[{"article_number":"e2301449121","project":[{"_id":"25CA28EA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","grant_number":"694539"},{"call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program","grant_number":"665385"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"mla":"Koppensteiner, Peter, et al. “GABAB Receptors Induce Phasic Release from Medial Habenula Terminals through Activity-Dependent Recruitment of Release-Ready Vesicles.” Proceedings of the National Academy of Sciences, vol. 121, no. 8, e2301449121, Proceedings of the National Academy of Sciences, 2024, doi:10.1073/pnas.2301449121.","apa":"Koppensteiner, P., Bhandari, P., Önal, C., Borges Merjane, C., Le Monnier, E., Roy, U., … Shigemoto, R. (2024). GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. Proceedings of the National Academy of Sciences. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2301449121","ama":"Koppensteiner P, Bhandari P, Önal C, et al. GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. Proceedings of the National Academy of Sciences. 2024;121(8). doi:10.1073/pnas.2301449121","short":"P. Koppensteiner, P. Bhandari, C. Önal, C. Borges Merjane, E. Le Monnier, U. Roy, Y. Nakamura, T. Sadakata, M. Sanbo, M. Hirabayashi, J. Rhee, N. Brose, P.M. Jonas, R. Shigemoto, Proceedings of the National Academy of Sciences 121 (2024).","ieee":"P. Koppensteiner et al., “GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles,” Proceedings of the National Academy of Sciences, vol. 121, no. 8. Proceedings of the National Academy of Sciences, 2024.","chicago":"Koppensteiner, Peter, Pradeep Bhandari, Cihan Önal, Carolina Borges Merjane, Elodie Le Monnier, Utsa Roy, Yukihiro Nakamura, et al. “GABAB Receptors Induce Phasic Release from Medial Habenula Terminals through Activity-Dependent Recruitment of Release-Ready Vesicles.” Proceedings of the National Academy of Sciences. Proceedings of the National Academy of Sciences, 2024. https://doi.org/10.1073/pnas.2301449121.","ista":"Koppensteiner P, Bhandari P, Önal C, Borges Merjane C, Le Monnier E, Roy U, Nakamura Y, Sadakata T, Sanbo M, Hirabayashi M, Rhee J, Brose N, Jonas PM, Shigemoto R. 2024. GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. Proceedings of the National Academy of Sciences. 121(8), e2301449121."},"title":"GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles","author":[{"orcid":"0000-0002-3509-1948","full_name":"Koppensteiner, Peter","last_name":"Koppensteiner","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","first_name":"Peter"},{"id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","first_name":"Pradeep","last_name":"Bhandari","full_name":"Bhandari, Pradeep","orcid":"0000-0003-0863-4481"},{"orcid":"0000-0002-2771-2011","full_name":"Önal, Hüseyin C","last_name":"Önal","id":"4659D740-F248-11E8-B48F-1D18A9856A87","first_name":"Hüseyin C"},{"id":"4305C450-F248-11E8-B48F-1D18A9856A87","first_name":"Carolina","last_name":"Borges Merjane","orcid":"0000-0003-0005-401X","full_name":"Borges Merjane, Carolina"},{"last_name":"Le Monnier","full_name":"Le Monnier, Elodie","id":"3B59276A-F248-11E8-B48F-1D18A9856A87","first_name":"Elodie"},{"first_name":"Utsa","id":"4d26cf11-5355-11ee-ae5a-eb05e255b9b2","last_name":"Roy","full_name":"Roy, Utsa"},{"last_name":"Nakamura","full_name":"Nakamura, Yukihiro","first_name":"Yukihiro"},{"last_name":"Sadakata","full_name":"Sadakata, Tetsushi","first_name":"Tetsushi"},{"first_name":"Makoto","last_name":"Sanbo","full_name":"Sanbo, Makoto"},{"first_name":"Masumi","full_name":"Hirabayashi, Masumi","last_name":"Hirabayashi"},{"last_name":"Rhee","full_name":"Rhee, JeongSeop","first_name":"JeongSeop"},{"last_name":"Brose","full_name":"Brose, Nils","first_name":"Nils"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","last_name":"Jonas","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi","full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","last_name":"Shigemoto"}],"external_id":{"pmid":["38346189"]},"article_processing_charge":"Yes (in subscription journal)","acknowledgement":"We thank Erwin Neher and Ipe Ninan for critical comments on the manuscript. This project has received funding from the European Research Council (ERC) and European Commission, under the European Union’s Horizon 2020 research and innovation program (ERC grant agreement no. 694539 to R.S. and the Marie Skłodowska-Curie grant agreement no. 665385 to C.Ö.). This study was supported by the Cooperative Study Program of Center for Animal Resources and Collaborative Study of NINS. We thank Kohgaku Eguchi for statistical analysis, Yu Kasugai for additional EM imaging, Robert Beattie for the design of the slice recovery chamber for Flash and Freeze experiments, Todor Asenov from the ISTA machine shop for custom part preparations for high-pressure freezing, the ISTA preclinical facility for animal caretaking, and the ISTA EM facilities for technical support.","quality_controlled":"1","publisher":"Proceedings of the National Academy of Sciences","oa":1,"day":"20","publication":"Proceedings of the National Academy of Sciences","has_accepted_license":"1","year":"2024","date_published":"2024-02-20T00:00:00Z","doi":"10.1073/pnas.2301449121","date_created":"2024-03-05T09:23:55Z","_id":"15084","status":"public","type":"journal_article","article_type":"original","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"ddc":["570"],"date_updated":"2024-03-12T13:44:18Z","department":[{"_id":"RySh"},{"_id":"PeJo"}],"file_date_updated":"2024-03-12T13:42:42Z","pmid":1,"oa_version":"Published Version","abstract":[{"lang":"eng","text":"GABAB receptor (GBR) activation inhibits neurotransmitter release in axon terminals in the brain, except in medial habenula (MHb) terminals, which show robust potentiation. However, mechanisms underlying this enigmatic potentiation remain elusive. Here, we report that GBR activation on MHb terminals induces an activity-dependent transition from a facilitating, tonic to a depressing, phasic neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked synaptic vesicles (SVs) at the presynaptic active zone (AZ). Strikingly, the depressing phasic release exhibits looser coupling distance than the tonic release. Furthermore, the tonic and phasic release are selectively affected by deletion of synaptoporin (SPO) and Ca\r\n 2+\r\n -dependent activator protein for secretion 2 (CAPS2), respectively. SPO modulates augmentation, the short-term plasticity associated with tonic release, and CAPS2 retains the increased RRP for initial responses in phasic response trains. The cytosolic protein CAPS2 showed a SV-associated distribution similar to the vesicular transmembrane protein SPO, and they were colocalized in the same terminals. We developed the “Flash and Freeze-fracture” method, and revealed the release of SPO-associated vesicles in both tonic and phasic modes and activity-dependent recruitment of CAPS2 to the AZ during phasic release, which lasted several minutes. Overall, these results indicate that GBR activation translocates CAPS2 to the AZ along with the fusion of CAPS2-associated SVs, contributing to persistency of the RRP increase. Thus, we identified structural and molecular mechanisms underlying tonic and phasic neurotransmitter release and their transition by GBR activation in MHb terminals."}],"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"month":"02","intvolume":" 121","file":[{"date_updated":"2024-03-12T13:42:42Z","file_size":13648221,"creator":"dernst","date_created":"2024-03-12T13:42:42Z","file_name":"2024_PNAS_Koppensteiner.pdf","content_type":"application/pdf","access_level":"open_access","relation":"main_file","file_id":"15110","checksum":"b25b2a057c266ff317a48b0d54d6fc8a","success":1}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"publication_status":"published","issue":"8","volume":121,"related_material":{"record":[{"relation":"research_data","status":"public","id":"13173"}],"link":[{"url":"https://ista.ac.at/en/news/neuronal-insights-flash-and-freeze-fracture/","relation":"press_release","description":"News on ISTA Website"}]},"ec_funded":1},{"quality_controlled":"1","publisher":"Elsevier","acknowledgement":"We thank Drs. David DiGregorio and Erwin Neher for critically reading an earlier version of the manuscript, Ralf Schneggenburger for helpful discussions, Benjamin Suter and Katharina Lichter for support with image analysis, Chris Wojtan for advice on numerical solution of partial differential equations, Maria Reva for help with Ripley analysis, Alois Schlögl for programming, and Akari Hagiwara and Toshihisa Ohtsuka for anti-ELKS antibody. We are grateful to Florian Marr, Christina Altmutter, and Vanessa Zheden for excellent technical assistance and to Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA (Electron Microscopy Facility, Preclinical Facility, and Machine Shop). The project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 692692), the Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award; P 36232-B), all to P.J., and a DOC fellowship of the Austrian Academy of Sciences to J.-J.C.","doi":"10.1016/j.neuron.2023.12.002","date_published":"2024-01-11T00:00:00Z","date_created":"2024-01-21T23:00:56Z","day":"11","publication":"Neuron","year":"2024","project":[{"name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"grant_number":"Z00312","name":"The Wittgenstein Prize","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"grant_number":"P36232","name":"Mechanisms of GABA release in hippocampal circuits","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5"},{"_id":"26B66A3E-B435-11E9-9278-68D0E5697425","grant_number":"25383","name":"Development of nanodomain coupling between Ca2+ channels and release sensors at a central inhibitory synapse"}],"title":"Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse","author":[{"full_name":"Chen, JingJing","last_name":"Chen","id":"2C4E65C8-F248-11E8-B48F-1D18A9856A87","first_name":"JingJing"},{"id":"3F99E422-F248-11E8-B48F-1D18A9856A87","first_name":"Walter","full_name":"Kaufmann, Walter","orcid":"0000-0001-9735-5315","last_name":"Kaufmann"},{"first_name":"Chong","id":"3DFD581A-F248-11E8-B48F-1D18A9856A87","last_name":"Chen","full_name":"Chen, Chong"},{"id":"32A73F6C-F248-11E8-B48F-1D18A9856A87","first_name":"Itaru","last_name":"Arai","full_name":"Arai, Itaru"},{"first_name":"Olena","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","last_name":"Kim","full_name":"Kim, Olena"},{"orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi"},{"orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","external_id":{"pmid":["38215739"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"mla":"Chen, JingJing, et al. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” Neuron, Elsevier, doi:10.1016/j.neuron.2023.12.002.","ieee":"J. Chen et al., “Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse,” Neuron. Elsevier.","short":"J. Chen, W. Kaufmann, C. Chen, itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas, Neuron (n.d.).","apa":"Chen, J., Kaufmann, W., Chen, C., Arai, itaru, Kim, O., Shigemoto, R., & Jonas, P. M. (n.d.). Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2023.12.002","ama":"Chen J, Kaufmann W, Chen C, et al. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron. doi:10.1016/j.neuron.2023.12.002","chicago":"Chen, JingJing, Walter Kaufmann, Chong Chen, itaru Arai, Olena Kim, Ryuichi Shigemoto, and Peter M Jonas. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” Neuron. Elsevier, n.d. https://doi.org/10.1016/j.neuron.2023.12.002.","ista":"Chen J, Kaufmann W, Chen C, Arai itaru, Kim O, Shigemoto R, Jonas PM. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron."},"month":"01","scopus_import":"1","oa_version":"None","pmid":1,"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"PreCl"},{"_id":"M-Shop"}],"abstract":[{"text":"The coupling between Ca2+ channels and release sensors is a key factor defining the signaling properties of a synapse. However, the coupling nanotopography at many synapses remains unknown, and it is unclear how it changes during development. To address these questions, we examined coupling at the cerebellar inhibitory basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission by paired recording and intracellular pipette perfusion revealed that the effects of exogenous Ca2+ chelators decreased during development, despite constant reliance of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked vesicles were only clustered at later developmental stages. Modeling suggested a developmental transformation from a more random to a more clustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission.","lang":"eng"}],"related_material":{"record":[{"status":"public","id":"15101","relation":"dissertation_contains"}],"link":[{"description":"News on ISTA Website","relation":"press_release","url":"https://ista.ac.at/en/news/synapses-brought-to-the-point/"}]},"ec_funded":1,"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1097-4199"],"issn":["0896-6273"]},"publication_status":"inpress","status":"public","article_type":"original","type":"journal_article","_id":"14843","department":[{"_id":"PeJo"},{"_id":"EM-Fac"},{"_id":"RySh"}],"date_updated":"2024-03-14T13:14:18Z"},{"status":"public","type":"dissertation","tmp":{"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)","short":"CC BY (4.0)"},"_id":"15101","department":[{"_id":"GradSch"},{"_id":"PeJo"}],"file_date_updated":"2024-03-12T07:12:17Z","ddc":["570"],"supervisor":[{"orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"date_updated":"2024-03-14T13:14:19Z","month":"03","alternative_title":["ISTA Thesis"],"oa_version":"Published Version","acknowledged_ssus":[{"_id":"EM-Fac"}],"related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"14843"}]},"ec_funded":1,"file":[{"creator":"jchen","date_updated":"2024-03-12T07:12:17Z","file_size":11271363,"date_created":"2024-03-11T14:10:58Z","file_name":"Thesis_Jingjing CHEN.docx","access_level":"closed","relation":"source_file","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_id":"15104","checksum":"db4947474ffa271e66c254b6fe876a55"},{"access_level":"closed","relation":"main_file","content_type":"application/pdf","embargo_to":"open_access","checksum":"a5eeae8b5702cd540f5d03469bc33dde","file_id":"15105","embargo":"2024-04-01","creator":"jchen","date_updated":"2024-03-11T14:11:06Z","file_size":16627311,"date_created":"2024-03-11T14:11:06Z","file_name":"Thesis_Jingjing CHEN_merged.pdf"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2663 - 337X"]},"degree_awarded":"PhD","publication_status":"published","project":[{"grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"name":"The Wittgenstein Prize","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","grant_number":"P36232","name":"Mechanisms of GABA release in hippocampal circuits"},{"grant_number":"25383","name":"Development of nanodomain coupling between Ca2+ channels and release sensors at a central inhibitory synapse","_id":"26B66A3E-B435-11E9-9278-68D0E5697425"}],"title":"Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse","author":[{"id":"2C4E65C8-F248-11E8-B48F-1D18A9856A87","first_name":"JingJing","full_name":"Chen, JingJing","last_name":"Chen"}],"article_processing_charge":"No","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","citation":{"ieee":"J. Chen, “Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse,” Institute of Science and Technology Austria, 2024.","short":"J. Chen, Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse, Institute of Science and Technology Austria, 2024.","apa":"Chen, J. (2024). Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:15101","ama":"Chen J. Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse. 2024. doi:10.15479/at:ista:15101","mla":"Chen, JingJing. Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse. Institute of Science and Technology Austria, 2024, doi:10.15479/at:ista:15101.","ista":"Chen J. 2024. Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse. Institute of Science and Technology Austria.","chicago":"Chen, JingJing. “Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse.” Institute of Science and Technology Austria, 2024. https://doi.org/10.15479/at:ista:15101."},"publisher":"Institute of Science and Technology Austria","date_published":"2024-03-11T00:00:00Z","doi":"10.15479/at:ista:15101","date_created":"2024-03-11T10:09:54Z","page":"84","day":"11","has_accepted_license":"1","year":"2024"},{"acknowledgement":"We thank previous students, postdocs, and collaborators, particularly J. Geiger, and (in alphabetical order) H. Alle, J. Bischofberger, C. Borges-Merjane, D. Engel, M. Frotscher, S. Hallermann, M. Heckmann, S. Jamrichova, O. Kim, L. Li, K. Lichter, P. Lin, J. Lübke, Y. Okamoto, C. Pawlu, C. Schmidt-Hieber, N. Spruston, and N. Vyleta for their outstanding experimental contributions. We also thank P. Castillo, J. Geiger, T. Sakaba, S. Siegert, T. Vogels, and J. Watson for critically reading the manuscript, E. Kralli-Beller for text editing, and J. Malikovic and L. Slomianka for useful discussions. We apologize that, due to space constraints, not all relevant papers could be cited.\r\nThis project was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement 692692, AdG “GIANTSYN”) and the Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein Award; P 36232-B, stand-alone grant), both to P.J.","publisher":"AAAS","quality_controlled":"1","year":"2024","day":"08","publication":"Science","page":"eadg6757","doi":"10.1126/science.adg6757","date_published":"2024-03-08T00:00:00Z","date_created":"2024-03-17T23:00:57Z","project":[{"grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312","name":"The Wittgenstein Prize"},{"_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","grant_number":"P36232","name":"Mechanisms of GABA release in hippocampal circuits"}],"citation":{"mla":"Vandael, David H., and Peter M. Jonas. “Structure, Biophysics, and Circuit Function of a ‘Giant’ Cortical Presynaptic Terminal.” Science, vol. 383, no. 6687, AAAS, 2024, p. eadg6757, doi:10.1126/science.adg6757.","ieee":"D. H. Vandael and P. M. Jonas, “Structure, biophysics, and circuit function of a ‘giant’ cortical presynaptic terminal,” Science, vol. 383, no. 6687. AAAS, p. eadg6757, 2024.","short":"D.H. Vandael, P.M. Jonas, Science 383 (2024) eadg6757.","apa":"Vandael, D. H., & Jonas, P. M. (2024). Structure, biophysics, and circuit function of a “giant” cortical presynaptic terminal. Science. AAAS. https://doi.org/10.1126/science.adg6757","ama":"Vandael DH, Jonas PM. Structure, biophysics, and circuit function of a “giant” cortical presynaptic terminal. Science. 2024;383(6687):eadg6757. doi:10.1126/science.adg6757","chicago":"Vandael, David H, and Peter M Jonas. “Structure, Biophysics, and Circuit Function of a ‘Giant’ Cortical Presynaptic Terminal.” Science. AAAS, 2024. https://doi.org/10.1126/science.adg6757.","ista":"Vandael DH, Jonas PM. 2024. Structure, biophysics, and circuit function of a ‘giant’ cortical presynaptic terminal. Science. 383(6687), eadg6757."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"orcid":"0000-0001-7577-1676","full_name":"Vandael, David H","last_name":"Vandael","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","first_name":"David H"},{"first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas"}],"article_processing_charge":"No","external_id":{"pmid":["38452088"]},"title":"Structure, biophysics, and circuit function of a \"giant\" cortical presynaptic terminal","abstract":[{"text":"The hippocampal mossy fiber synapse, formed between axons of dentate gyrus granule cells and dendrites of CA3 pyramidal neurons, is a key synapse in the trisynaptic circuitry of the hippocampus. Because of its comparatively large size, this synapse is accessible to direct presynaptic recording, allowing a rigorous investigation of the biophysical mechanisms of synaptic transmission and plasticity. Furthermore, because of its placement in the very center of the hippocampal memory circuit, this synapse seems to be critically involved in several higher network functions, such as learning, memory, pattern separation, and pattern completion. Recent work based on new technologies in both nanoanatomy and nanophysiology, including presynaptic patch-clamp recording, paired recording, super-resolution light microscopy, and freeze-fracture and “flash-and-freeze” electron microscopy, has provided new insights into the structure, biophysics, and network function of this intriguing synapse. This brings us one step closer to answering a fundamental question in neuroscience: how basic synaptic properties shape higher network computations.","lang":"eng"}],"pmid":1,"oa_version":"None","scopus_import":"1","month":"03","intvolume":" 383","publication_identifier":{"eissn":["1095-9203"]},"publication_status":"published","language":[{"iso":"eng"}],"issue":"6687","volume":383,"ec_funded":1,"_id":"15117","type":"journal_article","article_type":"review","status":"public","date_updated":"2024-03-20T07:42:52Z","department":[{"_id":"PeJo"}]},{"publication_identifier":{"issn":["1064-3745"],"isbn":["978-1-0716-3003-7"],"eissn":["1940-6029"],"eisbn":["978-1-0716-3004-4"]},"publication_status":"published","language":[{"iso":"eng"}],"volume":2633,"abstract":[{"lang":"eng","text":"Here we describe the in vivo DNA assembly approach, where molecular cloning procedures are performed using an E. coli recA-independent recombination pathway, which assembles linear fragments of DNA with short homologous termini. This pathway is present in all standard laboratory E. coli strains and, by bypassing the need for in vitro DNA assembly, allows simplified molecular cloning to be performed without the plasmid instability issues associated with specialized recombination-cloning bacterial strains. The methodology requires specific primer design and can perform all standard plasmid modifications (insertions, deletions, mutagenesis, and sub-cloning) in a rapid, simple, and cost-efficient manner, as it does not require commercial kits or specialized bacterial strains. Additionally, this approach can be used to perform complex procedures such as multiple modifications to a plasmid, as up to 6 linear fragments can be assembled in vivo by this recombination pathway. Procedures generally require less than 3 h, involving PCR amplification, DpnI digestion of template DNA, and transformation, upon which circular plasmids are assembled. In this chapter we describe the requirements, procedure, and potential pitfalls when using this technique, as well as protocol variations to overcome the most common issues."}],"pmid":1,"oa_version":"None","scopus_import":"1","alternative_title":["Methods in Molecular Biology"],"month":"03","place":"New York, NY, United States","intvolume":" 2633","date_updated":"2023-03-16T08:34:24Z","department":[{"_id":"PeJo"}],"_id":"12720","series_title":"MIMB","type":"book_chapter","status":"public","year":"2023","day":"01","publication":"DNA Manipulation and Analysis","page":"33-44","doi":"10.1007/978-1-0716-3004-4_3","date_published":"2023-03-01T00:00:00Z","date_created":"2023-03-12T23:01:02Z","quality_controlled":"1","publisher":"Springer Nature","citation":{"ista":"Arroyo-Urea S, Watson J, García-Nafría J. 2023.Molecular Cloning Using In Vivo DNA Assembly. In: DNA Manipulation and Analysis. Methods in Molecular Biology, vol. 2633, 33–44.","chicago":"Arroyo-Urea, Sandra, Jake Watson, and Javier García-Nafría. “Molecular Cloning Using In Vivo DNA Assembly.” In DNA Manipulation and Analysis, edited by Garry Scarlett, 2633:33–44. MIMB. New York, NY, United States: Springer Nature, 2023. https://doi.org/10.1007/978-1-0716-3004-4_3.","ieee":"S. Arroyo-Urea, J. Watson, and J. García-Nafría, “Molecular Cloning Using In Vivo DNA Assembly,” in DNA Manipulation and Analysis, vol. 2633, G. Scarlett, Ed. New York, NY, United States: Springer Nature, 2023, pp. 33–44.","short":"S. Arroyo-Urea, J. Watson, J. García-Nafría, in:, G. Scarlett (Ed.), DNA Manipulation and Analysis, Springer Nature, New York, NY, United States, 2023, pp. 33–44.","apa":"Arroyo-Urea, S., Watson, J., & García-Nafría, J. (2023). Molecular Cloning Using In Vivo DNA Assembly. In G. Scarlett (Ed.), DNA Manipulation and Analysis (Vol. 2633, pp. 33–44). New York, NY, United States: Springer Nature. https://doi.org/10.1007/978-1-0716-3004-4_3","ama":"Arroyo-Urea S, Watson J, García-Nafría J. Molecular Cloning Using In Vivo DNA Assembly. In: Scarlett G, ed. DNA Manipulation and Analysis. Vol 2633. MIMB. New York, NY, United States: Springer Nature; 2023:33-44. doi:10.1007/978-1-0716-3004-4_3","mla":"Arroyo-Urea, Sandra, et al. “Molecular Cloning Using In Vivo DNA Assembly.” DNA Manipulation and Analysis, edited by Garry Scarlett, vol. 2633, Springer Nature, 2023, pp. 33–44, doi:10.1007/978-1-0716-3004-4_3."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"last_name":"Arroyo-Urea","full_name":"Arroyo-Urea, Sandra","first_name":"Sandra"},{"last_name":"Watson","orcid":"0000-0002-8698-3823","full_name":"Watson, Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake"},{"last_name":"García-Nafría","full_name":"García-Nafría, Javier","first_name":"Javier"}],"article_processing_charge":"No","external_id":{"pmid":["36853454"]},"title":"Molecular Cloning Using In Vivo DNA Assembly","editor":[{"last_name":"Scarlett","full_name":"Scarlett, Garry","first_name":"Garry"}]},{"volume":24,"issue":"3","publication_status":"published","publication_identifier":{"eissn":["1422-0067"]},"language":[{"iso":"eng"}],"file":[{"checksum":"69a35dcd3e0249f902ab881b06ee2e58","file_id":"12569","success":1,"content_type":"application/pdf","access_level":"open_access","relation":"main_file","date_created":"2023-02-20T07:09:27Z","file_name":"2023_IJMS_Mrestani.pdf","date_updated":"2023-02-20T07:09:27Z","file_size":2823025,"creator":"dernst"}],"scopus_import":"1","intvolume":" 24","month":"01","abstract":[{"lang":"eng","text":"Single-molecule localization microscopy (SMLM) greatly advances structural studies of diverse biological tissues. For example, presynaptic active zone (AZ) nanotopology is resolved in increasing detail. Immunofluorescence imaging of AZ proteins usually relies on epitope preservation using aldehyde-based immunocompetent fixation. Cryofixation techniques, such as high-pressure freezing (HPF) and freeze substitution (FS), are widely used for ultrastructural studies of presynaptic architecture in electron microscopy (EM). HPF/FS demonstrated nearer-to-native preservation of AZ ultrastructure, e.g., by facilitating single filamentous structures. Here, we present a protocol combining the advantages of HPF/FS and direct stochastic optical reconstruction microscopy (dSTORM) to quantify nanotopology of the AZ scaffold protein Bruchpilot (Brp) at neuromuscular junctions (NMJs) of Drosophila melanogaster. Using this standardized model, we tested for preservation of Brp clusters in different FS protocols compared to classical aldehyde fixation. In HPF/FS samples, presynaptic boutons were structurally well preserved with ~22% smaller Brp clusters that allowed quantification of subcluster topology. In summary, we established a standardized near-to-native preparation and immunohistochemistry protocol for SMLM analyses of AZ protein clusters in a defined model synapse. Our protocol could be adapted to study protein arrangements at single-molecule resolution in other intact tissue preparations."}],"oa_version":"Published Version","department":[{"_id":"PeJo"}],"file_date_updated":"2023-02-20T07:09:27Z","date_updated":"2023-08-01T13:16:36Z","ddc":["570"],"tmp":{"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)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original","status":"public","_id":"12567","date_created":"2023-02-19T23:00:56Z","doi":"10.3390/ijms24032128","date_published":"2023-01-21T00:00:00Z","year":"2023","isi":1,"has_accepted_license":"1","publication":"International Journal of Molecular Sciences","day":"21","oa":1,"quality_controlled":"1","publisher":"MDPI","acknowledgement":"This work has been supported by funding of the German Research Foundation (Deutsche Forschungsgemeinschaft [DFG], CRC 166, Project B06 to M.H. and A.-L.S., FOR 3004 SYNABS P1 to M.H.) and by the Interdisciplinary Clinical Research Center (IZKF) Würzburg (Z-3/69 to M.M.P., N-229 to M.H. and A.-L.S.). A.M. is funded by the University of Leipzig Clinician Scientist Program.","external_id":{"isi":["000930324700001"]},"article_processing_charge":"No","author":[{"full_name":"Mrestani, Achmed","last_name":"Mrestani","first_name":"Achmed"},{"id":"39302e62-fcfc-11ec-8196-8b01447dbd3d","first_name":"Katharina","full_name":"Lichter, Katharina","last_name":"Lichter"},{"first_name":"Anna Leena","full_name":"Sirén, Anna Leena","last_name":"Sirén"},{"last_name":"Heckmann","full_name":"Heckmann, Manfred","first_name":"Manfred"},{"first_name":"Mila M.","full_name":"Paul, Mila M.","last_name":"Paul"},{"last_name":"Pauli","full_name":"Pauli, Martin","first_name":"Martin"}],"title":"Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation","citation":{"ieee":"A. Mrestani, K. Lichter, A. L. Sirén, M. Heckmann, M. M. Paul, and M. Pauli, “Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation,” International Journal of Molecular Sciences, vol. 24, no. 3. MDPI, 2023.","short":"A. Mrestani, K. Lichter, A.L. Sirén, M. Heckmann, M.M. Paul, M. Pauli, International Journal of Molecular Sciences 24 (2023).","ama":"Mrestani A, Lichter K, Sirén AL, Heckmann M, Paul MM, Pauli M. Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation. International Journal of Molecular Sciences. 2023;24(3). doi:10.3390/ijms24032128","apa":"Mrestani, A., Lichter, K., Sirén, A. L., Heckmann, M., Paul, M. M., & Pauli, M. (2023). Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation. International Journal of Molecular Sciences. MDPI. https://doi.org/10.3390/ijms24032128","mla":"Mrestani, Achmed, et al. “Single-Molecule Localization Microscopy of Presynaptic Active Zones in Drosophila Melanogaster after Rapid Cryofixation.” International Journal of Molecular Sciences, vol. 24, no. 3, 2128, MDPI, 2023, doi:10.3390/ijms24032128.","ista":"Mrestani A, Lichter K, Sirén AL, Heckmann M, Paul MM, Pauli M. 2023. Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation. International Journal of Molecular Sciences. 24(3), 2128.","chicago":"Mrestani, Achmed, Katharina Lichter, Anna Leena Sirén, Manfred Heckmann, Mila M. Paul, and Martin Pauli. “Single-Molecule Localization Microscopy of Presynaptic Active Zones in Drosophila Melanogaster after Rapid Cryofixation.” International Journal of Molecular Sciences. MDPI, 2023. https://doi.org/10.3390/ijms24032128."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_number":"2128"},{"scopus_import":"1","month":"03","intvolume":" 18","abstract":[{"lang":"eng","text":"Stereological methods for estimating the 3D particle size and density from 2D projections are essential to many research fields. These methods are, however, prone to errors arising from undetected particle profiles due to sectioning and limited resolution, known as ‘lost caps’. A potential solution developed by Keiding, Jensen, and Ranek in 1972, which we refer to as the Keiding model, accounts for lost caps by quantifying the smallest detectable profile in terms of its limiting ‘cap angle’ (ϕ), a size-independent measure of a particle’s distance from the section surface. However, this simple solution has not been widely adopted nor tested. Rather, model-independent design-based stereological methods, which do not explicitly account for lost caps, have come to the fore. Here, we provide the first experimental validation of the Keiding model by comparing the size and density of particles estimated from 2D projections with direct measurement from 3D EM reconstructions of the same tissue. We applied the Keiding model to estimate the size and density of somata, nuclei and vesicles in the cerebellum of mice and rats, where high packing density can be problematic for design-based methods. Our analysis reveals a Gaussian distribution for ϕ rather than a single value. Nevertheless, curve fits of the Keiding model to the 2D diameter distribution accurately estimate the mean ϕ and 3D diameter distribution. While systematic testing using simulations revealed an upper limit to determining ϕ, our analysis shows that estimated ϕ can be used to determine the 3D particle density from the 2D density under a wide range of conditions, and this method is potentially more accurate than minimum-size-based lost-cap corrections and disector methods. Our results show the Keiding model provides an efficient means of accurately estimating the size and density of particles from 2D projections even under conditions of a high density."}],"acknowledged_ssus":[{"_id":"EM-Fac"}],"oa_version":"Published Version","volume":18,"issue":"3 March","ec_funded":1,"publication_identifier":{"eissn":["1932-6203"]},"publication_status":"published","file":[{"creator":"dernst","file_size":7290413,"date_updated":"2023-03-27T06:51:09Z","file_name":"2023_PLoSOne_Rothman.pdf","date_created":"2023-03-27T06:51:09Z","relation":"main_file","access_level":"open_access","content_type":"application/pdf","success":1,"checksum":"2380331ec27cc87808826fc64419ac1c","file_id":"12770"}],"language":[{"iso":"eng"}],"type":"journal_article","article_type":"original","tmp":{"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)","short":"CC BY (4.0)"},"status":"public","_id":"12759","department":[{"_id":"PeJo"}],"file_date_updated":"2023-03-27T06:51:09Z","date_updated":"2023-08-01T13:46:39Z","ddc":["570"],"quality_controlled":"1","publisher":"Public Library of Science","oa":1,"acknowledgement":"We thank the IST Austria Electron Microscopy Facility for technical support, and Diccon Coyle, Andrea Lőrincz and Zoltan Nusser for their helpful comments and discussions.\r\nFunding for JSR and RAS was from the Wellcome Trust (203048; 224499; https://\r\nwellcome.org/). RAS is in receipt of a Wellcome Trust Principal Research Fellowship (224499).\r\nFunding for CBM and PJ was from Fond zur Förderung der Wissenschaftlichen Forschung (V\r\n739-B27 Elise-Richter Programme to CBM, Z 312-B27 Wittgenstein Award to PJ; \r\nhttps://www.fwf.ac.at). PJ received funding from the European Research Council (ERC; https://erc.europa.eu) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 692692). NH was supported by a European\r\nResearch Council Advanced Grant (ERC-AG787157).","doi":"10.1371/journal.pone.0277148","date_published":"2023-03-17T00:00:00Z","date_created":"2023-03-26T22:01:07Z","isi":1,"has_accepted_license":"1","year":"2023","day":"17","publication":"PLoS ONE","project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse"},{"name":"The Wittgenstein Prize","grant_number":"Z00312","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"name":"Structural plasticity at mossy fiber-CA3 synapses","grant_number":"V00739","_id":"2696E7FE-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"article_number":"e0277148","author":[{"first_name":"Jason Seth","full_name":"Rothman, Jason Seth","last_name":"Rothman"},{"first_name":"Carolina","id":"4305C450-F248-11E8-B48F-1D18A9856A87","last_name":"Borges Merjane","orcid":"0000-0003-0005-401X","full_name":"Borges Merjane, Carolina"},{"first_name":"Noemi","full_name":"Holderith, Noemi","last_name":"Holderith"},{"first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M"},{"first_name":"R.","full_name":"Angus Silver, R.","last_name":"Angus Silver"}],"external_id":{"isi":["001024737400001"]},"article_processing_charge":"No","title":"Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy","citation":{"short":"J.S. Rothman, C. Borges Merjane, N. Holderith, P.M. Jonas, R. Angus Silver, PLoS ONE 18 (2023).","ieee":"J. S. Rothman, C. Borges Merjane, N. Holderith, P. M. Jonas, and R. Angus Silver, “Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy,” PLoS ONE, vol. 18, no. 3 March. Public Library of Science, 2023.","ama":"Rothman JS, Borges Merjane C, Holderith N, Jonas PM, Angus Silver R. Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy. PLoS ONE. 2023;18(3 March). doi:10.1371/journal.pone.0277148","apa":"Rothman, J. S., Borges Merjane, C., Holderith, N., Jonas, P. M., & Angus Silver, R. (2023). Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy. PLoS ONE. Public Library of Science. https://doi.org/10.1371/journal.pone.0277148","mla":"Rothman, Jason Seth, et al. “Validation of a Stereological Method for Estimating Particle Size and Density from 2D Projections with High Accuracy.” PLoS ONE, vol. 18, no. 3 March, e0277148, Public Library of Science, 2023, doi:10.1371/journal.pone.0277148.","ista":"Rothman JS, Borges Merjane C, Holderith N, Jonas PM, Angus Silver R. 2023. Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy. PLoS ONE. 18(3 March), e0277148.","chicago":"Rothman, Jason Seth, Carolina Borges Merjane, Noemi Holderith, Peter M Jonas, and R. Angus Silver. “Validation of a Stereological Method for Estimating Particle Size and Density from 2D Projections with High Accuracy.” PLoS ONE. Public Library of Science, 2023. https://doi.org/10.1371/journal.pone.0277148."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8"},{"volume":16,"file":[{"date_created":"2023-02-06T07:56:14Z","file_name":"2022_FrontiersNeuroanatomy_OrtizLeal.pdf","creator":"dernst","date_updated":"2023-02-06T07:56:14Z","file_size":21943473,"checksum":"49cd40f3bda6f267079427042e7d15e3","file_id":"12518","success":1,"access_level":"open_access","relation":"main_file","content_type":"application/pdf"}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1662-5129"]},"publication_status":"published","month":"01","intvolume":" 16","scopus_import":"1","oa_version":"Published Version","pmid":1,"abstract":[{"text":"Introduction: The olfactory system in most mammals is divided into several subsystems based on the anatomical locations of the neuroreceptor cells involved and the receptor families that are expressed. In addition to the main olfactory system and the vomeronasal system, a range of olfactory subsystems converge onto the transition zone located between the main olfactory bulb (MOB) and the accessory olfactory bulb (AOB), which has been termed the olfactory limbus (OL). The OL contains specialized glomeruli that receive noncanonical sensory afferences and which interact with the MOB and AOB. Little is known regarding the olfactory subsystems of mammals other than laboratory rodents.\r\nMethods: We have focused on characterizing the OL in the red fox by performing general and specific histological stainings on serial sections, using both single and double immunohistochemical and lectin-histochemical labeling techniques.\r\nResults: As a result, we have been able to determine that the OL of the red fox (Vulpes vulpes) displays an uncommonly high degree of development and complexity.\r\nDiscussion: This makes this species a novel mammalian model, the study of which could improve our understanding of the noncanonical pathways involved in the processing of chemosensory cues.","lang":"eng"}],"department":[{"_id":"PeJo"}],"file_date_updated":"2023-02-06T07:56:14Z","ddc":["570"],"date_updated":"2023-08-16T11:37:52Z","status":"public","article_type":"original","type":"journal_article","tmp":{"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)","short":"CC BY (4.0)"},"_id":"12515","date_published":"2023-01-10T00:00:00Z","doi":"10.3389/fnana.2022.1097467","date_created":"2023-02-05T23:01:00Z","day":"10","publication":"Frontiers in Neuroanatomy","isi":1,"has_accepted_license":"1","year":"2023","quality_controlled":"1","publisher":"Frontiers","oa":1,"acknowledgement":"This work was partially supported by a grant from “Consello Social Universidade de Santiago de Compostela” 2022-PU004.We would like to show special gratitude to Prof. Ludwig Wagner (Medical University, Vienna) for kindly providing us with the secretagogin antibody. We thank the Wildlife Recovery Centres of Galicia, Dirección Xeral de Patrimonio Natural (Xunta de Galicia, Spain), and Federación Galega de Caza for providing the red foxes used in this study.","title":"The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway","author":[{"first_name":"Irene","last_name":"Ortiz-Leal","full_name":"Ortiz-Leal, Irene"},{"first_name":"Mateo V.","full_name":"Torres, Mateo V.","last_name":"Torres"},{"last_name":"Vargas Barroso","full_name":"Vargas Barroso, Victor M","first_name":"Victor M","id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Fidalgo","full_name":"Fidalgo, Luis Eusebio","first_name":"Luis Eusebio"},{"last_name":"López-Beceiro","full_name":"López-Beceiro, Ana María","first_name":"Ana María"},{"last_name":"Larriva-Sahd","full_name":"Larriva-Sahd, Jorge A.","first_name":"Jorge A."},{"first_name":"Pablo","full_name":"Sánchez-Quinteiro, Pablo","last_name":"Sánchez-Quinteiro"}],"external_id":{"isi":["000919786900001"],"pmid":["36704406"]},"article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"chicago":"Ortiz-Leal, Irene, Mateo V. Torres, Victor M Vargas Barroso, Luis Eusebio Fidalgo, Ana María López-Beceiro, Jorge A. Larriva-Sahd, and Pablo Sánchez-Quinteiro. “The Olfactory Limbus of the Red Fox (Vulpes Vulpes). New Insights Regarding a Noncanonical Olfactory Bulb Pathway.” Frontiers in Neuroanatomy. Frontiers, 2023. https://doi.org/10.3389/fnana.2022.1097467.","ista":"Ortiz-Leal I, Torres MV, Vargas Barroso VM, Fidalgo LE, López-Beceiro AM, Larriva-Sahd JA, Sánchez-Quinteiro P. 2023. The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway. Frontiers in Neuroanatomy. 16, 1097467.","mla":"Ortiz-Leal, Irene, et al. “The Olfactory Limbus of the Red Fox (Vulpes Vulpes). New Insights Regarding a Noncanonical Olfactory Bulb Pathway.” Frontiers in Neuroanatomy, vol. 16, 1097467, Frontiers, 2023, doi:10.3389/fnana.2022.1097467.","short":"I. Ortiz-Leal, M.V. Torres, V.M. Vargas Barroso, L.E. Fidalgo, A.M. López-Beceiro, J.A. Larriva-Sahd, P. Sánchez-Quinteiro, Frontiers in Neuroanatomy 16 (2023).","ieee":"I. Ortiz-Leal et al., “The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway,” Frontiers in Neuroanatomy, vol. 16. Frontiers, 2023.","ama":"Ortiz-Leal I, Torres MV, Vargas Barroso VM, et al. The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway. Frontiers in Neuroanatomy. 2023;16. doi:10.3389/fnana.2022.1097467","apa":"Ortiz-Leal, I., Torres, M. V., Vargas Barroso, V. M., Fidalgo, L. E., López-Beceiro, A. M., Larriva-Sahd, J. A., & Sánchez-Quinteiro, P. (2023). The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway. Frontiers in Neuroanatomy. Frontiers. https://doi.org/10.3389/fnana.2022.1097467"},"article_number":"1097467"},{"oa_version":"Published Version","abstract":[{"lang":"eng","text":"AMPA glutamate receptors (AMPARs) mediate excitatory neurotransmission throughout the brain. Their signalling is uniquely diversified by brain region-specific auxiliary subunits, providing an opportunity for the development of selective therapeutics. AMPARs associated with TARP γ8 are enriched in the hippocampus, and are targets of emerging anti-epileptic drugs. To understand their therapeutic activity, we determined cryo-EM structures of the GluA1/2-γ8 receptor associated with three potent, chemically diverse ligands. We find that despite sharing a lipid-exposed and water-accessible binding pocket, drug action is differentially affected by binding-site mutants. Together with patch-clamp recordings and MD simulations we also demonstrate that ligand-triggered reorganisation of the AMPAR-TARP interface contributes to modulation. Unexpectedly, one ligand (JNJ-61432059) acts bifunctionally, negatively affecting GluA1 but exerting positive modulatory action on GluA2-containing AMPARs, in a TARP stoichiometry-dependent manner. These results further illuminate the action of TARPs, demonstrate the sensitive balance between positive and negative modulatory action, and provide a mechanistic platform for development of both positive and negative selective AMPAR modulators."}],"intvolume":" 14","month":"03","scopus_import":"1","language":[{"iso":"eng"}],"file":[{"date_created":"2023-04-03T06:38:56Z","file_name":"2023_NatureComm_Zhang.pdf","date_updated":"2023-04-03T06:38:56Z","file_size":2613996,"creator":"dernst","checksum":"0a97b31191432dae5853bbb5ccb7698d","file_id":"12797","success":1,"content_type":"application/pdf","access_level":"open_access","relation":"main_file"}],"publication_status":"published","publication_identifier":{"eissn":["2041-1723"]},"volume":14,"_id":"12786","status":"public","tmp":{"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)","short":"CC BY (4.0)"},"article_type":"original","type":"journal_article","ddc":["570"],"date_updated":"2023-12-13T11:15:58Z","file_date_updated":"2023-04-03T06:38:56Z","department":[{"_id":"PeJo"}],"acknowledgement":"We thank James Krieger for generating the ‘proDy’ interaction maps in Fig. 5B and S7C, and Jan-Niklas Dohrke for critically reading the manuscript. We thank members of the Greger lab for insightful comments during this study. We acknowledge Trevor Rutherford for confirming ligand integrity by NMR. We are also grateful to LMB scientific computing and the EM facility for their support. This research was funded in part by the Wellcome Trust (223194/Z/21/Z) to I.H.G. For the purpose of Open Access, the MRC Laboratory of Molecular Biology has applied a CC BY public copyright licence to any Author Accepted Manuscript (AAM) version arising from this submission. Further funding came from the Medical Research Council (MRU105174197) to I.H.G, and NIH grant (R56/R01MH123474) to T.N.","oa":1,"publisher":"Springer Nature","quality_controlled":"1","publication":"Nature Communications","day":"25","year":"2023","isi":1,"has_accepted_license":"1","date_created":"2023-04-02T22:01:09Z","date_published":"2023-03-25T00:00:00Z","doi":"10.1038/s41467-023-37259-5","article_number":"1659","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"chicago":"Zhang, Danyang, Remigijus Lape, Saher A. Shaikh, Bianka K. Kohegyi, Jake Watson, Ondrej Cais, Terunaga Nakagawa, and Ingo H. Greger. “Modulatory Mechanisms of TARP Γ8-Selective AMPA Receptor Therapeutics.” Nature Communications. Springer Nature, 2023. https://doi.org/10.1038/s41467-023-37259-5.","ista":"Zhang D, Lape R, Shaikh SA, Kohegyi BK, Watson J, Cais O, Nakagawa T, Greger IH. 2023. Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics. Nature Communications. 14, 1659.","mla":"Zhang, Danyang, et al. “Modulatory Mechanisms of TARP Γ8-Selective AMPA Receptor Therapeutics.” Nature Communications, vol. 14, 1659, Springer Nature, 2023, doi:10.1038/s41467-023-37259-5.","ieee":"D. Zhang et al., “Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics,” Nature Communications, vol. 14. Springer Nature, 2023.","short":"D. Zhang, R. Lape, S.A. Shaikh, B.K. Kohegyi, J. Watson, O. Cais, T. Nakagawa, I.H. Greger, Nature Communications 14 (2023).","apa":"Zhang, D., Lape, R., Shaikh, S. A., Kohegyi, B. K., Watson, J., Cais, O., … Greger, I. H. (2023). Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-023-37259-5","ama":"Zhang D, Lape R, Shaikh SA, et al. Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics. Nature Communications. 2023;14. doi:10.1038/s41467-023-37259-5"},"title":"Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics","article_processing_charge":"No","external_id":{"isi":["001066658700003"]},"author":[{"first_name":"Danyang","full_name":"Zhang, Danyang","last_name":"Zhang"},{"first_name":"Remigijus","full_name":"Lape, Remigijus","last_name":"Lape"},{"first_name":"Saher A.","last_name":"Shaikh","full_name":"Shaikh, Saher A."},{"last_name":"Kohegyi","full_name":"Kohegyi, Bianka K.","first_name":"Bianka K."},{"last_name":"Watson","full_name":"Watson, Jake","orcid":"0000-0002-8698-3823","first_name":"Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"first_name":"Ondrej","last_name":"Cais","full_name":"Cais, Ondrej"},{"first_name":"Terunaga","full_name":"Nakagawa, Terunaga","last_name":"Nakagawa"},{"full_name":"Greger, Ingo H.","last_name":"Greger","first_name":"Ingo H."}]},{"volume":20,"related_material":{"record":[{"relation":"research_data","status":"public","id":"12817"},{"relation":"shorter_version","id":"14770","status":"public"}],"link":[{"relation":"software","url":"https://github.com/danzllab/LIONESS"}]},"ec_funded":1,"publication_identifier":{"eissn":["1548-7105"],"issn":["1548-7091"]},"publication_status":"published","language":[{"iso":"eng"}],"scopus_import":"1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1038/s41592-023-01936-6"}],"month":"08","intvolume":" 20","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"E-Lib"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"abstract":[{"lang":"eng","text":"Three-dimensional (3D) reconstruction of living brain tissue down to an individual synapse level would create opportunities for decoding the dynamics and structure–function relationships of the brain’s complex and dense information processing network; however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise ratio and prohibitive light burden in optical imaging, whereas electron microscopy is inherently static. Here we solved these challenges by developing an integrated optical/machine-learning technology, LIONESS (live information-optimized nanoscopy enabling saturated segmentation). This leverages optical modifications to stimulated emission depletion microscopy in comprehensively, extracellularly labeled tissue and previous information on sample structure via machine learning to simultaneously achieve isotropic super-resolution, high signal-to-noise ratio and compatibility with living tissue. This allows dense deep-learning-based instance segmentation and 3D reconstruction at a synapse level, incorporating molecular, activity and morphodynamic information. LIONESS opens up avenues for studying the dynamic functional (nano-)architecture of living brain tissue."}],"oa_version":"Published Version","pmid":1,"department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"},{"_id":"Bio"}],"date_updated":"2024-01-10T08:37:48Z","type":"journal_article","article_type":"original","status":"public","_id":"13267","page":"1256-1265","doi":"10.1038/s41592-023-01936-6","date_published":"2023-08-01T00:00:00Z","date_created":"2023-07-23T22:01:13Z","isi":1,"year":"2023","day":"01","publication":"Nature Methods","quality_controlled":"1","publisher":"Springer Nature","oa":1,"acknowledgement":"We thank J. Vorlaufer, N. Agudelo and A. Wartak for microscope maintenance and troubleshooting, C. Kreuzinger and A. Freeman for technical assistance, M. Šuplata for hardware control support and M. Cunha dos Santos for initial exploration of software. We\r\nthank P. Henderson for advice on deep-learning training and M. Sixt, S. Boyd and T. Weiss for discussions and critical reading of the manuscript. L. Lavis (Janelia Research Campus) generously provided the JF585-HaloTag ligand. We acknowledge expert support by IST\r\nAustria’s scientific computing, imaging and optics, preclinical, library and laboratory support facilities and by the Miba machine shop. We gratefully acknowledge funding by the following sources: Austrian Science Fund (F.W.F.) grant no. I3600-B27 (J.G.D.), grant no. DK W1232\r\n(J.G.D. and J.M.M.) and grant no. Z 312-B27, Wittgenstein award (P.J.); the Gesellschaft für Forschungsförderung NÖ grant no. LSC18-022 (J.G.D.); an ISTA Interdisciplinary project grant (J.G.D. and B.B.); the European Union’s Horizon 2020 research and innovation programme,\r\nMarie-Skłodowska Curie grant 665385 (J.M.M. and J.L.); the European Union’s Horizon 2020 research and innovation programme, European Research Council grant no. 715767, MATERIALIZABLE (B.B.); grant no. 715508, REVERSEAUTISM (G.N.); grant no. 695568, SYNNOVATE (S.G.N.G.); and grant no. 692692, GIANTSYN (P.J.); the Simons\r\nFoundation Autism Research Initiative grant no. 529085 (S.G.N.G.); the Wellcome Trust Technology Development grant no. 202932 (S.G.N.G.); the Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.);\r\nthe Human Frontier Science Program postdoctoral fellowship LT000557/2018 (W.J.); and the National Science Foundation grant no. IIS-1835231 (H.P.) and NCS-FO-2124179 (H.P.).","author":[{"first_name":"Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","last_name":"Velicky","full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431"},{"last_name":"Miguel Villalba","full_name":"Miguel Villalba, Eder","orcid":"0000-0001-5665-0430","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","first_name":"Eder"},{"full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235","last_name":"Michalska","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","first_name":"Julia M"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","full_name":"Lyudchik, Julia","last_name":"Lyudchik"},{"full_name":"Wei, Donglai","last_name":"Wei","first_name":"Donglai"},{"first_name":"Zudi","last_name":"Lin","full_name":"Lin, Zudi"},{"first_name":"Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","full_name":"Watson, Jake","orcid":"0000-0002-8698-3823","last_name":"Watson"},{"first_name":"Jakob","full_name":"Troidl, Jakob","last_name":"Troidl"},{"first_name":"Johanna","last_name":"Beyer","full_name":"Beyer, Johanna"},{"id":"43DF3136-F248-11E8-B48F-1D18A9856A87","first_name":"Yoav","last_name":"Ben Simon","full_name":"Ben Simon, Yoav"},{"full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M"},{"id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","first_name":"Wiebke","full_name":"Jahr, Wiebke","last_name":"Jahr"},{"last_name":"Cenameri","full_name":"Cenameri, Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban"},{"last_name":"Broichhagen","full_name":"Broichhagen, Johannes","first_name":"Johannes"},{"first_name":"Seth G.N.","full_name":"Grant, Seth G.N.","last_name":"Grant"},{"last_name":"Jonas","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"},{"last_name":"Pfister","full_name":"Pfister, Hanspeter","first_name":"Hanspeter"},{"first_name":"Bernd","id":"49876194-F248-11E8-B48F-1D18A9856A87","last_name":"Bickel","orcid":"0000-0001-6511-9385","full_name":"Bickel, Bernd"},{"full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","last_name":"Danzl","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"Yes","external_id":{"isi":["001025621500001"],"pmid":["37429995"]},"title":"Dense 4D nanoscale reconstruction of living brain tissue","citation":{"ista":"Velicky P, Miguel Villalba E, Michalska JM, Lyudchik J, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. 2023. Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. 20, 1256–1265.","chicago":"Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Julia Lyudchik, Donglai Wei, Zudi Lin, Jake Watson, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” Nature Methods. Springer Nature, 2023. https://doi.org/10.1038/s41592-023-01936-6.","ieee":"P. Velicky et al., “Dense 4D nanoscale reconstruction of living brain tissue,” Nature Methods, vol. 20. Springer Nature, pp. 1256–1265, 2023.","short":"P. Velicky, E. Miguel Villalba, J.M. Michalska, J. Lyudchik, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, Nature Methods 20 (2023) 1256–1265.","apa":"Velicky, P., Miguel Villalba, E., Michalska, J. M., Lyudchik, J., Wei, D., Lin, Z., … Danzl, J. G. (2023). Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. Springer Nature. https://doi.org/10.1038/s41592-023-01936-6","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. 2023;20:1256-1265. doi:10.1038/s41592-023-01936-6","mla":"Velicky, Philipp, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” Nature Methods, vol. 20, Springer Nature, 2023, pp. 1256–65, doi:10.1038/s41592-023-01936-6."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","project":[{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules"},{"call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425","name":"Molecular Drug Targets","grant_number":"W1232-B24"},{"name":"The Wittgenstein Prize","grant_number":"Z00312","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"_id":"23889792-32DE-11EA-91FC-C7463DDC885E","name":"High content imaging to decode human immune cell interactions in health and allergic disease"},{"call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program","grant_number":"665385"},{"grant_number":"715767","name":"MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling","call_identifier":"H2020","_id":"24F9549A-B435-11E9-9278-68D0E5697425"},{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692"},{"_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","call_identifier":"H2020","name":"Synaptic computations of the hippocampal CA3 circuitry","grant_number":"101026635"},{"name":"High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration","grant_number":"LT00057","_id":"2668BFA0-B435-11E9-9278-68D0E5697425"}]},{"related_material":{"link":[{"description":"Original data for Fig. 5d, Fig. 5d (N2V) and Fig. 5f-i, provided via an external link due to the large size (>10GB) of the datasets. 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Research Data for the Publication “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Institute of Science and Technology Austria, 2023, doi:10.15479/AT:ISTA:13126.","short":"J.G. Danzl, (2023).","ieee":"J. G. Danzl, “Research data for the publication ‘Imaging brain tissue architecture across millimeter to nanometer scales.’” Institute of Science and Technology Austria, 2023.","apa":"Danzl, J. G. (2023). Research data for the publication “Imaging brain tissue architecture across millimeter to nanometer scales.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:13126","ama":"Danzl JG. 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We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease."}],"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"oa_version":"Published Version","scopus_import":"1","main_file_link":[{"url":"https://doi.org/10.1038/s41587-023-01911-8","open_access":"1"}],"month":"08","publication_identifier":{"eissn":["1546-1696"],"issn":["1087-0156"]},"publication_status":"epub_ahead","language":[{"iso":"eng"}],"related_material":{"record":[{"id":"13126","status":"public","relation":"research_data"}],"link":[{"relation":"software","url":"https://github.com/danzllab/CATS"}]},"ec_funded":1,"_id":"14257","type":"journal_article","article_type":"original","status":"public","date_updated":"2024-02-21T12:18:18Z","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"},{"_id":"Bio"},{"_id":"RySh"}],"acknowledgement":"We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I. Erber for technical assistance; and M. Tomschik for support with obtaining human samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata for computational support and hardware control. We are grateful to R. Shigemoto and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University) for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly provided by S. Grant (University of Edinburgh). We acknowledge expert support by Institute of Science and Technology Austria’s scientific computing, imaging and optics, preclinical and lab support facilities and by the Miba machine shop and library. We gratefully acknowledge funding by the following sources: Austrian Science Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232 (J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award (P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27 (R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 692692 – GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).","publisher":"Springer Nature","quality_controlled":"1","oa":1,"isi":1,"year":"2023","day":"31","publication":"Nature Biotechnology","date_published":"2023-08-31T00:00:00Z","doi":"10.1038/s41587-023-01911-8","date_created":"2023-09-03T22:01:15Z","project":[{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules"},{"name":"Molecular Drug Targets","grant_number":"W1232-B24","_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312","name":"The Wittgenstein Prize"},{"_id":"23889792-32DE-11EA-91FC-C7463DDC885E","name":"High content imaging to decode human immune cell interactions in health and allergic disease"},{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692"},{"grant_number":"665385","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"name":"Synaptic computations of the hippocampal CA3 circuitry","grant_number":"101026635","call_identifier":"H2020","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9"}],"citation":{"chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Nature Biotechnology. Springer Nature, 2023. https://doi.org/10.1038/s41587-023-01911-8.","ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino G, Jonas PM, Danzl JG. 2023. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology.","mla":"Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Nature Biotechnology, Springer Nature, 2023, doi:10.1038/s41587-023-01911-8.","apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (2023). Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. Springer Nature. https://doi.org/10.1038/s41587-023-01911-8","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. 2023. doi:10.1038/s41587-023-01911-8","ieee":"J. M. Michalska et al., “Imaging brain tissue architecture across millimeter to nanometer scales,” Nature Biotechnology. Springer Nature, 2023.","short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology (2023)."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235","last_name":"Michalska","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","first_name":"Julia M"},{"last_name":"Lyudchik","full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia"},{"last_name":"Velicky","full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431","first_name":"Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87"},{"id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","first_name":"Hana","full_name":"Korinkova, Hana","last_name":"Korinkova"},{"orcid":"0000-0002-8698-3823","full_name":"Watson, Jake","last_name":"Watson","first_name":"Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"last_name":"Cenameri","full_name":"Cenameri, Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban"},{"first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","last_name":"Sommer"},{"first_name":"Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207","full_name":"Amberg, Nicole","last_name":"Amberg"},{"first_name":"Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2356-9403","full_name":"Venturino, Alessandro","last_name":"Venturino"},{"first_name":"Karl","full_name":"Roessler, Karl","last_name":"Roessler"},{"first_name":"Thomas","last_name":"Czech","full_name":"Czech, Thomas"},{"first_name":"Romana","full_name":"Höftberger, Romana","last_name":"Höftberger"},{"first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877","last_name":"Siegert"},{"orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G"}],"external_id":{"isi":["001065254200001"]},"article_processing_charge":"Yes (in subscription journal)","title":"Imaging brain tissue architecture across millimeter to nanometer scales"},{"acknowledgement":"We thank Ondrej Cais for critical reading of the manuscript. We are grateful to LMB\r\nscientific computing and the EM facility for support, Paul Emsley for help with model\r\nbuilding and Takanori Nakane for helpful comments with Relion 3.1. This work was\r\nsupported by grants from the Medical Research Council (MC_U105174197) and BBSRC\r\n(BB/N002113/1) to I.H.G, and grants from the MCIN/AEI/ 10.13039/501100011033 and\r\n“ESF Investing in your future” to B.H (PID2019-106284GA-I00 and RYC2018-025720-I).","oa":1,"quality_controlled":"1","publisher":"Springer Nature","year":"2022","isi":1,"has_accepted_license":"1","publication":"Nature Communications","day":"08","date_created":"2022-02-20T23:01:30Z","doi":"10.1038/s41467-022-28404-7","date_published":"2022-02-08T00:00:00Z","article_number":"734","citation":{"ama":"Herguedas B, Kohegyi BK, Dohrke JN, et al. Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor. Nature Communications. 2022;13. doi:10.1038/s41467-022-28404-7","apa":"Herguedas, B., Kohegyi, B. K., Dohrke, J. N., Watson, J., Zhang, D., Ho, H., … Greger, I. H. (2022). Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-28404-7","short":"B. Herguedas, B.K. Kohegyi, J.N. Dohrke, J. Watson, D. Zhang, H. Ho, S.A. Shaikh, R. Lape, J.M. Krieger, I.H. Greger, Nature Communications 13 (2022).","ieee":"B. Herguedas et al., “Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor,” Nature Communications, vol. 13. Springer Nature, 2022.","mla":"Herguedas, Beatriz, et al. “Mechanisms Underlying TARP Modulation of the GluA1/2-Γ8 AMPA Receptor.” Nature Communications, vol. 13, 734, Springer Nature, 2022, doi:10.1038/s41467-022-28404-7.","ista":"Herguedas B, Kohegyi BK, Dohrke JN, Watson J, Zhang D, Ho H, Shaikh SA, Lape R, Krieger JM, Greger IH. 2022. Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor. Nature Communications. 13, 734.","chicago":"Herguedas, Beatriz, Bianka K. Kohegyi, Jan Niklas Dohrke, Jake Watson, Danyang Zhang, Hinze Ho, Saher A. Shaikh, Remigijus Lape, James M. Krieger, and Ingo H. Greger. “Mechanisms Underlying TARP Modulation of the GluA1/2-Γ8 AMPA Receptor.” Nature Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-28404-7."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","external_id":{"isi":["000757297200008"],"pmid":["35136046"]},"article_processing_charge":"No","author":[{"first_name":"Beatriz","full_name":"Herguedas, Beatriz","last_name":"Herguedas"},{"last_name":"Kohegyi","full_name":"Kohegyi, Bianka K.","first_name":"Bianka K."},{"full_name":"Dohrke, Jan Niklas","last_name":"Dohrke","first_name":"Jan Niklas"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake","full_name":"Watson, Jake","orcid":"0000-0002-8698-3823","last_name":"Watson"},{"first_name":"Danyang","last_name":"Zhang","full_name":"Zhang, Danyang"},{"last_name":"Ho","full_name":"Ho, Hinze","first_name":"Hinze"},{"first_name":"Saher A.","full_name":"Shaikh, Saher A.","last_name":"Shaikh"},{"first_name":"Remigijus","full_name":"Lape, Remigijus","last_name":"Lape"},{"full_name":"Krieger, James M.","last_name":"Krieger","first_name":"James M."},{"last_name":"Greger","full_name":"Greger, Ingo H.","first_name":"Ingo H."}],"title":"Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor","abstract":[{"lang":"eng","text":"AMPA-type glutamate receptors (AMPARs) mediate rapid signal transmission at excitatory\r\nsynapses in the brain. Glutamate binding to the receptor’s ligand-binding domains (LBDs)\r\nleads to ion channel activation and desensitization. Gating kinetics shape synaptic transmission\r\nand are strongly modulated by transmembrane AMPAR regulatory proteins (TARPs)\r\nthrough currently incompletely resolved mechanisms. Here, electron cryo-microscopy\r\nstructures of the GluA1/2 TARP-γ8 complex, in both open and desensitized states\r\n(at 3.5 Å), reveal state-selective engagement of the LBDs by the large TARP-γ8 loop (‘β1’),\r\nelucidating how this TARP stabilizes specific gating states. We further show how TARPs alter\r\nchannel rectification, by interacting with the pore helix of the selectivity filter. Lastly, we\r\nreveal that the Q/R-editing site couples the channel constriction at the filter entrance to the\r\ngate, and forms the major cation binding site in the conduction path. Our results provide a\r\nmechanistic framework of how TARPs modulate AMPAR gating and conductance."}],"oa_version":"Published Version","pmid":1,"scopus_import":"1","intvolume":" 13","month":"02","publication_status":"published","publication_identifier":{"eissn":["20411723"]},"language":[{"iso":"eng"}],"file":[{"success":1,"file_id":"10778","checksum":"d86ee8eabe8b794730729ffbb1a8832e","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_name":"2022_NatureCommunications_Herguedas.pdf","date_created":"2022-02-21T07:59:32Z","file_size":2625540,"date_updated":"2022-02-21T07:59:32Z","creator":"dernst"}],"volume":13,"_id":"10763","tmp":{"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)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original","status":"public","date_updated":"2023-08-02T14:25:33Z","ddc":["570"],"file_date_updated":"2022-02-21T07:59:32Z","department":[{"_id":"PeJo"}]},{"date_updated":"2023-08-03T13:01:19Z","ddc":["570"],"department":[{"_id":"JoCs"},{"_id":"PeJo"},{"_id":"JoDa"}],"file_date_updated":"2022-08-26T11:51:40Z","_id":"11951","type":"journal_article","article_type":"original","tmp":{"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)","short":"CC BY (4.0)"},"status":"public","keyword":["General Physics and Astronomy","General Biochemistry","Genetics and Molecular Biology","General Chemistry","Multidisciplinary"],"publication_identifier":{"issn":["2041-1723"]},"publication_status":"published","file":[{"creator":"dernst","date_updated":"2022-08-26T11:51:40Z","file_size":5910357,"date_created":"2022-08-26T11:51:40Z","file_name":"2022_NatureCommunications_BenSimon.pdf","access_level":"open_access","relation":"main_file","content_type":"application/pdf","file_id":"11990","checksum":"405936d9e4d33625d80c093c9713a91f","success":1}],"language":[{"iso":"eng"}],"volume":13,"ec_funded":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"SSU"}],"abstract":[{"lang":"eng","text":"The mammalian hippocampal formation (HF) plays a key role in several higher brain functions, such as spatial coding, learning and memory. Its simple circuit architecture is often viewed as a trisynaptic loop, processing input originating from the superficial layers of the entorhinal cortex (EC) and sending it back to its deeper layers. Here, we show that excitatory neurons in layer 6b of the mouse EC project to all sub-regions comprising the HF and receive input from the CA1, thalamus and claustrum. Furthermore, their output is characterized by unique slow-decaying excitatory postsynaptic currents capable of driving plateau-like potentials in their postsynaptic targets. Optogenetic inhibition of the EC-6b pathway affects spatial coding in CA1 pyramidal neurons, while cell ablation impairs not only acquisition of new spatial memories, but also degradation of previously acquired ones. Our results provide evidence of a functional role for cortical layer 6b neurons in the adult brain."}],"oa_version":"Published Version","month":"08","intvolume":" 13","citation":{"mla":"Ben Simon, Yoav, et al. “A Direct Excitatory Projection from Entorhinal Layer 6b Neurons to the Hippocampus Contributes to Spatial Coding and Memory.” Nature Communications, vol. 13, 4826, Springer Nature, 2022, doi:10.1038/s41467-022-32559-8.","short":"Y. Ben Simon, K. Käfer, P. Velicky, J.L. Csicsvari, J.G. Danzl, P.M. Jonas, Nature Communications 13 (2022).","ieee":"Y. Ben Simon, K. Käfer, P. Velicky, J. L. Csicsvari, J. G. Danzl, and P. M. Jonas, “A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory,” Nature Communications, vol. 13. Springer Nature, 2022.","apa":"Ben Simon, Y., Käfer, K., Velicky, P., Csicsvari, J. L., Danzl, J. G., & Jonas, P. M. (2022). A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-32559-8","ama":"Ben Simon Y, Käfer K, Velicky P, Csicsvari JL, Danzl JG, Jonas PM. A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory. Nature Communications. 2022;13. doi:10.1038/s41467-022-32559-8","chicago":"Ben Simon, Yoav, Karola Käfer, Philipp Velicky, Jozsef L Csicsvari, Johann G Danzl, and Peter M Jonas. “A Direct Excitatory Projection from Entorhinal Layer 6b Neurons to the Hippocampus Contributes to Spatial Coding and Memory.” Nature Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-32559-8.","ista":"Ben Simon Y, Käfer K, Velicky P, Csicsvari JL, Danzl JG, Jonas PM. 2022. A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory. Nature Communications. 13, 4826."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"full_name":"Ben Simon, Yoav","last_name":"Ben Simon","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","first_name":"Yoav"},{"last_name":"Käfer","full_name":"Käfer, Karola","id":"2DAA49AA-F248-11E8-B48F-1D18A9856A87","first_name":"Karola"},{"orcid":"0000-0002-2340-7431","full_name":"Velicky, Philipp","last_name":"Velicky","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","first_name":"Philipp"},{"last_name":"Csicsvari","orcid":"0000-0002-5193-4036","full_name":"Csicsvari, Jozsef L","first_name":"Jozsef L","id":"3FA14672-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","last_name":"Danzl"},{"first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas"}],"article_processing_charge":"No","external_id":{"isi":["000841396400008"]},"title":"A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory","article_number":"4826","project":[{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692"},{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Z00312","name":"The Wittgenstein Prize"}],"isi":1,"has_accepted_license":"1","year":"2022","day":"16","publication":"Nature Communications","doi":"10.1038/s41467-022-32559-8","date_published":"2022-08-16T00:00:00Z","date_created":"2022-08-24T08:25:50Z","acknowledgement":"We thank F. Marr and A. Schlögl for technical assistance, E. Kralli-Beller for manuscript editing, as well as C. Sommer and the Imaging and Optics Facility of the Institute of Science and Technology Austria (ISTA) for image analysis scripts and microscopy support. We extend our gratitude to J. Wallenschus and D. Rangel Guerrero for technical assistance acquiring single-unit data and I. Gridchyn for help with single-unit clustering. Finally, we also thank B. Suter for discussions, A. Saunders, M. Jösch, and H. Monyer for critically reading earlier versions of the manuscript, C. Petersen for sharing clearing protocols, and the Scientific Service Units of ISTA for efficient support. 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 to P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award for P.J. and I3600-B27 for J.G.D. and P.V.).","publisher":"Springer Nature","quality_controlled":"1","oa":1},{"tmp":{"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)","short":"CC BY (4.0)"},"article_type":"original","type":"journal_article","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"status":"public","_id":"12288","file_date_updated":"2023-01-30T11:50:53Z","department":[{"_id":"MaJö"},{"_id":"PeJo"}],"date_updated":"2023-08-04T10:29:48Z","ddc":["570"],"scopus_import":"1","intvolume":" 11","month":"09","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."}],"oa_version":"Published Version","pmid":1,"ec_funded":1,"volume":11,"publication_status":"published","publication_identifier":{"eissn":["2050-084X"]},"language":[{"iso":"eng"}],"file":[{"success":1,"checksum":"5a2a65e3e7225090c3d8199f3bbd7b7b","file_id":"12463","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_name":"2022_eLife_Sumser.pdf","date_created":"2023-01-30T11:50:53Z","file_size":8506811,"date_updated":"2023-01-30T11:50:53Z","creator":"dernst"}],"project":[{"grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"call_identifier":"H2020","_id":"2634E9D2-B435-11E9-9278-68D0E5697425","grant_number":"756502","name":"Circuits of Visual Attention"},{"name":"The Wittgenstein Prize","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"name":"Neuronal networks of salience and spatial detection in the murine superior colliculus","grant_number":"LT000256","_id":"266D407A-B435-11E9-9278-68D0E5697425"},{"grant_number":"ALTF 1098-2017","name":"Connecting sensory with motor processing in the superior colliculus","_id":"264FEA02-B435-11E9-9278-68D0E5697425"}],"article_number":"79848","article_processing_charge":"No","external_id":{"isi":["000892204300001"],"pmid":["36040301"]},"author":[{"first_name":"Anton L","id":"3320A096-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4792-1881","full_name":"Sumser, Anton L","last_name":"Sumser"},{"last_name":"Jösch","full_name":"Jösch, Maximilian A","orcid":"0000-0002-3937-1330","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","first_name":"Maximilian A"},{"orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"id":"43DF3136-F248-11E8-B48F-1D18A9856A87","first_name":"Yoav","full_name":"Ben Simon, Yoav","last_name":"Ben Simon"}],"title":"Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling","citation":{"mla":"Sumser, Anton L., et al. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” ELife, vol. 11, 79848, eLife Sciences Publications, 2022, doi:10.7554/elife.79848.","apa":"Sumser, A. L., Jösch, M. A., Jonas, P. M., & Ben Simon, Y. (2022). Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.79848","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. eLife. 2022;11. doi:10.7554/elife.79848","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,” eLife, vol. 11. eLife Sciences Publications, 2022.","short":"A.L. Sumser, M.A. Jösch, P.M. Jonas, Y. Ben Simon, ELife 11 (2022).","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.” ELife. eLife Sciences Publications, 2022. https://doi.org/10.7554/elife.79848.","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."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa":1,"publisher":"eLife Sciences Publications","quality_controlled":"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).","date_created":"2023-01-16T10:04:15Z","date_published":"2022-09-15T00:00:00Z","doi":"10.7554/elife.79848","year":"2022","has_accepted_license":"1","isi":1,"publication":"eLife","day":"15"},{"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","citation":{"mla":"Kim, Olena. Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:11196.","ieee":"O. Kim, “Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses,” Institute of Science and Technology Austria, 2022.","short":"O. Kim, Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses, Institute of Science and Technology Austria, 2022.","ama":"Kim O. Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses. 2022. doi:10.15479/at:ista:11196","apa":"Kim, O. (2022). Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:11196","chicago":"Kim, Olena. “Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:11196.","ista":"Kim O. 2022. Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses. Institute of Science and Technology Austria."},"title":"Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses","author":[{"full_name":"Kim, Olena","last_name":"Kim","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","first_name":"Olena"}],"article_processing_charge":"No","project":[{"_id":"25BAF7B2-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"708497","name":"Presynaptic calcium channels distribution and impact on coupling at the hippocampal mossy fiber synapse"},{"grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"name":"Zellkommunikation in Gesundheit und Krankheit","grant_number":"W01205","call_identifier":"FWF","_id":"25C3DBB6-B435-11E9-9278-68D0E5697425"},{"name":"The Wittgenstein Prize","grant_number":"Z00312","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425"}],"day":"20","has_accepted_license":"1","year":"2022","doi":"10.15479/at:ista:11196","date_published":"2022-04-20T00:00:00Z","date_created":"2022-04-20T09:47:12Z","page":"132","publisher":"Institute of Science and Technology Austria","oa":1,"ddc":["570"],"supervisor":[{"last_name":"Jonas","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M"}],"date_updated":"2023-08-18T06:31:52Z","department":[{"_id":"PeJo"},{"_id":"GradSch"}],"file_date_updated":"2023-04-20T22:30:03Z","_id":"11196","status":"public","type":"dissertation","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"file":[{"date_updated":"2023-04-20T22:30:03Z","file_size":21273537,"creator":"okim","date_created":"2022-04-20T14:21:56Z","file_name":"Olena_KIM_thesis_final.pdf","content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"1616a8bf6f13a57c892dac873dcd0936","file_id":"11220","embargo":"2023-04-19"},{"access_level":"closed","relation":"source_file","content_type":"application/x-zip-compressed","embargo_to":"open_access","checksum":"1acb433f98dc42abb0b4b0cbb0c4b918","file_id":"11221","creator":"okim","date_updated":"2023-04-20T22:30:03Z","file_size":59248569,"date_created":"2022-04-20T14:22:56Z","file_name":"KIM_thesis_final.zip"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2663-337X"]},"degree_awarded":"PhD","publication_status":"published","related_material":{"record":[{"relation":"part_of_dissertation","id":"11222","status":"public"},{"relation":"part_of_dissertation","status":"public","id":"7473"}]},"ec_funded":1,"oa_version":"Published Version","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"PreCl"}],"abstract":[{"lang":"eng","text":"One of the fundamental questions in Neuroscience is how the structure of synapses and their physiological properties are related. While synaptic transmission remains a dynamic process, electron microscopy provides images with comparably low temporal resolution (Studer et al., 2014). The current work overcomes this challenge and describes an improved “Flash and Freeze” technique (Watanabe et al., 2013a; Watanabe et al., 2013b) to study synaptic transmission at the hippocampal mossy fiber-CA3 pyramidal neuron synapses, using mouse acute brain slices and organotypic slices culture. The improved method allowed for selective stimulation of presynaptic mossy fiber boutons and the observation of synaptic vesicle pool dynamics at the active zones. Our results uncovered several intriguing morphological features of mossy fiber boutons. First, the docked vesicle pool was largely depleted (more than 70%) after stimulation, implying that the docked synaptic vesicles pool and readily releasable pool are vastly overlapping in mossy fiber boutons. Second, the synaptic vesicles are skewed towards larger diameters, displaying a wide range of sizes. An increase in the mean diameter of synaptic vesicles, after single and repetitive stimulation, suggests that smaller vesicles have a higher release probability. Third, we observed putative endocytotic structures after moderate light stimulation, matching the timing of previously described ultrafast endocytosis (Watanabe et al., 2013a; Delvendahl et al., 2016). \r\n\tIn addition, synaptic transmission depends on a sophisticated system of protein machinery and calcium channels (Südhof, 2013b), which amplifies the challenge in studying synaptic communication as these interactions can be potentially modified during synaptic plasticity. And although recent study elucidated the potential correlation between physiological and morphological properties of synapses during synaptic plasticity (Vandael et al., 2020), the molecular underpinning of it remains unknown. Thus, the presented work tries to overcome this challenge and aims to pinpoint changes in the molecular architecture at hippocampal mossy fiber bouton synapses during short- and long-term potentiation (STP and LTP), we combined chemical potentiation, with the application of a cyclic adenosine monophosphate agonist (i.e. forskolin) and freeze-fracture replica immunolabelling. This method allowed the localization of membrane-bound proteins with nanometer precision within the active zone, in particular, P/Q-type calcium channels and synaptic vesicle priming proteins Munc13-1/2. First, we found that the number of clusters of Munc13-1 in the mossy fiber bouton active zone increased significantly during STP, but decreased to lower than the control value during LTP. Secondly, although the distance between the calcium channels and Munc13-1s did not change after induction of STP, it shortened during the LTP phase. Additionally, forskolin did not affect Munc13-2 distribution during STP and LTP. These results indicate the existence of two distinct mechanisms that govern STP and LTP at mossy fiber bouton synapses: an increase in the readily realizable pool in the case of STP and a potential increase in release probability during LTP. “Flash and freeze” and functional electron microscopy, are versatile methods that can be successfully applied to intact brain circuits to study synaptic transmission even at the molecular level.\r\n"}],"month":"04","alternative_title":["ISTA Thesis"]},{"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2022.03.16.484431"}],"oa":1,"publisher":"Cold Spring Harbor Laboratory","month":"05","abstract":[{"lang":"eng","text":"Complex wiring between neurons underlies the information-processing network enabling all brain functions, including cognition and memory. For understanding how the network is structured, processes information, and changes over time, comprehensive visualization of the architecture of living brain tissue with its cellular and molecular components would open up major opportunities. However, electron microscopy (EM) provides nanometre-scale resolution required for full in-silico reconstruction1–5, yet is limited to fixed specimens and static representations. Light microscopy allows live observation, with super-resolution approaches6–12 facilitating nanoscale visualization, but comprehensive 3D-reconstruction of living brain tissue has been hindered by tissue photo-burden, photobleaching, insufficient 3D-resolution, and inadequate signal-to-noise ratio (SNR). Here we demonstrate saturated reconstruction of living brain tissue. We developed an integrated imaging and analysis technology, adapting stimulated emission depletion (STED) microscopy6,13 in extracellularly labelled tissue14 for high SNR and near-isotropic resolution. Centrally, a two-stage deep-learning approach leveraged previously obtained information on sample structure to drastically reduce photo-burden and enable automated volumetric reconstruction down to single synapse level. Live reconstruction provides unbiased analysis of tissue architecture across time in relation to functional activity and targeted activation, and contextual understanding of molecular labelling. This adoptable technology will facilitate novel insights into the dynamic functional architecture of living brain tissue."}],"oa_version":"Preprint","date_created":"2022-08-23T11:07:59Z","doi":"10.1101/2022.03.16.484431","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"12470"}]},"date_published":"2022-05-09T00:00:00Z","publication_status":"submitted","year":"2022","language":[{"iso":"eng"}],"publication":"bioRxiv","day":"09","type":"preprint","status":"public","_id":"11943","article_processing_charge":"No","author":[{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","first_name":"Philipp","full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431","last_name":"Velicky"},{"orcid":"0000-0001-5665-0430","full_name":"Miguel Villalba, Eder","last_name":"Miguel Villalba","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","first_name":"Eder"},{"orcid":"0000-0003-3862-1235","full_name":"Michalska, Julia M","last_name":"Michalska","first_name":"Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Donglai","last_name":"Wei","full_name":"Wei, Donglai"},{"full_name":"Lin, Zudi","last_name":"Lin","first_name":"Zudi"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake","last_name":"Watson","orcid":"0000-0002-8698-3823","full_name":"Watson, Jake"},{"last_name":"Troidl","full_name":"Troidl, Jakob","first_name":"Jakob"},{"first_name":"Johanna","full_name":"Beyer, Johanna","last_name":"Beyer"},{"full_name":"Ben Simon, Yoav","last_name":"Ben Simon","first_name":"Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","last_name":"Sommer","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Jahr, Wiebke","last_name":"Jahr","first_name":"Wiebke","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","full_name":"Cenameri, Alban","last_name":"Cenameri"},{"first_name":"Johannes","last_name":"Broichhagen","full_name":"Broichhagen, Johannes"},{"first_name":"Seth G. N.","full_name":"Grant, Seth G. N.","last_name":"Grant"},{"orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M"},{"last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"},{"first_name":"Hanspeter","last_name":"Pfister","full_name":"Pfister, Hanspeter"},{"orcid":"0000-0001-6511-9385","full_name":"Bickel, Bernd","last_name":"Bickel","id":"49876194-F248-11E8-B48F-1D18A9856A87","first_name":"Bernd"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","last_name":"Danzl"}],"department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"}],"title":"Saturated reconstruction of living brain tissue","citation":{"ista":"Velicky P, Miguel Villalba E, Michalska JM, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. Saturated reconstruction of living brain tissue. bioRxiv, 10.1101/2022.03.16.484431.","chicago":"Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Donglai Wei, Zudi Lin, Jake Watson, Jakob Troidl, et al. “Saturated Reconstruction of Living Brain Tissue.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2022.03.16.484431.","short":"P. Velicky, E. Miguel Villalba, J.M. Michalska, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, BioRxiv (n.d.).","ieee":"P. Velicky et al., “Saturated reconstruction of living brain tissue,” bioRxiv. Cold Spring Harbor Laboratory.","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction of living brain tissue. bioRxiv. doi:10.1101/2022.03.16.484431","apa":"Velicky, P., Miguel Villalba, E., Michalska, J. M., Wei, D., Lin, Z., Watson, J., … Danzl, J. G. (n.d.). Saturated reconstruction of living brain tissue. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.03.16.484431","mla":"Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2022.03.16.484431."},"date_updated":"2024-03-27T23:30:20Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"date_created":"2022-08-24T08:24:52Z","date_published":"2022-08-18T00:00:00Z","doi":"10.1101/2022.08.17.504272","related_material":{"record":[{"relation":"dissertation_contains","id":"12470","status":"public"}]},"publication_status":"submitted","year":"2022","publication":"bioRxiv","language":[{"iso":"eng"}],"day":"18","oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2022.08.17.504272"}],"publisher":"Cold Spring Harbor Laboratory","month":"08","abstract":[{"lang":"eng","text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanoscopic synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS leverages fixation-compatible extracellular labeling and advanced optical readout, in particular stimulated-emission depletion and expansion microscopy, to comprehensively delineate cellular structures. It enables 3D-reconstructing single synapses and mapping synaptic connectivity by identification and tailored analysis of putative synaptic cleft regions. Applying CATS to the hippocampal mossy fiber circuitry, we demonstrate its power to reveal the system’s molecularly informed ultrastructure across spatial scales and assess local connectivity by reconstructing and quantifying the synaptic input and output structure of identified neurons."}],"oa_version":"Preprint","article_processing_charge":"No","author":[{"orcid":"0000-0003-3862-1235","full_name":"Michalska, Julia M","last_name":"Michalska","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","first_name":"Julia M"},{"first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia","last_name":"Lyudchik"},{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","first_name":"Philipp","last_name":"Velicky","full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431"},{"id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","first_name":"Hana","full_name":"Korinkova, Hana","last_name":"Korinkova"},{"full_name":"Watson, Jake","orcid":"0000-0002-8698-3823","last_name":"Watson","id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban","last_name":"Cenameri","full_name":"Cenameri, Alban"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M","last_name":"Sommer","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105"},{"id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","first_name":"Alessandro","full_name":"Venturino, Alessandro","orcid":"0000-0003-2356-9403","last_name":"Venturino"},{"last_name":"Roessler","full_name":"Roessler, Karl","first_name":"Karl"},{"first_name":"Thomas","last_name":"Czech","full_name":"Czech, Thomas"},{"orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra","last_name":"Siegert","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"},{"orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G"}],"title":"Uncovering brain tissue architecture across scales with super-resolution light microscopy","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"}],"date_updated":"2024-03-27T23:30:20Z","citation":{"ama":"Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv. doi:10.1101/2022.08.17.504272","apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.08.17.504272","ieee":"J. M. Michalska et al., “Uncovering brain tissue architecture across scales with super-resolution light microscopy,” bioRxiv. Cold Spring Harbor Laboratory.","short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, A. Venturino, K. Roessler, T. Czech, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, BioRxiv (n.d.).","mla":"Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2022.08.17.504272.","ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv, 10.1101/2022.08.17.504272.","chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2022.08.17.504272."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","type":"preprint","status":"public","_id":"11950"},{"article_number":"2204","article_processing_charge":"No","author":[{"full_name":"Pandey, Rakesh","last_name":"Pandey","first_name":"Rakesh"},{"first_name":"Yusur","last_name":"Al-Nuaimi","full_name":"Al-Nuaimi, Yusur"},{"first_name":"Rajiv Kumar","id":"46CB58F2-F248-11E8-B48F-1D18A9856A87","last_name":"Mishra","full_name":"Mishra, Rajiv Kumar"},{"last_name":"Spurgeon","full_name":"Spurgeon, Sarah K.","first_name":"Sarah K."},{"last_name":"Goodfellow","full_name":"Goodfellow, Marc","first_name":"Marc"}],"title":"Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis","citation":{"mla":"Pandey, Rakesh, et al. “Role of Subnetworks Mediated by TNF α, IL-23/IL-17 and IL-15 in a Network Involved in the Pathogenesis of Psoriasis.” Scientific Reports, vol. 11, 2204, Springer Nature, 2021, doi:10.1038/s41598-020-80507-7.","ama":"Pandey R, Al-Nuaimi Y, Mishra RK, Spurgeon SK, Goodfellow M. Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis. Scientific Reports. 2021;11. doi:10.1038/s41598-020-80507-7","apa":"Pandey, R., Al-Nuaimi, Y., Mishra, R. K., Spurgeon, S. K., & Goodfellow, M. (2021). Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis. Scientific Reports. Springer Nature. https://doi.org/10.1038/s41598-020-80507-7","ieee":"R. Pandey, Y. Al-Nuaimi, R. K. Mishra, S. K. Spurgeon, and M. Goodfellow, “Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis,” Scientific Reports, vol. 11. Springer Nature, 2021.","short":"R. Pandey, Y. Al-Nuaimi, R.K. Mishra, S.K. Spurgeon, M. Goodfellow, Scientific Reports 11 (2021).","chicago":"Pandey, Rakesh, Yusur Al-Nuaimi, Rajiv Kumar Mishra, Sarah K. Spurgeon, and Marc Goodfellow. “Role of Subnetworks Mediated by TNF α, IL-23/IL-17 and IL-15 in a Network Involved in the Pathogenesis of Psoriasis.” Scientific Reports. Springer Nature, 2021. https://doi.org/10.1038/s41598-020-80507-7.","ista":"Pandey R, Al-Nuaimi Y, Mishra RK, Spurgeon SK, Goodfellow M. 2021. Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis. Scientific Reports. 11, 2204."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa":1,"publisher":"Springer Nature","quality_controlled":"1","acknowledgement":"RP acknowledges the Department of Science and Technology, India for the support through the DST-INSPIRE Faculty Award (DST/INSPIRE/04/2015/001939). This work was supported by the Engineering and Physical Sciences Research Council (EPSRC), United Kingdom (Grant numbers EP/J018295/1, EP/J018392/1, EP/N014391/1). The contribution of RP was also supported by the later Grant. This work was generously supported by the Welcome Trust Institutional Strategic Support Award (204909/Z/16/Z) too. The contribution of MG was supported by the EPSRC via EP/N014391/1 and a Wellcome Trust Institutional Strategic Support Award (WT105618MA). The contribution of YA was generously supported by the Wellcome Trust Institutional Strategic Support Award (WT105618MA).","date_created":"2021-02-07T23:01:12Z","doi":"10.1038/s41598-020-80507-7","date_published":"2021-01-26T00:00:00Z","year":"2021","has_accepted_license":"1","publication":"Scientific Reports","day":"26","tmp":{"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)","short":"CC BY (4.0)"},"article_type":"original","type":"journal_article","status":"public","_id":"9097","file_date_updated":"2021-02-09T07:33:23Z","department":[{"_id":"PeJo"}],"date_updated":"2022-08-19T07:22:23Z","ddc":["570"],"scopus_import":"1","intvolume":" 11","month":"01","abstract":[{"text":"Psoriasis is a chronic inflammatory skin disease clinically characterized by the appearance of red colored, well-demarcated plaques with thickened skin and with silvery scales. Recent studies have established the involvement of a complex signalling network of interactions between cytokines, immune cells and skin cells called keratinocytes. Keratinocytes form the cells of the outermost layer of the skin (epidermis). Visible plaques in psoriasis are developed due to the fast proliferation and unusual differentiation of keratinocyte cells. Despite that, the exact mechanism of the appearance of these plaques in the cytokine-immune cell network is not clear. A mathematical model embodying interactions between key immune cells believed to be involved in psoriasis, keratinocytes and relevant cytokines has been developed. The complex network formed of these interactions poses several challenges. Here, we choose to study subnetworks of this complex network and initially focus on interactions involving TNFα, IL-23/IL-17, and IL-15. These are chosen based on known evidence of their therapeutic efficacy. In addition, we explore the role of IL-15 in the pathogenesis of psoriasis and its potential as a future drug target for a novel treatment option. We perform steady state analyses for these subnetworks and demonstrate that the interactions between cells, driven by cytokines could cause the emergence of a psoriasis state (hyper-proliferation of keratinocytes) when levels of TNFα, IL-23/IL-17 or IL-15 are increased. The model results explain and support the clinical potentiality of anti-cytokine treatments. Interestingly, our results suggest different dynamic scenarios underpin the pathogenesis of psoriasis, depending upon the dominant cytokines of subnetworks. We observed that the increase in the level of IL-23/IL-17 and IL-15 could lead to psoriasis via a bistable route, whereas an increase in the level of TNFα would lead to a monotonic and gradual disease progression. Further, we demonstrate how this insight, bistability, could be exploited to improve the current therapies and develop novel treatment strategies for psoriasis.","lang":"eng"}],"oa_version":"Published Version","volume":11,"publication_status":"published","publication_identifier":{"eissn":["20452322"]},"language":[{"iso":"eng"}],"file":[{"creator":"dernst","file_size":2885056,"date_updated":"2021-02-09T07:33:23Z","file_name":"2021_ScientificReports_Pandey.pdf","date_created":"2021-02-09T07:33:23Z","relation":"main_file","access_level":"open_access","content_type":"application/pdf","success":1,"file_id":"9106","checksum":"e8a68df48750712671f5c47b0228e531"}]},{"oa_version":"Published Version","abstract":[{"text":"Background: To understand information coding in single neurons, it is necessary to analyze subthreshold synaptic events, action potentials (APs), and their interrelation in different behavioral states. However, detecting excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) in behaving animals remains challenging, because of unfavorable signal-to-noise ratio, high frequency, fluctuating amplitude, and variable time course of synaptic events.\r\nNew method: We developed a method for synaptic event detection, termed MOD (Machine-learning Optimal-filtering Detection-procedure), which combines concepts of supervised machine learning and optimal Wiener filtering. Experts were asked to manually score short epochs of data. The algorithm was trained to obtain the optimal filter coefficients of a Wiener filter and the optimal detection threshold. Scored and unscored data were then processed with the optimal filter, and events were detected as peaks above threshold.\r\nResults: We challenged MOD with EPSP traces in vivo in mice during spatial navigation and EPSC traces in vitro in slices under conditions of enhanced transmitter release. The area under the curve (AUC) of the receiver operating characteristics (ROC) curve was, on average, 0.894 for in vivo and 0.969 for in vitro data sets, indicating high detection accuracy and efficiency.\r\nComparison with existing methods: When benchmarked using a (1 − AUC)−1 metric, MOD outperformed previous methods (template-fit, deconvolution, and Bayesian methods) by an average factor of 3.13 for in vivo data sets, but showed comparable (template-fit, deconvolution) or higher (Bayesian) computational efficacy.\r\nConclusions: MOD may become an important new tool for large-scale, real-time analysis of synaptic activity.","lang":"eng"}],"acknowledged_ssus":[{"_id":"SSU"}],"month":"03","intvolume":" 357","scopus_import":"1","file":[{"file_id":"9339","checksum":"2a5800d91b96d08b525e17319dcd5e44","success":1,"access_level":"open_access","relation":"main_file","content_type":"application/pdf","date_created":"2021-04-19T08:30:22Z","file_name":"2021_JourNeuroscienceMeth_Zhang.pdf","creator":"dernst","date_updated":"2021-04-19T08:30:22Z","file_size":6924738}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["0165-0270"],"eissn":["1872-678X"]},"publication_status":"published","volume":357,"issue":"6","ec_funded":1,"_id":"9329","status":"public","article_type":"original","type":"journal_article","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"ddc":["570"],"date_updated":"2023-08-07T14:36:14Z","department":[{"_id":"PeJo"},{"_id":"ScienComp"}],"file_date_updated":"2021-04-19T08:30:22Z","acknowledgement":"This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement number 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award to P.J.). We thank Drs. Jozsef Csicsvari, Christoph Lampert, and Federico Stella for critically reading previous manuscript versions. We are also grateful to Drs. Josh Merel and Ben Shababo for their help with applying the Bayesian detection method to our data. We also thank Florian Marr for technical assistance, Eleftheria Kralli-Beller for manuscript editing, and the Scientific Service Units of IST Austria for efficient support.","publisher":"Elsevier","quality_controlled":"1","oa":1,"day":"09","publication":"Journal of Neuroscience Methods","isi":1,"has_accepted_license":"1","year":"2021","doi":"10.1016/j.jneumeth.2021.109125","date_published":"2021-03-09T00:00:00Z","date_created":"2021-04-18T22:01:39Z","article_number":"109125","project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692"},{"name":"The Wittgenstein Prize","grant_number":"Z00312","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"ama":"Zhang X, Schlögl A, Vandael DH, Jonas PM. MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo. Journal of Neuroscience Methods. 2021;357(6). doi:10.1016/j.jneumeth.2021.109125","apa":"Zhang, X., Schlögl, A., Vandael, D. H., & Jonas, P. M. (2021). MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo. Journal of Neuroscience Methods. Elsevier. https://doi.org/10.1016/j.jneumeth.2021.109125","short":"X. Zhang, A. Schlögl, D.H. Vandael, P.M. Jonas, Journal of Neuroscience Methods 357 (2021).","ieee":"X. Zhang, A. Schlögl, D. H. Vandael, and P. M. Jonas, “MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo,” Journal of Neuroscience Methods, vol. 357, no. 6. Elsevier, 2021.","mla":"Zhang, Xiaomin, et al. “MOD: A Novel Machine-Learning Optimal-Filtering Method for Accurate and Efficient Detection of Subthreshold Synaptic Events in Vivo.” Journal of Neuroscience Methods, vol. 357, no. 6, 109125, Elsevier, 2021, doi:10.1016/j.jneumeth.2021.109125.","ista":"Zhang X, Schlögl A, Vandael DH, Jonas PM. 2021. MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo. Journal of Neuroscience Methods. 357(6), 109125.","chicago":"Zhang, Xiaomin, Alois Schlögl, David H Vandael, and Peter M Jonas. “MOD: A Novel Machine-Learning Optimal-Filtering Method for Accurate and Efficient Detection of Subthreshold Synaptic Events in Vivo.” Journal of Neuroscience Methods. Elsevier, 2021. https://doi.org/10.1016/j.jneumeth.2021.109125."},"title":"MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo","author":[{"last_name":"Zhang","full_name":"Zhang, Xiaomin","id":"423EC9C2-F248-11E8-B48F-1D18A9856A87","first_name":"Xiaomin"},{"id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","first_name":"Alois","orcid":"0000-0002-5621-8100","full_name":"Schlögl, Alois","last_name":"Schlögl"},{"first_name":"David H","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","last_name":"Vandael","full_name":"Vandael, David H","orcid":"0000-0001-7577-1676"},{"full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M"}],"external_id":{"isi":["000661088500005"]},"article_processing_charge":"Yes (via OA deal)"}]