0000-0002-4792-1881","full_name":"Sumser, Anton L","last_name":"Sumser","id":"3320A096-F248-11E8-B48F-1D18A9856A87","first_name":"Anton L"},{"orcid":"0000-0002-3937-1330","full_name":"Jösch, Maximilian A","last_name":"Jösch","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","first_name":"Maximilian A"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","full_name":"Jonas, Peter M","last_name":"Jonas","orcid":"0000-0001-5001-4804"},{"last_name":"Ben Simon","full_name":"Ben Simon, Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","first_name":"Yoav"}],"scopus_import":"1","publication":"eLife","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"file_date_updated":"2023-01-30T11:50:53Z","publication_identifier":{"eissn":["2050-084X"]},"oa":1,"acknowledgement":"We thank F Marr for technical assistance, A Murray for RVdG-CVS-N2c viruses and Neuro2A packaging cell-lines and J Watson for reading the manuscript. This research was supported by the Scientific Service Units (SSU) of IST-Austria through resources provided by the Imaging and Optics Facility (IOF) and the Preclinical Facility (PCF). This project was funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC advanced grant No 692692, PJ, ERC starting grant No 756502, MJ), the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award, PJ), the Human Frontier Science Program (LT000256/2018-L, AS) and EMBO (ALTF 1098-2017, AS).","file":[{"file_id":"12463","date_created":"2023-01-30T11:50:53Z","creator":"dernst","file_name":"2022_eLife_Sumser.pdf","file_size":8506811,"checksum":"5a2a65e3e7225090c3d8199f3bbd7b7b","content_type":"application/pdf","date_updated":"2023-01-30T11:50:53Z","success":1,"relation":"main_file","access_level":"open_access"}],"pmid":1},{"issue":"1","day":"01","publisher":"Wiley","type":"journal_article","tmp":{"short":"CC BY-NC (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","image":"/images/cc_by_nc.png"},"status":"public","page":"173-195","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","date_updated":"2024-10-09T21:04:02Z","oa_version":"Published Version","year":"2022","date_published":"2022-01-01T00:00:00Z","has_accepted_license":"1","citation":{"short":"B. Basilico, L. Ferrucci, P. Ratano, M.T. Golia, A. Grimaldi, M. Rosito, V. Ferretti, I. Reverte, C. Sanchini, M.C. Marrone, M. Giubettini, V. De Turris, D. Salerno, S. Garofalo, M. St‐Pierre, M. Carrier, M. Renzi, F. Pagani, B. Modi, M. Raspa, F. Scavizzi, C.T. Gross, S. Marinelli, M. Tremblay, D. Caprioli, L. Maggi, C. Limatola, S. Di Angelantonio, D. Ragozzino, Glia 70 (2022) 173–195.","mla":"Basilico, Bernadette, et al. “Microglia Control Glutamatergic Synapses in the Adult Mouse Hippocampus.” <i>Glia</i>, vol. 70, no. 1, Wiley, 2022, pp. 173–95, doi:<a href=\"https://doi.org/10.1002/glia.24101\">10.1002/glia.24101</a>.","ieee":"B. Basilico <i>et al.</i>, “Microglia control glutamatergic synapses in the adult mouse hippocampus,” <i>Glia</i>, vol. 70, no. 1. Wiley, pp. 173–195, 2022.","ama":"Basilico B, Ferrucci L, Ratano P, et al. Microglia control glutamatergic synapses in the adult mouse hippocampus. <i>Glia</i>. 2022;70(1):173-195. doi:<a href=\"https://doi.org/10.1002/glia.24101\">10.1002/glia.24101</a>","apa":"Basilico, B., Ferrucci, L., Ratano, P., Golia, M. T., Grimaldi, A., Rosito, M., … Ragozzino, D. (2022). Microglia control glutamatergic synapses in the adult mouse hippocampus. <i>Glia</i>. Wiley. <a href=\"https://doi.org/10.1002/glia.24101\">https://doi.org/10.1002/glia.24101</a>","chicago":"Basilico, Bernadette, Laura Ferrucci, Patrizia Ratano, Maria T. Golia, Alfonso Grimaldi, Maria Rosito, Valentina Ferretti, et al. “Microglia Control Glutamatergic Synapses in the Adult Mouse Hippocampus.” <i>Glia</i>. Wiley, 2022. <a href=\"https://doi.org/10.1002/glia.24101\">https://doi.org/10.1002/glia.24101</a>.","ista":"Basilico B, Ferrucci L, Ratano P, Golia MT, Grimaldi A, Rosito M, Ferretti V, Reverte I, Sanchini C, Marrone MC, Giubettini M, De Turris V, Salerno D, Garofalo S, St‐Pierre M, Carrier M, Renzi M, Pagani F, Modi B, Raspa M, Scavizzi F, Gross CT, Marinelli S, Tremblay M, Caprioli D, Maggi L, Limatola C, Di Angelantonio S, Ragozzino D. 2022. Microglia control glutamatergic synapses in the adult mouse hippocampus. Glia. 70(1), 173–195."},"article_processing_charge":"No","month":"01","title":"Microglia control glutamatergic synapses in the adult mouse hippocampus","_id":"10818","article_type":"original","doi":"10.1002/glia.24101","ddc":["570"],"publication_identifier":{"issn":["0894-1491"],"eissn":["1098-1136"]},"oa":1,"pmid":1,"file":[{"access_level":"open_access","relation":"main_file","success":1,"date_updated":"2022-03-04T08:55:27Z","checksum":"f10a897290e66c0a062e04ba91db6c17","content_type":"application/pdf","file_size":5340294,"creator":"dernst","file_name":"2021_Glia_Basilico.pdf","date_created":"2022-03-04T08:55:27Z","file_id":"10819"}],"acknowledgement":"The work was supported by a grant from MIUR (PRIN 2017HPTFFC_003) to Davide Ragozzino and in part by funds to Silvia Di Angelantonio (CrestOptics-IIT JointLab for Advanced Microscopy) and Daniele Caprioli (Istituto Pasteur-Fondazione Cenci Bolognetti). Bernadette Basilico, and Laura Ferrucci were supported by the PhD program in Clinical-Experimental Neuroscience and Psychiatry, Sapienza University, Rome; Caterina Sanchini was supported by the PhD program in Life Science, Sapienza University, Rome and by the Italian Institute of Technology, Rome. The authors thank Alessandro Felici, Claudia Valeri, Arsenio Armagno, and Senthilkumar Deivasigamani for help with animal husbandry and transgenic colonies management. They also wish to thank Piotr Bregestovski and Michal Schwartz for helpful discussions and criticism. PLX5622 was provided under Materials Transfer Agreement by Plexxikon Inc. (Berkeley, CA). Open Access Funding provided by Universita degli Studi di Roma La Sapienza within the CRUI-CARE Agreement.","intvolume":"        70","isi":1,"scopus_import":"1","publication":"Glia","file_date_updated":"2022-03-04T08:55:27Z","author":[{"last_name":"Basilico","full_name":"Basilico, Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","first_name":"Bernadette","orcid":"0000-0003-1843-3173"},{"last_name":"Ferrucci","full_name":"Ferrucci, Laura","first_name":"Laura"},{"last_name":"Ratano","full_name":"Ratano, Patrizia","first_name":"Patrizia"},{"first_name":"Maria T.","full_name":"Golia, Maria T.","last_name":"Golia"},{"full_name":"Grimaldi, Alfonso","last_name":"Grimaldi","first_name":"Alfonso"},{"first_name":"Maria","full_name":"Rosito, Maria","last_name":"Rosito"},{"first_name":"Valentina","last_name":"Ferretti","full_name":"Ferretti, Valentina"},{"first_name":"Ingrid","last_name":"Reverte","full_name":"Reverte, Ingrid"},{"first_name":"Caterina","full_name":"Sanchini, Caterina","last_name":"Sanchini"},{"first_name":"Maria C.","last_name":"Marrone","full_name":"Marrone, Maria C."},{"first_name":"Maria","last_name":"Giubettini","full_name":"Giubettini, Maria"},{"first_name":"Valeria","last_name":"De Turris","full_name":"De Turris, Valeria"},{"first_name":"Debora","last_name":"Salerno","full_name":"Salerno, Debora"},{"first_name":"Stefano","last_name":"Garofalo","full_name":"Garofalo, Stefano"},{"first_name":"Marie‐Kim","full_name":"St‐Pierre, Marie‐Kim","last_name":"St‐Pierre"},{"first_name":"Micael","last_name":"Carrier","full_name":"Carrier, Micael"},{"full_name":"Renzi, Massimiliano","last_name":"Renzi","first_name":"Massimiliano"},{"last_name":"Pagani","full_name":"Pagani, Francesca","first_name":"Francesca"},{"full_name":"Modi, Brijesh","last_name":"Modi","first_name":"Brijesh"},{"full_name":"Raspa, Marcello","last_name":"Raspa","first_name":"Marcello"},{"first_name":"Ferdinando","last_name":"Scavizzi","full_name":"Scavizzi, Ferdinando"},{"full_name":"Gross, Cornelius T.","last_name":"Gross","first_name":"Cornelius T."},{"first_name":"Silvia","last_name":"Marinelli","full_name":"Marinelli, Silvia"},{"last_name":"Tremblay","full_name":"Tremblay, Marie‐Ève","first_name":"Marie‐Ève"},{"first_name":"Daniele","full_name":"Caprioli, Daniele","last_name":"Caprioli"},{"full_name":"Maggi, Laura","last_name":"Maggi","first_name":"Laura"},{"first_name":"Cristina","last_name":"Limatola","full_name":"Limatola, Cristina"},{"full_name":"Di Angelantonio, Silvia","last_name":"Di Angelantonio","first_name":"Silvia"},{"first_name":"Davide","full_name":"Ragozzino, Davide","last_name":"Ragozzino"}],"keyword":["Cellular and Molecular Neuroscience","Neurology"],"license":"https://creativecommons.org/licenses/by-nc/4.0/","abstract":[{"lang":"eng","text":"Microglia cells are active players in regulating synaptic development and plasticity in the brain. However, how they influence the normal functioning of synapses is largely unknown. In this study, we characterized the effects of pharmacological microglia depletion, achieved by administration of PLX5622, on hippocampal CA3-CA1 synapses of adult wild type mice. Following microglial depletion, we observed a reduction of spontaneous and evoked glutamatergic activity associated with a decrease of dendritic spine density. We also observed the appearance of immature synaptic features and higher levels of plasticity. Microglia depleted mice showed a deficit in the acquisition of the Novel Object Recognition task. These events were accompanied by hippocampal astrogliosis, although in the absence ofneuroinflammatory condition. PLX-induced synaptic changes were absent in Cx3cr1−/− mice, highlighting the role of CX3CL1/CX3CR1 axis in microglia control of synaptic functioning. Remarkably, microglia repopulation after PLX5622 withdrawal was associated with the recovery of hippocampal synapses and learning functions. Altogether, these data demonstrate that microglia contribute to normal synaptic functioning in the adult brain and that their removal induces reversible changes in organization and activity of glutamatergic synapses."}],"quality_controlled":"1","volume":70,"corr_author":"1","language":[{"iso":"eng"}],"date_created":"2022-03-04T08:53:37Z","external_id":{"isi":["000708025800001"],"pmid":["34661306"]},"department":[{"_id":"GaNo"}],"publication_status":"published"},{"ddc":["570"],"doi":"10.7554/elife.75842","article_type":"original","title":"Heterogeneity of the GFP fitness landscape and data-driven protein design","month":"05","_id":"11448","citation":{"ieee":"L. Gonzalez Somermeyer <i>et al.</i>, “Heterogeneity of the GFP fitness landscape and data-driven protein design,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","short":"L. Gonzalez Somermeyer, A. Fleiss, A.S. Mishin, N.G. Bozhanova, A.A. Igolkina, J. Meiler, M.-E. Alaball Pujol, E.V. Putintseva, K.S. Sarkisyan, F. Kondrashov, ELife 11 (2022).","mla":"Gonzalez Somermeyer, Louisa, et al. “Heterogeneity of the GFP Fitness Landscape and Data-Driven Protein Design.” <i>ELife</i>, vol. 11, 75842, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/elife.75842\">10.7554/elife.75842</a>.","chicago":"Gonzalez Somermeyer, Louisa, Aubin Fleiss, Alexander S Mishin, Nina G Bozhanova, Anna A Igolkina, Jens Meiler, Maria-Elisenda Alaball Pujol, Ekaterina V Putintseva, Karen S Sarkisyan, and Fyodor Kondrashov. “Heterogeneity of the GFP Fitness Landscape and Data-Driven Protein Design.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/elife.75842\">https://doi.org/10.7554/elife.75842</a>.","ista":"Gonzalez Somermeyer L, Fleiss A, Mishin AS, Bozhanova NG, Igolkina AA, Meiler J, Alaball Pujol M-E, Putintseva EV, Sarkisyan KS, Kondrashov F. 2022. Heterogeneity of the GFP fitness landscape and data-driven protein design. eLife. 11, 75842.","ama":"Gonzalez Somermeyer L, Fleiss A, Mishin AS, et al. Heterogeneity of the GFP fitness landscape and data-driven protein design. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/elife.75842\">10.7554/elife.75842</a>","apa":"Gonzalez Somermeyer, L., Fleiss, A., Mishin, A. S., Bozhanova, N. G., Igolkina, A. A., Meiler, J., … Kondrashov, F. (2022). Heterogeneity of the GFP fitness landscape and data-driven protein design. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.75842\">https://doi.org/10.7554/elife.75842</a>"},"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"17850"}],"link":[{"relation":"software","url":"https://github.com/aequorea238/Orthologous_GFP_Fitness_Peaks"}]},"article_processing_charge":"No","year":"2022","oa_version":"Published Version","date_updated":"2026-04-07T13:25:01Z","has_accepted_license":"1","date_published":"2022-05-05T00:00:00Z","project":[{"_id":"26580278-B435-11E9-9278-68D0E5697425","grant_number":"771209","name":"Characterizing the fitness landscape on population and global scales","call_identifier":"H2020"},{"call_identifier":"H2020","name":"International IST Doctoral Program","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"status":"public","day":"05","type":"journal_article","publisher":"eLife Sciences Publications","publication_status":"published","language":[{"iso":"eng"}],"corr_author":"1","external_id":{"isi":["000799197200001"],"pmid":["35510622"]},"department":[{"_id":"GradSch"},{"_id":"FyKo"}],"date_created":"2022-06-18T09:06:59Z","quality_controlled":"1","volume":11,"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"abstract":[{"lang":"eng","text":"Studies of protein fitness landscapes reveal biophysical constraints guiding protein evolution and empower prediction of functional proteins. However, generalisation of these findings is limited due to scarceness of systematic data on fitness landscapes of proteins with a defined evolutionary relationship. We characterized the fitness peaks of four orthologous fluorescent proteins with a broad range of sequence divergence. While two of the four studied fitness peaks were sharp, the other two were considerably flatter, being almost entirely free of epistatic interactions. Mutationally robust proteins, characterized by a flat fitness peak, were not optimal templates for machine-learning-driven protein design – instead, predictions were more accurate for fragile proteins with epistatic landscapes. Our work paves insights for practical application of fitness landscape heterogeneity in protein engineering."}],"article_number":"75842","ec_funded":1,"isi":1,"intvolume":"        11","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"author":[{"first_name":"Louisa","id":"4720D23C-F248-11E8-B48F-1D18A9856A87","last_name":"Gonzalez Somermeyer","full_name":"Gonzalez Somermeyer, Louisa","orcid":"0000-0001-9139-5383"},{"last_name":"Fleiss","full_name":"Fleiss, Aubin","first_name":"Aubin"},{"full_name":"Mishin, Alexander S","last_name":"Mishin","first_name":"Alexander S"},{"first_name":"Nina G","last_name":"Bozhanova","full_name":"Bozhanova, Nina G"},{"last_name":"Igolkina","full_name":"Igolkina, Anna A","first_name":"Anna A"},{"first_name":"Jens","last_name":"Meiler","full_name":"Meiler, Jens"},{"first_name":"Maria-Elisenda","full_name":"Alaball Pujol, Maria-Elisenda","last_name":"Alaball Pujol"},{"last_name":"Putintseva","full_name":"Putintseva, Ekaterina V","first_name":"Ekaterina V"},{"first_name":"Karen S","last_name":"Sarkisyan","full_name":"Sarkisyan, Karen S"},{"last_name":"Kondrashov","full_name":"Kondrashov, Fyodor","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","first_name":"Fyodor","orcid":"0000-0001-8243-4694"}],"file_date_updated":"2022-06-20T07:44:19Z","scopus_import":"1","publication":"eLife","oa":1,"publication_identifier":{"issn":["2050-084X"]},"file":[{"success":1,"access_level":"open_access","relation":"main_file","file_size":5297213,"file_name":"2022_eLife_Somermeyer.pdf","creator":"dernst","date_created":"2022-06-20T07:44:19Z","file_id":"11454","date_updated":"2022-06-20T07:44:19Z","content_type":"application/pdf","checksum":"7573c28f44028ab0cc81faef30039e44"}],"acknowledgement":"We thank Ondřej Draganov, Rodrigo Redondo, Bor Kavčič, Mia Juračić and Andrea Pauli for discussion and technical advice. We thank Anita Testa Salmazo for advice on resin protein purification, Dmitry Bolotin and the Milaboratory (milaboratory.com) for access to computing and storage infrastructure, and Josef Houser and Eva Fujdiarova for technical assistance and data interpretation. Core facility Biomolecular Interactions and Crystallization of CEITEC Masaryk University is gratefully acknowledged for the obtaining of the scientific data presented in this paper. This research was supported by the Scientific Service Units (SSU) of IST-Austria\r\nthrough resources provided by the Bioimaging Facility (BIF), and the Life Science Facility (LSF). MiSeq and HiSeq NGS sequencing was performed by the Next Generation Sequencing Facility at Vienna BioCenter Core Facilities (VBCF), member of the Vienna BioCenter (VBC), Austria. FACS was performed at the BioOptics Facility of the Institute of Molecular Pathology (IMP), Austria. We also thank the Biomolecular Crystallography Facility in the Vanderbilt University Center for Structural Biology. We are grateful to Joel M Harp for help with X-ray data collection. This work was supported by the ERC Consolidator grant to FAK (771209—CharFL). KSS acknowledges support by President’s Grant МК–5405.2021.1.4, the Imperial College Research Fellowship and the MRC London Institute of Medical Sciences (UKRI MC-A658-5QEA0).\r\nAF is supported by the Marie Skłodowska-Curie Fellowship (H2020-MSCA-IF-2019, Grant Agreement No. 898203, Project acronym \"FLINDIP\"). Experiments were partially carried out using equipment provided by the Institute of Bioorganic Chemistry of the Russian Academy of Sciences Сore Facility (CKP IBCH). This work was supported by a Russian Science Foundation grant 19-74-10102.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 665,385.","pmid":1},{"volume":84,"quality_controlled":"1","article_number":"74","abstract":[{"text":"Empirical essays of fitness landscapes suggest that they may be rugged, that is having multiple fitness peaks. Such fitness landscapes, those that have multiple peaks, necessarily have special local structures, called reciprocal sign epistasis (Poelwijk et al. in J Theor Biol 272:141–144, 2011). Here, we investigate the quantitative relationship between the number of fitness peaks and the number of reciprocal sign epistatic interactions. Previously, it has been shown (Poelwijk et al. in J Theor Biol 272:141–144, 2011) that pairwise reciprocal sign epistasis is a necessary but not sufficient condition for the existence of multiple peaks. Applying discrete Morse theory, which to our knowledge has never been used in this context, we extend this result by giving the minimal number of reciprocal sign epistatic interactions required to create a given number of peaks.","lang":"eng"}],"publication_status":"published","date_created":"2022-06-17T16:16:15Z","department":[{"_id":"GradSch"},{"_id":"NiBa"},{"_id":"JaMa"}],"external_id":{"pmid":["35713756"],"isi":["000812509800001"]},"corr_author":"1","language":[{"iso":"eng"}],"pmid":1,"file":[{"success":1,"access_level":"open_access","relation":"main_file","file_name":"2022_BulletinMathBiology_Saona.pdf","creator":"dernst","file_id":"11455","date_created":"2022-06-20T07:51:32Z","file_size":463025,"content_type":"application/pdf","checksum":"05a1fe7d10914a00c2bca9b447993a65","date_updated":"2022-06-20T07:51:32Z"}],"acknowledgement":"We are grateful to Herbert Edelsbrunner and Jeferson Zapata for helpful discussions. Open access funding provided by Austrian Science Fund (FWF). Partially supported by the ERC Consolidator (771209–CharFL) and the FWF Austrian Science Fund (I5127-B) grants to FAK.","publication_identifier":{"issn":["0092-8240"],"eissn":["1522-9602"]},"oa":1,"publication":"Bulletin of Mathematical Biology","file_date_updated":"2022-06-20T07:51:32Z","keyword":["Computational Theory and Mathematics","General Agricultural and Biological Sciences","Pharmacology","General Environmental Science","General Biochemistry","Genetics and Molecular Biology","General Mathematics","Immunology","General Neuroscience"],"scopus_import":"1","author":[{"id":"BD1DF4C4-D767-11E9-B658-BC13E6697425","first_name":"Raimundo J","full_name":"Saona Urmeneta, Raimundo J","last_name":"Saona Urmeneta","orcid":"0000-0001-5103-038X"},{"full_name":"Kondrashov, Fyodor","last_name":"Kondrashov","first_name":"Fyodor","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8243-4694"},{"orcid":"0000-0002-6246-1465","id":"4E6DC800-AE37-11E9-AC72-31CAE5697425","first_name":"Kseniia","full_name":"Khudiakova, Kseniia","last_name":"Khudiakova"}],"isi":1,"intvolume":"        84","ec_funded":1,"_id":"11447","month":"06","title":"Relation between the number of peaks and the number of reciprocal sign epistatic interactions","article_processing_charge":"Yes (via OA deal)","related_material":{"link":[{"url":"https://doi.org/10.1007/s11538-022-01118-z","relation":"erratum"}]},"citation":{"ista":"Saona Urmeneta RJ, Kondrashov F, Khudiakova K. 2022. Relation between the number of peaks and the number of reciprocal sign epistatic interactions. Bulletin of Mathematical Biology. 84(8), 74.","chicago":"Saona Urmeneta, Raimundo J, Fyodor Kondrashov, and Kseniia Khudiakova. “Relation between the Number of Peaks and the Number of Reciprocal Sign Epistatic Interactions.” <i>Bulletin of Mathematical Biology</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1007/s11538-022-01029-z\">https://doi.org/10.1007/s11538-022-01029-z</a>.","apa":"Saona Urmeneta, R. J., Kondrashov, F., &#38; Khudiakova, K. (2022). Relation between the number of peaks and the number of reciprocal sign epistatic interactions. <i>Bulletin of Mathematical Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1007/s11538-022-01029-z\">https://doi.org/10.1007/s11538-022-01029-z</a>","ama":"Saona Urmeneta RJ, Kondrashov F, Khudiakova K. Relation between the number of peaks and the number of reciprocal sign epistatic interactions. <i>Bulletin of Mathematical Biology</i>. 2022;84(8). doi:<a href=\"https://doi.org/10.1007/s11538-022-01029-z\">10.1007/s11538-022-01029-z</a>","ieee":"R. J. Saona Urmeneta, F. Kondrashov, and K. Khudiakova, “Relation between the number of peaks and the number of reciprocal sign epistatic interactions,” <i>Bulletin of Mathematical Biology</i>, vol. 84, no. 8. Springer Nature, 2022.","mla":"Saona Urmeneta, Raimundo J., et al. “Relation between the Number of Peaks and the Number of Reciprocal Sign Epistatic Interactions.” <i>Bulletin of Mathematical Biology</i>, vol. 84, no. 8, 74, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1007/s11538-022-01029-z\">10.1007/s11538-022-01029-z</a>.","short":"R.J. Saona Urmeneta, F. Kondrashov, K. Khudiakova, Bulletin of Mathematical Biology 84 (2022)."},"ddc":["510","570"],"article_type":"original","doi":"10.1007/s11538-022-01029-z","status":"public","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"issue":"8","type":"journal_article","day":"17","publisher":"Springer Nature","date_published":"2022-06-17T00:00:00Z","has_accepted_license":"1","project":[{"_id":"26580278-B435-11E9-9278-68D0E5697425","grant_number":"771209","name":"Characterizing the fitness landscape on population and global scales","call_identifier":"H2020"},{"name":"Evolutionary analysis of gene regulation","grant_number":"I05127","_id":"34e076d6-11ca-11ed-8bc3-aec76c41a181"}],"date_updated":"2026-04-15T08:51:10Z","oa_version":"Published Version","year":"2022","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"doi":"10.1038/s41593-022-01167-6","article_type":"original","ddc":["570"],"article_processing_charge":"No","citation":{"mla":"Colombo, Gloria, et al. “A Tool for Mapping Microglial Morphology, MorphOMICs, Reveals Brain-Region and Sex-Dependent Phenotypes.” <i>Nature Neuroscience</i>, vol. 25, no. 10, Springer Nature, 2022, pp. 1379–93, doi:<a href=\"https://doi.org/10.1038/s41593-022-01167-6\">10.1038/s41593-022-01167-6</a>.","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.","ieee":"G. Colombo <i>et al.</i>, “A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes,” <i>Nature Neuroscience</i>, vol. 25, no. 10. Springer Nature, pp. 1379–1393, 2022.","ama":"Colombo G, Cubero RJ, Kanari L, et al. A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes. <i>Nature Neuroscience</i>. 2022;25(10):1379-1393. doi:<a href=\"https://doi.org/10.1038/s41593-022-01167-6\">10.1038/s41593-022-01167-6</a>","apa":"Colombo, G., Cubero, R. J., Kanari, L., Venturino, A., Schulz, R., Scolamiero, M., … Siegert, S. (2022). A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes. <i>Nature Neuroscience</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41593-022-01167-6\">https://doi.org/10.1038/s41593-022-01167-6</a>","chicago":"Colombo, Gloria, Ryan J Cubero, Lida Kanari, Alessandro Venturino, Rouven Schulz, Martina Scolamiero, Jens Agerberg, et al. “A Tool for Mapping Microglial Morphology, MorphOMICs, Reveals Brain-Region and Sex-Dependent Phenotypes.” <i>Nature Neuroscience</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41593-022-01167-6\">https://doi.org/10.1038/s41593-022-01167-6</a>.","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."},"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","status":"public","relation":"dissertation_contains"}]},"_id":"12244","title":"A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes","month":"10","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","page":"1379-1393","project":[{"grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships"},{"_id":"25D4A630-B435-11E9-9278-68D0E5697425","grant_number":"715571","name":"Microglia action towards neuronal circuit formation and function in health and disease","call_identifier":"H2020"}],"date_published":"2022-10-01T00:00:00Z","has_accepted_license":"1","oa_version":"Published Version","year":"2022","date_updated":"2026-04-28T22:30:35Z","day":"01","type":"journal_article","publisher":"Springer Nature","issue":"10","status":"public","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"department":[{"_id":"SaSi"}],"external_id":{"isi":["000862214700001"],"pmid":["36180790"]},"date_created":"2023-01-16T09:53:07Z","language":[{"iso":"eng"}],"corr_author":"1","publication_status":"published","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"}],"volume":25,"quality_controlled":"1","file_date_updated":"2023-01-30T08:06:56Z","author":[{"last_name":"Colombo","full_name":"Colombo, Gloria","first_name":"Gloria","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9434-8902"},{"full_name":"Cubero, Ryan J","last_name":"Cubero","first_name":"Ryan J","id":"850B2E12-9CD4-11E9-837F-E719E6697425","orcid":"0000-0003-0002-1867"},{"last_name":"Kanari","full_name":"Kanari, Lida","first_name":"Lida"},{"orcid":"0000-0003-2356-9403","last_name":"Venturino","full_name":"Venturino, Alessandro","first_name":"Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Schulz","full_name":"Schulz, Rouven","first_name":"Rouven","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5297-733X"},{"last_name":"Scolamiero","full_name":"Scolamiero, Martina","first_name":"Martina"},{"first_name":"Jens","last_name":"Agerberg","full_name":"Agerberg, Jens"},{"last_name":"Mathys","full_name":"Mathys, Hansruedi","first_name":"Hansruedi"},{"full_name":"Tsai, Li-Huei","last_name":"Tsai","first_name":"Li-Huei"},{"first_name":"Wojciech","full_name":"Chachólski, Wojciech","last_name":"Chachólski"},{"full_name":"Hess, Kathryn","last_name":"Hess","first_name":"Kathryn"},{"first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","last_name":"Siegert","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877"}],"keyword":["General Neuroscience"],"publication":"Nature Neuroscience","scopus_import":"1","ec_funded":1,"isi":1,"intvolume":"        25","file":[{"checksum":"28431146873096f52e0107b534f178c9","content_type":"application/pdf","date_updated":"2023-01-30T08:06:56Z","file_name":"2022_NatureNeuroscience_Colombo.pdf","creator":"dernst","file_id":"12437","date_created":"2023-01-30T08:06:56Z","file_size":23789835,"access_level":"open_access","relation":"main_file","success":1}],"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.","pmid":1,"publication_identifier":{"issn":["1097-6256"],"eissn":["1546-1726"]},"oa":1}]