[{"related_material":{"record":[{"status":"public","id":"11222","relation":"part_of_dissertation"},{"relation":"part_of_dissertation","status":"public","id":"7473"}]},"ec_funded":1,"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","publication_identifier":{"issn":["2663-337X"]},"publication_status":"published","degree_awarded":"PhD","file":[{"content_type":"application/pdf","relation":"main_file","access_level":"open_access","embargo":"2023-04-19","checksum":"1616a8bf6f13a57c892dac873dcd0936","file_id":"11220","file_size":21273537,"date_updated":"2023-04-20T22:30:03Z","creator":"okim","file_name":"Olena_KIM_thesis_final.pdf","date_created":"2022-04-20T14:21:56Z"},{"file_name":"KIM_thesis_final.zip","date_created":"2022-04-20T14:22:56Z","creator":"okim","file_size":59248569,"date_updated":"2023-04-20T22:30:03Z","checksum":"1acb433f98dc42abb0b4b0cbb0c4b918","file_id":"11221","relation":"source_file","access_level":"closed","embargo_to":"open_access","content_type":"application/x-zip-compressed"}],"language":[{"iso":"eng"}],"alternative_title":["ISTA Thesis"],"month":"04","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"}],"oa_version":"Published Version","department":[{"_id":"PeJo"},{"_id":"GradSch"}],"file_date_updated":"2023-04-20T22:30:03Z","supervisor":[{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","last_name":"Jonas","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M"}],"date_updated":"2023-08-18T06:31:52Z","ddc":["570"],"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"},"status":"public","_id":"11196","page":"132","date_published":"2022-04-20T00:00:00Z","doi":"10.15479/at:ista:11196","date_created":"2022-04-20T09:47:12Z","has_accepted_license":"1","year":"2022","day":"20","publisher":"Institute of Science and Technology Austria","oa":1,"author":[{"first_name":"Olena","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","full_name":"Kim, Olena","last_name":"Kim"}],"article_processing_charge":"No","title":"Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses","citation":{"short":"O. Kim, Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron Synapses, Institute of Science and Technology Austria, 2022.","ieee":"O. Kim, “Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses,” Institute of Science and Technology Austria, 2022.","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","ama":"Kim O. Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses. 2022. doi:10.15479/at:ista:11196","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.","ista":"Kim O. 2022. Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses. Institute of Science and Technology Austria.","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."},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","project":[{"call_identifier":"H2020","_id":"25BAF7B2-B435-11E9-9278-68D0E5697425","grant_number":"708497","name":"Presynaptic calcium channels distribution and impact on coupling at the hippocampal mossy fiber synapse"},{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692"},{"call_identifier":"FWF","_id":"25C3DBB6-B435-11E9-9278-68D0E5697425","name":"Zellkommunikation in Gesundheit und Krankheit","grant_number":"W01205"},{"grant_number":"Z00312","name":"The Wittgenstein Prize","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}]},{"citation":{"mla":"Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.” BioRxiv, Cold Spring Harbor Laboratory, doi: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","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.","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."},"date_updated":"2024-03-27T23:30:20Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","author":[{"last_name":"Velicky","orcid":"0000-0002-2340-7431","full_name":"Velicky, Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","first_name":"Philipp"},{"id":"3FB91342-F248-11E8-B48F-1D18A9856A87","first_name":"Eder","last_name":"Miguel Villalba","orcid":"0000-0001-5665-0430","full_name":"Miguel Villalba, Eder"},{"first_name":"Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235","last_name":"Michalska"},{"first_name":"Donglai","last_name":"Wei","full_name":"Wei, Donglai"},{"last_name":"Lin","full_name":"Lin, Zudi","first_name":"Zudi"},{"full_name":"Watson, Jake","orcid":"0000-0002-8698-3823","last_name":"Watson","id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake"},{"full_name":"Troidl, Jakob","last_name":"Troidl","first_name":"Jakob"},{"first_name":"Johanna","last_name":"Beyer","full_name":"Beyer, Johanna"},{"first_name":"Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","last_name":"Ben Simon","full_name":"Ben Simon, Yoav"},{"last_name":"Sommer","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Jahr","full_name":"Jahr, Wiebke","first_name":"Wiebke","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Cenameri, Alban","last_name":"Cenameri","first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"first_name":"Johannes","last_name":"Broichhagen","full_name":"Broichhagen, Johannes"},{"first_name":"Seth G. N.","last_name":"Grant","full_name":"Grant, Seth G. N."},{"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":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178"},{"first_name":"Hanspeter","last_name":"Pfister","full_name":"Pfister, Hanspeter"},{"id":"49876194-F248-11E8-B48F-1D18A9856A87","first_name":"Bernd","last_name":"Bickel","full_name":"Bickel, Bernd","orcid":"0000-0001-6511-9385"},{"last_name":"Danzl","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"}],"title":"Saturated reconstruction of living brain tissue","department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"}],"_id":"11943","type":"preprint","status":"public","year":"2022","publication_status":"submitted","language":[{"iso":"eng"}],"publication":"bioRxiv","day":"09","date_created":"2022-08-23T11:07:59Z","doi":"10.1101/2022.03.16.484431","related_material":{"record":[{"status":"public","id":"12470","relation":"dissertation_contains"}]},"date_published":"2022-05-09T00:00:00Z","abstract":[{"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.","lang":"eng"}],"oa_version":"Preprint","oa":1,"main_file_link":[{"url":"https://doi.org/10.1101/2022.03.16.484431","open_access":"1"}],"publisher":"Cold Spring Harbor Laboratory","month":"05"},{"doi":"10.1101/2022.08.17.504272","related_material":{"record":[{"status":"public","id":"12470","relation":"dissertation_contains"}]},"date_published":"2022-08-18T00:00:00Z","date_created":"2022-08-24T08:24:52Z","publication_status":"submitted","year":"2022","day":"18","language":[{"iso":"eng"}],"publication":"bioRxiv","publisher":"Cold Spring Harbor Laboratory","oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2022.08.17.504272"}],"month":"08","abstract":[{"text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to 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.","lang":"eng"}],"oa_version":"Preprint","author":[{"last_name":"Michalska","full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","first_name":"Julia M"},{"full_name":"Lyudchik, Julia","last_name":"Lyudchik","first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","first_name":"Philipp","orcid":"0000-0002-2340-7431","full_name":"Velicky, Philipp","last_name":"Velicky"},{"full_name":"Korinkova, Hana","last_name":"Korinkova","first_name":"Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake","orcid":"0000-0002-8698-3823","full_name":"Watson, Jake","last_name":"Watson"},{"full_name":"Cenameri, Alban","last_name":"Cenameri","first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","last_name":"Sommer","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Venturino","orcid":"0000-0003-2356-9403","full_name":"Venturino, Alessandro","first_name":"Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Karl","last_name":"Roessler","full_name":"Roessler, Karl"},{"first_name":"Thomas","full_name":"Czech, Thomas","last_name":"Czech"},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra","last_name":"Siegert","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877"},{"orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas"},{"first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","last_name":"Danzl"}],"article_processing_charge":"No","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"}],"title":"Uncovering brain tissue architecture across scales with super-resolution light microscopy","citation":{"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.","ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv, 10.1101/2022.08.17.504272.","mla":"Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2022.08.17.504272.","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","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","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.)."},"date_updated":"2024-03-27T23:30:20Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","type":"preprint","status":"public","_id":"11950"},{"title":"Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis","author":[{"full_name":"Pandey, Rakesh","last_name":"Pandey","first_name":"Rakesh"},{"last_name":"Al-Nuaimi","full_name":"Al-Nuaimi, Yusur","first_name":"Yusur"},{"id":"46CB58F2-F248-11E8-B48F-1D18A9856A87","first_name":"Rajiv Kumar","last_name":"Mishra","full_name":"Mishra, Rajiv Kumar"},{"first_name":"Sarah K.","full_name":"Spurgeon, Sarah K.","last_name":"Spurgeon"},{"last_name":"Goodfellow","full_name":"Goodfellow, Marc","first_name":"Marc"}],"article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"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.","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.","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).","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","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","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."},"article_number":"2204","date_published":"2021-01-26T00:00:00Z","doi":"10.1038/s41598-020-80507-7","date_created":"2021-02-07T23:01:12Z","day":"26","publication":"Scientific Reports","has_accepted_license":"1","year":"2021","publisher":"Springer Nature","quality_controlled":"1","oa":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).","file_date_updated":"2021-02-09T07:33:23Z","department":[{"_id":"PeJo"}],"ddc":["570"],"date_updated":"2022-08-19T07:22:23Z","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":"9097","volume":11,"file":[{"file_size":2885056,"date_updated":"2021-02-09T07:33:23Z","creator":"dernst","file_name":"2021_ScientificReports_Pandey.pdf","date_created":"2021-02-09T07:33:23Z","content_type":"application/pdf","relation":"main_file","access_level":"open_access","success":1,"checksum":"e8a68df48750712671f5c47b0228e531","file_id":"9106"}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["20452322"]},"publication_status":"published","month":"01","intvolume":" 11","scopus_import":"1","oa_version":"Published Version","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"}]},{"scopus_import":"1","month":"03","intvolume":" 357","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"}],"oa_version":"Published Version","issue":"6","volume":357,"ec_funded":1,"publication_identifier":{"eissn":["1872-678X"],"issn":["0165-0270"]},"publication_status":"published","file":[{"relation":"main_file","access_level":"open_access","content_type":"application/pdf","success":1,"file_id":"9339","checksum":"2a5800d91b96d08b525e17319dcd5e44","creator":"dernst","file_size":6924738,"date_updated":"2021-04-19T08:30:22Z","file_name":"2021_JourNeuroscienceMeth_Zhang.pdf","date_created":"2021-04-19T08:30:22Z"}],"language":[{"iso":"eng"}],"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"},"status":"public","_id":"9329","file_date_updated":"2021-04-19T08:30:22Z","department":[{"_id":"PeJo"},{"_id":"ScienComp"}],"date_updated":"2023-08-07T14:36:14Z","ddc":["570"],"quality_controlled":"1","publisher":"Elsevier","oa":1,"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.","date_published":"2021-03-09T00:00:00Z","doi":"10.1016/j.jneumeth.2021.109125","date_created":"2021-04-18T22:01:39Z","has_accepted_license":"1","isi":1,"year":"2021","day":"09","publication":"Journal of Neuroscience Methods","project":[{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692"},{"name":"The Wittgenstein Prize","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"article_number":"109125","author":[{"first_name":"Xiaomin","id":"423EC9C2-F248-11E8-B48F-1D18A9856A87","full_name":"Zhang, Xiaomin","last_name":"Zhang"},{"last_name":"Schlögl","orcid":"0000-0002-5621-8100","full_name":"Schlögl, Alois","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","first_name":"Alois"},{"id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","first_name":"David H","last_name":"Vandael","orcid":"0000-0001-7577-1676","full_name":"Vandael, David H"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","last_name":"Jonas","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804"}],"external_id":{"isi":["000661088500005"]},"article_processing_charge":"Yes (via OA deal)","title":"MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo","citation":{"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.","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."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8"},{"acknowledgement":"We thank members of the Greger laboratory, B. Herguedas, J. Krieger and J.-N. Dohrke for comments on the manuscript; J. Krieger and J.-N. Dohrke for discussion, J. Krieger for help with the normal mode analysis, B. Köhegyi for help with cryo-EM imaging, V. Chang and K. Suzuki for helping to generate the CNIH2-1D4-HA stable cell line, M. Carvalho for assistance at early stages of this project, the LMB scientific computing and the cryo-EM facility for support, P. Emsley for help with model building, T. Nakane for helpful comments with RELION 3.1 and R. Warshamanage for helping with EMDA cryo-EM-map processing. We acknowledge the Diamond Light Source for access and support of the Cryo-EM facilities at the UK national electron bio10 imaging centre (eBIC), proposal EM17434, funded by the Wellcome Trust, MRC and BBSRC. This work was supported by grants from the Medical Research Council, as part of United Kingdom Research and Innovation (also known as UK Research and Innovation) (MC_U105174197) and BBSRC (BB/N002113/1) to I.H.G.","publisher":"Springer Nature","quality_controlled":"1","oa":1,"isi":1,"year":"2021","day":"02","publication":"Nature","page":"454-458","doi":"10.1038/s41586-021-03613-0","date_published":"2021-06-02T00:00:00Z","date_created":"2021-06-13T22:01:33Z","citation":{"chicago":"Zhang, Danyang, Jake Watson, Peter M. Matthews, Ondrej Cais, and Ingo H. Greger. “Gating and Modulation of a Hetero-Octameric AMPA Glutamate Receptor.” Nature. Springer Nature, 2021. https://doi.org/10.1038/s41586-021-03613-0.","ista":"Zhang D, Watson J, Matthews PM, Cais O, Greger IH. 2021. Gating and modulation of a hetero-octameric AMPA glutamate receptor. Nature. 594, 454–458.","mla":"Zhang, Danyang, et al. “Gating and Modulation of a Hetero-Octameric AMPA Glutamate Receptor.” Nature, vol. 594, Springer Nature, 2021, pp. 454–58, doi:10.1038/s41586-021-03613-0.","short":"D. Zhang, J. Watson, P.M. Matthews, O. Cais, I.H. Greger, Nature 594 (2021) 454–458.","ieee":"D. Zhang, J. Watson, P. M. Matthews, O. Cais, and I. H. Greger, “Gating and modulation of a hetero-octameric AMPA glutamate receptor,” Nature, vol. 594. Springer Nature, pp. 454–458, 2021.","apa":"Zhang, D., Watson, J., Matthews, P. M., Cais, O., & Greger, I. H. (2021). Gating and modulation of a hetero-octameric AMPA glutamate receptor. Nature. Springer Nature. https://doi.org/10.1038/s41586-021-03613-0","ama":"Zhang D, Watson J, Matthews PM, Cais O, Greger IH. Gating and modulation of a hetero-octameric AMPA glutamate receptor. Nature. 2021;594:454-458. doi:10.1038/s41586-021-03613-0"},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"last_name":"Zhang","full_name":"Zhang, Danyang","first_name":"Danyang"},{"first_name":"Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","last_name":"Watson","orcid":"0000-0002-8698-3823","full_name":"Watson, Jake"},{"full_name":"Matthews, Peter M.","last_name":"Matthews","first_name":"Peter M."},{"first_name":"Ondrej","full_name":"Cais, Ondrej","last_name":"Cais"},{"last_name":"Greger","full_name":"Greger, Ingo H.","first_name":"Ingo H."}],"external_id":{"pmid":["34079129"],"isi":["000657238100003"]},"article_processing_charge":"No","title":"Gating and modulation of a hetero-octameric AMPA glutamate receptor","abstract":[{"lang":"eng","text":"AMPA receptors (AMPARs) mediate the majority of excitatory transmission in the brain and enable the synaptic plasticity that underlies learning1. A diverse array of AMPAR signalling complexes are established by receptor auxiliary subunits, which associate with the AMPAR in various combinations to modulate trafficking, gating and synaptic strength2. However, their mechanisms of action are poorly understood. Here we determine cryo-electron microscopy structures of the heteromeric GluA1–GluA2 receptor assembled with both TARP-γ8 and CNIH2, the predominant AMPAR complex in the forebrain, in both resting and active states. Two TARP-γ8 and two CNIH2 subunits insert at distinct sites beneath the ligand-binding domains of the receptor, with site-specific lipids shaping each interaction and affecting the gating regulation of the AMPARs. Activation of the receptor leads to asymmetry between GluA1 and GluA2 along the ion conduction path and an outward expansion of the channel triggers counter-rotations of both auxiliary subunit pairs, promoting the active-state conformation. In addition, both TARP-γ8 and CNIH2 pivot towards the pore exit upon activation, extending their reach for cytoplasmic receptor elements. CNIH2 achieves this through its uniquely extended M2 helix, which has transformed this endoplasmic reticulum-export factor into a powerful AMPAR modulator that is capable of providing hippocampal pyramidal neurons with their integrative synaptic properties. "}],"oa_version":"Published Version","pmid":1,"scopus_import":"1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1038/s41586-021-03613-0"}],"month":"06","intvolume":" 594","publication_identifier":{"eissn":["1476-4687"],"issn":["0028-0836"]},"publication_status":"published","language":[{"iso":"eng"}],"volume":594,"_id":"9549","article_type":"original","type":"journal_article","status":"public","date_updated":"2023-08-08T13:59:51Z","department":[{"_id":"PeJo"}]},{"article_number":"2912","project":[{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Z00312","name":"The Wittgenstein Prize"}],"citation":{"ista":"Vandael DH, Okamoto Y, Jonas PM. 2021. Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses. Nature Communications. 12(1), 2912.","chicago":"Vandael, David H, Yuji Okamoto, and Peter M Jonas. “Transsynaptic Modulation of Presynaptic Short-Term Plasticity in Hippocampal Mossy Fiber Synapses.” Nature Communications. Springer, 2021. https://doi.org/10.1038/s41467-021-23153-5.","ieee":"D. H. Vandael, Y. Okamoto, and P. M. Jonas, “Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses,” Nature Communications, vol. 12, no. 1. Springer, 2021.","short":"D.H. Vandael, Y. Okamoto, P.M. Jonas, Nature Communications 12 (2021).","ama":"Vandael DH, Okamoto Y, Jonas PM. Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses. Nature Communications. 2021;12(1). doi:10.1038/s41467-021-23153-5","apa":"Vandael, D. H., Okamoto, Y., & Jonas, P. M. (2021). Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses. Nature Communications. Springer. https://doi.org/10.1038/s41467-021-23153-5","mla":"Vandael, David H., et al. “Transsynaptic Modulation of Presynaptic Short-Term Plasticity in Hippocampal Mossy Fiber Synapses.” Nature Communications, vol. 12, no. 1, 2912, Springer, 2021, doi:10.1038/s41467-021-23153-5."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","external_id":{"isi":["000655481800014"]},"article_processing_charge":"No","author":[{"orcid":"0000-0001-7577-1676","full_name":"Vandael, David H","last_name":"Vandael","first_name":"David H","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87"},{"id":"3337E116-F248-11E8-B48F-1D18A9856A87","first_name":"Yuji","full_name":"Okamoto, Yuji","orcid":"0000-0003-0408-6094","last_name":"Okamoto"},{"first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M"}],"title":"Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses","acknowledgement":"We thank Drs. Carolina Borges-Merjane and Jose Guzman for critically reading the manuscript, and Pablo Castillo for discussions. We are grateful to Alois Schlögl for help with analysis, Florian Marr for excellent technical assistance and cell reconstruction, Christina Altmutter for technical help, Eleftheria Kralli-Beller for manuscript editing, and the Scientific Service Units of IST Austria for support. This project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 692692) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award), both to P.J.","oa":1,"publisher":"Springer","quality_controlled":"1","year":"2021","isi":1,"has_accepted_license":"1","publication":"Nature Communications","day":"18","date_created":"2021-08-06T07:22:55Z","date_published":"2021-05-18T00:00:00Z","doi":"10.1038/s41467-021-23153-5","_id":"9778","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","keyword":["general physics and astronomy","general biochemistry","genetics and molecular biology","general chemistry"],"status":"public","date_updated":"2023-08-10T14:16:16Z","ddc":["570"],"file_date_updated":"2021-12-17T11:34:50Z","department":[{"_id":"PeJo"}],"abstract":[{"text":"The hippocampal mossy fiber synapse is a key synapse of the trisynaptic circuit. Post-tetanic potentiation (PTP) is the most powerful form of plasticity at this synaptic connection. It is widely believed that mossy fiber PTP is an entirely presynaptic phenomenon, implying that PTP induction is input-specific, and requires neither activity of multiple inputs nor stimulation of postsynaptic neurons. To directly test cooperativity and associativity, we made paired recordings between single mossy fiber terminals and postsynaptic CA3 pyramidal neurons in rat brain slices. By stimulating non-overlapping mossy fiber inputs converging onto single CA3 neurons, we confirm that PTP is input-specific and non-cooperative. Unexpectedly, mossy fiber PTP exhibits anti-associative induction properties. EPSCs show only minimal PTP after combined pre- and postsynaptic high-frequency stimulation with intact postsynaptic Ca2+ signaling, but marked PTP in the absence of postsynaptic spiking and after suppression of postsynaptic Ca2+ signaling (10 mM EGTA). PTP is largely recovered by inhibitors of voltage-gated R- and L-type Ca2+ channels, group II mGluRs, and vacuolar-type H+-ATPase, suggesting the involvement of retrograde vesicular glutamate signaling. Transsynaptic regulation of PTP extends the repertoire of synaptic computations, implementing a brake on mossy fiber detonation and a “smart teacher” function of hippocampal mossy fiber synapses.","lang":"eng"}],"acknowledged_ssus":[{"_id":"SSU"}],"oa_version":"Published Version","scopus_import":"1","intvolume":" 12","month":"05","publication_status":"published","publication_identifier":{"issn":["2041-1723"]},"language":[{"iso":"eng"}],"file":[{"relation":"main_file","access_level":"open_access","content_type":"application/pdf","success":1,"checksum":"6036a8cdae95e1707c2a04d54e325ff4","file_id":"10563","creator":"kschuh","file_size":3108845,"date_updated":"2021-12-17T11:34:50Z","file_name":"2021_NatureCommunications_Vandael.pdf","date_created":"2021-12-17T11:34:50Z"}],"ec_funded":1,"related_material":{"link":[{"url":"https://ist.ac.at/en/news/synaptic-transmission-not-a-one-way-street/","relation":"press_release","description":"News on IST Homepage"}]},"issue":"1","volume":12},{"file_date_updated":"2021-09-08T12:57:06Z","department":[{"_id":"PeJo"}],"ddc":["612"],"date_updated":"2023-08-11T11:07:51Z","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","_id":"9985","volume":12,"issue":"1","language":[{"iso":"eng"}],"file":[{"success":1,"file_id":"9991","checksum":"1bf4f6a561f96bc426d754de9cb57710","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_name":"2021_NatureCommunications_Watson.pdf","date_created":"2021-09-08T12:57:06Z","file_size":18310502,"date_updated":"2021-09-08T12:57:06Z","creator":"cchlebak"}],"publication_status":"published","publication_identifier":{"eissn":["2041-1723"]},"intvolume":" 12","month":"08","scopus_import":"1","pmid":1,"oa_version":"Published Version","abstract":[{"lang":"eng","text":"AMPA receptor (AMPAR) abundance and positioning at excitatory synapses regulates the strength of transmission. Changes in AMPAR localisation can enact synaptic plasticity, allowing long-term information storage, and is therefore tightly controlled. Multiple mechanisms regulating AMPAR synaptic anchoring have been described, but with limited coherence or comparison between reports, our understanding of this process is unclear. Here, combining synaptic recordings from mouse hippocampal slices and super-resolution imaging in dissociated cultures, we compare the contributions of three AMPAR interaction domains controlling transmission at hippocampal CA1 synapses. We show that the AMPAR C-termini play only a modulatory role, whereas the extracellular N-terminal domain (NTD) and PDZ interactions of the auxiliary subunit TARP γ8 are both crucial, and each is sufficient to maintain transmission. Our data support a model in which γ8 accumulates AMPARs at the postsynaptic density, where the NTD further tunes their positioning. This interplay between cytosolic (TARP γ8) and synaptic cleft (NTD) interactions provides versatility to regulate synaptic transmission and plasticity."}],"title":"AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions","external_id":{"pmid":["34426577 "],"isi":["000687672000006"]},"article_processing_charge":"Yes","author":[{"last_name":"Watson","full_name":"Watson, Jake","orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake"},{"first_name":"Alexandra","last_name":"Pinggera","full_name":"Pinggera, Alexandra"},{"first_name":"Hinze","full_name":"Ho, Hinze","last_name":"Ho"},{"first_name":"Ingo H.","last_name":"Greger","full_name":"Greger, Ingo H."}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"mla":"Watson, Jake, et al. “AMPA Receptor Anchoring at CA1 Synapses Is Determined by N-Terminal Domain and TARP Γ8 Interactions.” Nature Communications, vol. 12, no. 1, 5083, Nature Publishing Group, 2021, doi:10.1038/s41467-021-25281-4.","short":"J. Watson, A. Pinggera, H. Ho, I.H. Greger, Nature Communications 12 (2021).","ieee":"J. Watson, A. Pinggera, H. Ho, and I. H. Greger, “AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions,” Nature Communications, vol. 12, no. 1. Nature Publishing Group, 2021.","ama":"Watson J, Pinggera A, Ho H, Greger IH. AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions. Nature Communications. 2021;12(1). doi:10.1038/s41467-021-25281-4","apa":"Watson, J., Pinggera, A., Ho, H., & Greger, I. H. (2021). AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/s41467-021-25281-4","chicago":"Watson, Jake, Alexandra Pinggera, Hinze Ho, and Ingo H. Greger. “AMPA Receptor Anchoring at CA1 Synapses Is Determined by N-Terminal Domain and TARP Γ8 Interactions.” Nature Communications. Nature Publishing Group, 2021. https://doi.org/10.1038/s41467-021-25281-4.","ista":"Watson J, Pinggera A, Ho H, Greger IH. 2021. AMPA receptor anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions. Nature Communications. 12(1), 5083."},"article_number":"5083","date_created":"2021-09-05T22:01:23Z","date_published":"2021-08-23T00:00:00Z","doi":"10.1038/s41467-021-25281-4","publication":"Nature Communications","day":"23","year":"2021","isi":1,"has_accepted_license":"1","oa":1,"publisher":"Nature Publishing Group","quality_controlled":"1","acknowledgement":"The authors are very grateful to Andrew Penn for advice and discussions on surface receptor labelling in slice tissue, dissociated culture transfection, and for providing tdTomato and BirAER expression plasmids. This work would not have been possible without support from the Biological Services teams at both the Laboratory of Molecular Biology and Ares facilities. We are also very grateful to Nick Barry and Jerome Boulanger of the LMB Light Microscopy facility for support with confocal and STORM imaging and analysis, Junichi Takagi for providing scFv-Clasp expression constructs, Veronica Chang for assistance with scFv-Clasp protein production, and Nejc Kejzar for assistance with cluster analysis. We would like to thank Teru Nakagawa and Ole Paulsen for critical reading of the manuscript and constructive feedback. This work was supported by grants from the Medical Research Council (MC_U105174197) and BBSRC (BB/N002113/1)."},{"type":"journal_article","article_type":"original","status":"public","_id":"9438","department":[{"_id":"PeJo"}],"file_date_updated":"2021-12-02T23:30:05Z","date_updated":"2023-08-10T22:30:51Z","ddc":["570"],"scopus_import":"1","intvolume":" 16","month":"06","acknowledged_ssus":[{"_id":"M-Shop"}],"abstract":[{"lang":"eng","text":"Rigorous investigation of synaptic transmission requires analysis of unitary synaptic events by simultaneous recording from presynaptic terminals and postsynaptic target neurons. However, this has been achieved at only a limited number of model synapses, including the squid giant synapse and the mammalian calyx of Held. Cortical presynaptic terminals have been largely inaccessible to direct presynaptic recording, due to their small size. Here, we describe a protocol for improved subcellular patch-clamp recording in rat and mouse brain slices, with the synapse in a largely intact environment. Slice preparation takes ~2 h, recording ~3 h and post hoc morphological analysis 2 d. Single presynaptic hippocampal mossy fiber terminals are stimulated minimally invasively in the bouton-attached configuration, in which the cytoplasmic content remains unperturbed, or in the whole-bouton configuration, in which the cytoplasmic composition can be precisely controlled. Paired pre–postsynaptic recordings can be integrated with biocytin labeling and morphological analysis, allowing correlative investigation of synapse structure and function. Paired recordings can be obtained from mossy fiber terminals in slices from both rats and mice, implying applicability to genetically modified synapses. Paired recordings can also be performed together with axon tract stimulation or optogenetic activation, allowing comparison of unitary and compound synaptic events in the same target cell. Finally, paired recordings can be combined with spontaneous event analysis, permitting collection of miniature events generated at a single identified synapse. In conclusion, the subcellular patch-clamp techniques detailed here should facilitate analysis of biophysics, plasticity and circuit function of cortical synapses in the mammalian central nervous system."}],"pmid":1,"oa_version":"Submitted Version","ec_funded":1,"volume":16,"issue":"6","publication_status":"published","publication_identifier":{"eissn":["17502799"],"issn":["17542189"]},"language":[{"iso":"eng"}],"file":[{"access_level":"open_access","relation":"main_file","content_type":"application/pdf","checksum":"7eb580abd8893cdb0b410cf41bc8c263","file_id":"9639","embargo":"2021-12-01","creator":"cziletti","date_updated":"2021-12-02T23:30:05Z","file_size":38574802,"date_created":"2021-07-08T12:27:55Z","file_name":"VandaeletalAuthorVersion2021.pdf"}],"project":[{"name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Z00312","name":"The Wittgenstein Prize"},{"name":"Structural plasticity at mossy fiber-CA3 synapses","grant_number":"V00739","_id":"2696E7FE-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"article_processing_charge":"No","external_id":{"pmid":["33990799"],"isi":["000650528700003"]},"author":[{"last_name":"Vandael","orcid":"0000-0001-7577-1676","full_name":"Vandael, David H","first_name":"David H","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87"},{"id":"3337E116-F248-11E8-B48F-1D18A9856A87","first_name":"Yuji","last_name":"Okamoto","full_name":"Okamoto, Yuji","orcid":"0000-0003-0408-6094"},{"first_name":"Carolina","id":"4305C450-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0005-401X","full_name":"Borges Merjane, Carolina","last_name":"Borges Merjane"},{"last_name":"Vargas Barroso","full_name":"Vargas Barroso, Victor M","id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87","first_name":"Victor M"},{"first_name":"Benjamin","id":"4952F31E-F248-11E8-B48F-1D18A9856A87","last_name":"Suter","orcid":"0000-0002-9885-6936","full_name":"Suter, Benjamin"},{"first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas"}],"title":"Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses","citation":{"chicago":"Vandael, David H, Yuji Okamoto, Carolina Borges Merjane, Victor M Vargas Barroso, Benjamin Suter, and Peter M Jonas. “Subcellular Patch-Clamp Techniques for Single-Bouton Stimulation and Simultaneous Pre- and Postsynaptic Recording at Cortical Synapses.” Nature Protocols. Springer Nature, 2021. https://doi.org/10.1038/s41596-021-00526-0.","ista":"Vandael DH, Okamoto Y, Borges Merjane C, Vargas Barroso VM, Suter B, Jonas PM. 2021. Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses. Nature Protocols. 16(6), 2947–2967.","mla":"Vandael, David H., et al. “Subcellular Patch-Clamp Techniques for Single-Bouton Stimulation and Simultaneous Pre- and Postsynaptic Recording at Cortical Synapses.” Nature Protocols, vol. 16, no. 6, Springer Nature, 2021, pp. 2947–2967, doi:10.1038/s41596-021-00526-0.","ieee":"D. H. Vandael, Y. Okamoto, C. Borges Merjane, V. M. Vargas Barroso, B. Suter, and P. M. Jonas, “Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses,” Nature Protocols, vol. 16, no. 6. Springer Nature, pp. 2947–2967, 2021.","short":"D.H. Vandael, Y. Okamoto, C. Borges Merjane, V.M. Vargas Barroso, B. Suter, P.M. Jonas, Nature Protocols 16 (2021) 2947–2967.","apa":"Vandael, D. H., Okamoto, Y., Borges Merjane, C., Vargas Barroso, V. M., Suter, B., & Jonas, P. M. (2021). Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses. Nature Protocols. Springer Nature. https://doi.org/10.1038/s41596-021-00526-0","ama":"Vandael DH, Okamoto Y, Borges Merjane C, Vargas Barroso VM, Suter B, Jonas PM. Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses. Nature Protocols. 2021;16(6):2947–2967. doi:10.1038/s41596-021-00526-0"},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa":1,"quality_controlled":"1","publisher":"Springer Nature","acknowledgement":"This project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award to P.J., V 739-B27 to C.B.M.). We are grateful to F. Marr and C. Altmutter for excellent technical assistance and cell reconstruction, E. Kralli-Beller for manuscript editing, and the Scientific Service Units of IST Austria, especially T. Asenov and Miba machine shop, for maximally efficient support.","page":"2947–2967","date_created":"2021-05-30T22:01:24Z","date_published":"2021-06-01T00:00:00Z","doi":"10.1038/s41596-021-00526-0","year":"2021","has_accepted_license":"1","isi":1,"publication":"Nature Protocols","day":"01"},{"department":[{"_id":"PeJo"}],"file_date_updated":"2022-06-18T22:30:03Z","date_updated":"2023-08-10T22:30:10Z","ddc":["610"],"type":"journal_article","article_type":"original","status":"public","keyword":["general medicine"],"_id":"10816","related_material":{"link":[{"relation":"press_release","url":"https://ista.ac.at/en/news/spot-the-difference/"}],"record":[{"id":"10110","status":"public","relation":"software"}]},"volume":1,"issue":"12","ec_funded":1,"publication_identifier":{"issn":["2662-8457"]},"publication_status":"published","file":[{"file_size":1699466,"date_updated":"2022-06-18T22:30:03Z","creator":"patrickd","file_name":"Guzmanetal2021.pdf","date_created":"2022-06-02T12:51:07Z","content_type":"application/pdf","relation":"main_file","access_level":"open_access","embargo":"2022-06-17","checksum":"9fec5b667909ef52be96d502e4f8c2ae","file_id":"11430"},{"content_type":"application/pdf","access_level":"open_access","relation":"supplementary_material","checksum":"52a005b13a114e3c3a28fa6bbe8b1a8d","file_id":"11431","embargo":"2022-06-17","date_updated":"2022-06-18T22:30:03Z","file_size":3005651,"creator":"patrickd","title":"Supplementary Material","date_created":"2022-06-02T12:53:47Z","file_name":"Guzmanetal2021Suppl.pdf"}],"language":[{"iso":"eng"}],"scopus_import":"1","main_file_link":[{"url":"https://www.biorxiv.org/content/10.1101/647800","open_access":"1"}],"month":"12","intvolume":" 1","acknowledged_ssus":[{"_id":"SSU"}],"abstract":[{"lang":"eng","text":"Pattern separation is a fundamental brain computation that converts small differences in input patterns into large differences in output patterns. Several synaptic mechanisms of pattern separation have been proposed, including code expansion, inhibition and plasticity; however, which of these mechanisms play a role in the entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation circuit, remains unclear. Here we show that a biologically realistic, full-scale EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive inhibitory interneurons (PV+-INs) in the DG, is an efficient pattern separator. Both external gamma-modulated inhibition and internal lateral inhibition mediated by PV+-INs substantially contributed to pattern separation. Both local connectivity and fast signaling at GC–PV+-IN synapses were important for maximum effectiveness. Similarly, mossy fiber synapses with conditional detonator properties contributed to pattern separation. By contrast, perforant path synapses with Hebbian synaptic plasticity and direct EC–CA3 connection shifted the network towards pattern completion. Our results demonstrate that the specific properties of cells and synapses optimize higher-order computations in biological networks and might be useful to improve the deep learning capabilities of technical networks."}],"oa_version":"Submitted Version","author":[{"first_name":"José","id":"30CC5506-F248-11E8-B48F-1D18A9856A87","last_name":"Guzmán","full_name":"Guzmán, José","orcid":"0000-0003-2209-5242"},{"full_name":"Schlögl, Alois","orcid":"0000-0002-5621-8100","last_name":"Schlögl","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","first_name":"Alois"},{"id":"31FFEE2E-F248-11E8-B48F-1D18A9856A87","first_name":"Claudia ","orcid":"0000-0003-4710-2082","full_name":"Espinoza Martinez, Claudia ","last_name":"Espinoza Martinez"},{"id":"423EC9C2-F248-11E8-B48F-1D18A9856A87","first_name":"Xiaomin","full_name":"Zhang, Xiaomin","last_name":"Zhang"},{"last_name":"Suter","orcid":"0000-0002-9885-6936","full_name":"Suter, Benjamin","first_name":"Benjamin","id":"4952F31E-F248-11E8-B48F-1D18A9856A87"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas"}],"article_processing_charge":"No","title":"How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network","citation":{"ista":"Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. 2021. How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. Nature Computational Science. 1(12), 830–842.","chicago":"Guzmán, José, Alois Schlögl, Claudia Espinoza Martinez, Xiaomin Zhang, Benjamin Suter, and Peter M Jonas. “How Connectivity Rules and Synaptic Properties Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3 Network.” Nature Computational Science. Springer Nature, 2021. https://doi.org/10.1038/s43588-021-00157-1.","ama":"Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. Nature Computational Science. 2021;1(12):830-842. doi:10.1038/s43588-021-00157-1","apa":"Guzmán, J., Schlögl, A., Espinoza Martinez, C., Zhang, X., Suter, B., & Jonas, P. M. (2021). How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. Nature Computational Science. Springer Nature. https://doi.org/10.1038/s43588-021-00157-1","short":"J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, P.M. Jonas, Nature Computational Science 1 (2021) 830–842.","ieee":"J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, and P. M. Jonas, “How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network,” Nature Computational Science, vol. 1, no. 12. Springer Nature, pp. 830–842, 2021.","mla":"Guzmán, José, et al. “How Connectivity Rules and Synaptic Properties Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3 Network.” Nature Computational Science, vol. 1, no. 12, Springer Nature, 2021, pp. 830–42, doi:10.1038/s43588-021-00157-1."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","project":[{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse"},{"grant_number":"Z00312","name":"The Wittgenstein Prize","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425"}],"page":"830-842","doi":"10.1038/s43588-021-00157-1","date_published":"2021-12-16T00:00:00Z","date_created":"2022-03-04T08:32:36Z","has_accepted_license":"1","year":"2021","day":"16","publication":"Nature Computational Science","quality_controlled":"1","publisher":"Springer Nature","oa":1,"acknowledgement":"We thank A. Aertsen, N. Kopell, W. Maass, A. Roth, F. Stella and T. Vogels for critically reading earlier versions of the manuscript. We are grateful to F. Marr and C. Altmutter for excellent technical assistance, E. Kralli-Beller for manuscript editing, and the Scientific Service Units of IST Austria for efficient support. Finally, we thank T. Carnevale, L. Erdös, M. Hines, D. Nykamp and D. Schröder for useful discussions, and R. Friedrich and S. Wiechert for sharing unpublished data. This project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 692692, P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award to P.J. and P 31815 to S.J.G.)."},{"author":[{"first_name":"José","id":"30CC5506-F248-11E8-B48F-1D18A9856A87","last_name":"Guzmán","orcid":"0000-0003-2209-5242","full_name":"Guzmán, José"},{"last_name":"Schlögl","full_name":"Schlögl, Alois","orcid":"0000-0002-5621-8100","first_name":"Alois","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Claudia ","id":"31FFEE2E-F248-11E8-B48F-1D18A9856A87","full_name":"Espinoza Martinez, Claudia ","orcid":"0000-0003-4710-2082","last_name":"Espinoza Martinez"},{"first_name":"Xiaomin","id":"423EC9C2-F248-11E8-B48F-1D18A9856A87","last_name":"Zhang","full_name":"Zhang, Xiaomin"},{"last_name":"Suter","orcid":"0000-0002-9885-6936","full_name":"Suter, Benjamin","first_name":"Benjamin","id":"4952F31E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"department":[{"_id":"PeJo"},{"_id":"ScienComp"}],"file_date_updated":"2021-10-08T08:46:04Z","title":"How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network","citation":{"short":"J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, P.M. Jonas, (2021).","ieee":"J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, and P. M. Jonas, “How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network.” IST Austria, 2021.","ama":"Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. 2021. doi:10.15479/AT:ISTA:10110","apa":"Guzmán, J., Schlögl, A., Espinoza Martinez, C., Zhang, X., Suter, B., & Jonas, P. M. (2021). How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. IST Austria. https://doi.org/10.15479/AT:ISTA:10110","mla":"Guzmán, José, et al. How Connectivity Rules and Synaptic Properties Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3 Network. IST Austria, 2021, doi:10.15479/AT:ISTA:10110.","ista":"Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. 2021. How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network, IST Austria, 10.15479/AT:ISTA:10110.","chicago":"Guzmán, José, Alois Schlögl, Claudia Espinoza Martinez, Xiaomin Zhang, Benjamin Suter, and Peter M Jonas. “How Connectivity Rules and Synaptic Properties Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3 Network.” IST Austria, 2021. https://doi.org/10.15479/AT:ISTA:10110."},"date_updated":"2024-03-27T23:30:11Z","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","ddc":["005"],"type":"software","tmp":{"name":"GNU General Public License 3.0","legal_code_url":"https://www.gnu.org/licenses/gpl-3.0.en.html","short":"GPL 3.0"},"status":"public","_id":"10110","doi":"10.15479/AT:ISTA:10110","related_material":{"link":[{"url":"https://ist.ac.at/en/news/spot-the-difference/","relation":"press_release","description":"News on IST Webpage"}],"record":[{"status":"public","id":"10816","relation":"used_for_analysis_in"}]},"date_published":"2021-12-16T00:00:00Z","license":"https://opensource.org/licenses/GPL-3.0","date_created":"2021-10-08T06:44:22Z","has_accepted_license":"1","year":"2021","file":[{"date_created":"2021-10-08T08:46:04Z","file_name":"patternseparation-main (1).zip","creator":"cchlebak","date_updated":"2021-10-08T08:46:04Z","file_size":332990101,"file_id":"10114","checksum":"f92f8931cad0aa7e411c1715337bf408","success":1,"access_level":"open_access","relation":"main_file","content_type":"application/x-zip-compressed"}],"day":"16","publisher":"IST Austria","oa":1,"month":"12","abstract":[{"text":"Pattern separation is a fundamental brain computation that converts small differences in input patterns into large differences in output patterns. Several synaptic mechanisms of pattern separation have been proposed, including code expansion, inhibition and plasticity; however, which of these mechanisms play a role in the entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation circuit, remains unclear. Here we show that a biologically realistic, full-scale EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive inhibitory interneurons (PV+-INs) in the DG, is an efficient pattern separator. Both external gamma-modulated inhibition and internal lateral inhibition mediated by PV+-INs substantially contributed to pattern separation. Both local connectivity and fast signaling at GC–PV+-IN synapses were important for maximum effectiveness. Similarly, mossy fiber synapses with conditional detonator properties contributed to pattern separation. By contrast, perforant path synapses with Hebbian synaptic plasticity and direct EC–CA3 connection shifted the network towards pattern completion. Our results demonstrate that the specific properties of cells and synapses optimize higher-order computations in biological networks and might be useful to improve the deep learning capabilities of technical networks.","lang":"eng"}]},{"_id":"9437","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)"},"ddc":["570"],"date_updated":"2024-03-27T23:30:30Z","department":[{"_id":"RySh"},{"_id":"PeJo"}],"file_date_updated":"2021-05-31T09:43:09Z","oa_version":"Published Version","abstract":[{"lang":"eng","text":"The synaptic connection from medial habenula (MHb) to interpeduncular nucleus (IPN) is critical for emotion-related behaviors and uniquely expresses R-type Ca2+ channels (Cav2.3) and auxiliary GABAB receptor (GBR) subunits, the K+-channel tetramerization domain-containing proteins (KCTDs). Activation of GBRs facilitates or inhibits transmitter release from MHb terminals depending on the IPN subnucleus, but the role of KCTDs is unknown. We therefore examined the localization and function of Cav2.3, GBRs, and KCTDs in this pathway in mice. We show in heterologous cells that KCTD8 and KCTD12b directly bind to Cav2.3 and that KCTD8 potentiates Cav2.3 currents in the absence of GBRs. In the rostral IPN, KCTD8, KCTD12b, and Cav2.3 co-localize at the presynaptic active zone. Genetic deletion indicated a bidirectional modulation of Cav2.3-mediated release by these KCTDs with a compensatory increase of KCTD8 in the active zone in KCTD12b-deficient mice. The interaction of Cav2.3 with KCTDs therefore scales synaptic strength independent of GBR activation."}],"month":"04","intvolume":" 10","scopus_import":"1","file":[{"file_name":"2021_eLife_Bhandari.pdf","date_created":"2021-05-31T09:43:09Z","creator":"cziletti","file_size":8174719,"date_updated":"2021-05-31T09:43:09Z","success":1,"checksum":"6ebcb79999f889766f7cd79ee134ad28","file_id":"9440","relation":"main_file","access_level":"open_access","content_type":"application/pdf"}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["2050-084X"]},"publication_status":"published","volume":10,"related_material":{"record":[{"id":"9562","status":"public","relation":"dissertation_contains"}],"link":[{"url":"https://doi.org/10.1101/2020.04.16.045112","relation":"earlier_version"}]},"ec_funded":1,"article_number":"e68274","project":[{"grant_number":"694539","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","_id":"25CA28EA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"665385","name":"International IST Doctoral Program"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"chicago":"Bhandari, Pradeep, David H Vandael, Diego Fernández-Fernández, Thorsten Fritzius, David Kleindienst, Hüseyin C Önal, Jacqueline-Claire Montanaro-Punzengruber, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from Medial Habenula Terminals.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/ELIFE.68274.","ista":"Bhandari P, Vandael DH, Fernández-Fernández D, Fritzius T, Kleindienst D, Önal HC, Montanaro-Punzengruber J-C, Gassmann M, Jonas PM, Kulik A, Bettler B, Shigemoto R, Koppensteiner P. 2021. GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. eLife. 10, e68274.","mla":"Bhandari, Pradeep, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from Medial Habenula Terminals.” ELife, vol. 10, e68274, eLife Sciences Publications, 2021, doi:10.7554/ELIFE.68274.","short":"P. Bhandari, D.H. Vandael, D. Fernández-Fernández, T. Fritzius, D. Kleindienst, H.C. Önal, J.-C. Montanaro-Punzengruber, M. Gassmann, P.M. Jonas, A. Kulik, B. Bettler, R. Shigemoto, P. Koppensteiner, ELife 10 (2021).","ieee":"P. Bhandari et al., “GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals,” eLife, vol. 10. eLife Sciences Publications, 2021.","ama":"Bhandari P, Vandael DH, Fernández-Fernández D, et al. GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. eLife. 2021;10. doi:10.7554/ELIFE.68274","apa":"Bhandari, P., Vandael, D. H., Fernández-Fernández, D., Fritzius, T., Kleindienst, D., Önal, H. C., … Koppensteiner, P. (2021). GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. ELife. eLife Sciences Publications. https://doi.org/10.7554/ELIFE.68274"},"title":"GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals","author":[{"orcid":"0000-0003-0863-4481","full_name":"Bhandari, Pradeep","last_name":"Bhandari","id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","first_name":"Pradeep"},{"first_name":"David H","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","full_name":"Vandael, David H","orcid":"0000-0001-7577-1676","last_name":"Vandael"},{"first_name":"Diego","full_name":"Fernández-Fernández, Diego","last_name":"Fernández-Fernández"},{"last_name":"Fritzius","full_name":"Fritzius, Thorsten","first_name":"Thorsten"},{"id":"42E121A4-F248-11E8-B48F-1D18A9856A87","first_name":"David","last_name":"Kleindienst","full_name":"Kleindienst, David"},{"first_name":"Hüseyin C","id":"4659D740-F248-11E8-B48F-1D18A9856A87","last_name":"Önal","full_name":"Önal, Hüseyin C","orcid":"0000-0002-2771-2011"},{"id":"3786AB44-F248-11E8-B48F-1D18A9856A87","first_name":"Jacqueline-Claire","last_name":"Montanaro-Punzengruber","full_name":"Montanaro-Punzengruber, Jacqueline-Claire"},{"first_name":"Martin","last_name":"Gassmann","full_name":"Gassmann, Martin"},{"full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Akos","full_name":"Kulik, Akos","last_name":"Kulik"},{"first_name":"Bernhard","last_name":"Bettler","full_name":"Bettler, Bernhard"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi","full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","last_name":"Shigemoto"},{"orcid":"0000-0002-3509-1948","full_name":"Koppensteiner, Peter","last_name":"Koppensteiner","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","first_name":"Peter"}],"external_id":{"isi":["000651761700001"]},"article_processing_charge":"No","acknowledgement":"We are grateful to Akari Hagiwara and Toshihisa Ohtsuka for CAST antibody, and Masahiko Watanabe for neurexin antibody. We thank David Adams for kindly providing the stable Cav2.3 cell line. Cav2.3 KO mice were kindly provided by Tsutomu Tanabe. This project has received funding from the European Research Council (ERC) and European Commission (EC), under the European Union’s Horizon 2020 research and innovation programme (ERC grant agreement no. 694539 to Ryuichi Shigemoto, no. 692692 to Peter Jonas, and the Marie Skłodowska-Curie grant agreement no. 665385 to Cihan Önal), the Swiss National Science Foundation Grant 31003A-172881 to Bernhard Bettler and Deutsche Forschungsgemeinschaft (For 2143) and BIOSS-2 to Akos Kulik.","quality_controlled":"1","publisher":"eLife Sciences Publications","oa":1,"day":"29","publication":"eLife","isi":1,"has_accepted_license":"1","year":"2021","date_published":"2021-04-29T00:00:00Z","doi":"10.7554/ELIFE.68274","date_created":"2021-05-30T22:01:23Z"},{"author":[{"full_name":"Vandael, David H","orcid":"0000-0001-7577-1676","last_name":"Vandael","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","first_name":"David H"},{"first_name":"Carolina","id":"4305C450-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0005-401X","full_name":"Borges Merjane, Carolina","last_name":"Borges Merjane"},{"id":"423EC9C2-F248-11E8-B48F-1D18A9856A87","first_name":"Xiaomin","last_name":"Zhang","full_name":"Zhang, Xiaomin"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas"}],"article_processing_charge":"No","external_id":{"isi":["000556135600004"],"pmid":["32492366"]},"title":"Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation","citation":{"ista":"Vandael DH, Borges Merjane C, Zhang X, Jonas PM. 2020. Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation. Neuron. 107(3), 509–521.","chicago":"Vandael, David H, Carolina Borges Merjane, Xiaomin Zhang, and Peter M Jonas. “Short-Term Plasticity at Hippocampal Mossy Fiber Synapses Is Induced by Natural Activity Patterns and Associated with Vesicle Pool Engram Formation.” Neuron. Elsevier, 2020. https://doi.org/10.1016/j.neuron.2020.05.013.","ama":"Vandael DH, Borges Merjane C, Zhang X, Jonas PM. Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation. Neuron. 2020;107(3):509-521. doi:10.1016/j.neuron.2020.05.013","apa":"Vandael, D. H., Borges Merjane, C., Zhang, X., & Jonas, P. M. (2020). Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2020.05.013","short":"D.H. Vandael, C. Borges Merjane, X. Zhang, P.M. Jonas, Neuron 107 (2020) 509–521.","ieee":"D. H. Vandael, C. Borges Merjane, X. Zhang, and P. M. Jonas, “Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation,” Neuron, vol. 107, no. 3. Elsevier, pp. 509–521, 2020.","mla":"Vandael, David H., et al. “Short-Term Plasticity at Hippocampal Mossy Fiber Synapses Is Induced by Natural Activity Patterns and Associated with Vesicle Pool Engram Formation.” Neuron, vol. 107, no. 3, Elsevier, 2020, pp. 509–21, doi:10.1016/j.neuron.2020.05.013."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","project":[{"grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"The Wittgenstein Prize","grant_number":"Z00312"},{"call_identifier":"FWF","_id":"2696E7FE-B435-11E9-9278-68D0E5697425","name":"Structural plasticity at mossy fiber-CA3 synapses","grant_number":"V00739"}],"page":"509-521","doi":"10.1016/j.neuron.2020.05.013","date_published":"2020-08-05T00:00:00Z","date_created":"2020-06-22T13:29:05Z","isi":1,"has_accepted_license":"1","year":"2020","day":"05","publication":"Neuron","quality_controlled":"1","publisher":"Elsevier","oa":1,"acknowledgement":"This project received funding from the European Research Council (ERC) under the European Union Horizon 2020 Research and Innovation Program (grant agreement 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung ( Z 312-B27 , Wittgenstein award to P.J. and V 739-B27 to C.B.-M.). We thank Drs. Jozsef Csicsvari, Jose Guzman, Erwin Neher, and Ryuichi Shigemoto for commenting on earlier versions of the manuscript. We are grateful to Walter Kaufmann, Daniel Gütl, and Vanessa Zheden for EM training; Alois Schlögl for programming; Florian Marr for excellent technical assistance and cell reconstruction; Christina Altmutter for technical help; Eleftheria Kralli-Beller for manuscript editing; Taija Makinen for providing the Prox1-CreERT2 mouse line; and the Scientific Service Units of IST Austria for support.","file_date_updated":"2020-11-25T11:23:02Z","department":[{"_id":"PeJo"}],"date_updated":"2023-08-22T07:45:25Z","ddc":["570"],"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"},"status":"public","_id":"8001","issue":"3","related_material":{"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/possible-physical-trace-of-short-term-memory-found/"}]},"volume":107,"ec_funded":1,"publication_identifier":{"issn":["0896-6273"],"eissn":["10974199"]},"publication_status":"published","file":[{"checksum":"4030b2be0c9625d54694a1e9fb00305e","file_id":"8811","success":1,"content_type":"application/pdf","access_level":"open_access","relation":"main_file","date_created":"2020-11-25T11:23:02Z","file_name":"2020_Neuron_Vandael.pdf","date_updated":"2020-11-25T11:23:02Z","file_size":4390833,"creator":"dernst"}],"language":[{"iso":"eng"}],"scopus_import":"1","month":"08","intvolume":" 107","abstract":[{"lang":"eng","text":"Post-tetanic potentiation (PTP) is an attractive candidate mechanism for hippocampus-dependent short-term memory. Although PTP has a uniquely large magnitude at hippocampal mossy fiber-CA3 pyramidal neuron synapses, it is unclear whether it can be induced by natural activity and whether its lifetime is sufficient to support short-term memory. We combined in vivo recordings from granule cells (GCs), in vitro paired recordings from mossy fiber terminals and postsynaptic CA3 neurons, and “flash and freeze” electron microscopy. PTP was induced at single synapses and showed a low induction threshold adapted to sparse GC activity in vivo. PTP was mainly generated by enlargement of the readily releasable pool of synaptic vesicles, allowing multiplicative interaction with other plasticity forms. PTP was associated with an increase in the docked vesicle pool, suggesting formation of structural “pool engrams.” Absence of presynaptic activity extended the lifetime of the potentiation, enabling prolonged information storage in the hippocampal network."}],"acknowledged_ssus":[{"_id":"SSU"}],"pmid":1,"oa_version":"Published Version"},{"citation":{"ista":"Zhang X, Schlögl A, Jonas PM. 2020. Selective routing of spatial information flow from input to output in hippocampal granule cells. Neuron. 107(6), 1212–1225.","chicago":"Zhang, Xiaomin, Alois Schlögl, and Peter M Jonas. “Selective Routing of Spatial Information Flow from Input to Output in Hippocampal Granule Cells.” Neuron. Elsevier, 2020. https://doi.org/10.1016/j.neuron.2020.07.006.","apa":"Zhang, X., Schlögl, A., & Jonas, P. M. (2020). Selective routing of spatial information flow from input to output in hippocampal granule cells. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2020.07.006","ama":"Zhang X, Schlögl A, Jonas PM. Selective routing of spatial information flow from input to output in hippocampal granule cells. Neuron. 2020;107(6):1212-1225. doi:10.1016/j.neuron.2020.07.006","ieee":"X. Zhang, A. Schlögl, and P. M. Jonas, “Selective routing of spatial information flow from input to output in hippocampal granule cells,” Neuron, vol. 107, no. 6. Elsevier, pp. 1212–1225, 2020.","short":"X. Zhang, A. Schlögl, P.M. Jonas, Neuron 107 (2020) 1212–1225.","mla":"Zhang, Xiaomin, et al. “Selective Routing of Spatial Information Flow from Input to Output in Hippocampal Granule Cells.” Neuron, vol. 107, no. 6, Elsevier, 2020, pp. 1212–25, doi:10.1016/j.neuron.2020.07.006."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","external_id":{"pmid":["32763145"],"isi":["000579698700009"]},"author":[{"full_name":"Zhang, Xiaomin","last_name":"Zhang","first_name":"Xiaomin","id":"423EC9C2-F248-11E8-B48F-1D18A9856A87"},{"id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","first_name":"Alois","full_name":"Schlögl, Alois","orcid":"0000-0002-5621-8100","last_name":"Schlögl"},{"orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M"}],"title":"Selective routing of spatial information flow from input to output in hippocampal granule cells","project":[{"grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"grant_number":"Z00312","name":"The Wittgenstein Prize","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"year":"2020","isi":1,"has_accepted_license":"1","publication":"Neuron","day":"23","page":"1212-1225","date_created":"2020-08-14T09:36:05Z","doi":"10.1016/j.neuron.2020.07.006","date_published":"2020-09-23T00:00:00Z","acknowledgement":"This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement 692692, P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award, P.J.). We thank Gyorgy Buzsáki, Jozsef Csicsvari, Juan Ramirez Villegas, and Federico Stella for commenting on earlier versions of this manuscript. We also thank Katie Bittner, Michael Brecht, Albert Lee, Jeffery Magee, and Alejandro Pernía-Andrade for sharing expertise in in vivo patch-clamp recording. We are grateful to Florian Marr for cell labeling, cell reconstruction, and technical assistance; Ben Suter for helpful discussions; Christina Altmutter for technical support; Eleftheria Kralli-Beller for manuscript editing; and Todor Asenov (Machine Shop) for device construction. We also thank the Scientific Service Units (SSUs) of IST Austria (Machine Shop, Scientific Computing, and Preclinical Facility) for efficient support.","oa":1,"quality_controlled":"1","publisher":"Elsevier","date_updated":"2023-08-22T08:30:55Z","ddc":["570"],"department":[{"_id":"PeJo"},{"_id":"ScienComp"}],"file_date_updated":"2020-12-04T09:29:21Z","_id":"8261","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"},"article_type":"original","type":"journal_article","status":"public","publication_status":"published","publication_identifier":{"issn":["0896-6273"]},"language":[{"iso":"eng"}],"file":[{"date_created":"2020-12-04T09:29:21Z","file_name":"2020_Neuron_Zhang.pdf","creator":"dernst","date_updated":"2020-12-04T09:29:21Z","file_size":3011120,"checksum":"44a5960fc083a4cb3488d22224859fdc","file_id":"8920","success":1,"access_level":"open_access","relation":"main_file","content_type":"application/pdf"}],"ec_funded":1,"volume":107,"issue":"6","related_material":{"link":[{"description":"News on IST Website","url":"https://ist.ac.at/en/news/the-bouncer-in-the-brain/","relation":"press_release"}]},"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"ScienComp"},{"_id":"PreCl"}],"abstract":[{"lang":"eng","text":"Dentate gyrus granule cells (GCs) connect the entorhinal cortex to the hippocampal CA3 region, but how they process spatial information remains enigmatic. To examine the role of GCs in spatial coding, we measured excitatory postsynaptic potentials (EPSPs) and action potentials (APs) in head-fixed mice running on a linear belt. Intracellular recording from morphologically identified GCs revealed that most cells were active, but activity level varied over a wide range. Whereas only ∼5% of GCs showed spatially tuned spiking, ∼50% received spatially tuned input. Thus, the GC population broadly encodes spatial information, but only a subset relays this information to the CA3 network. Fourier analysis indicated that GCs received conjunctive place-grid-like synaptic input, suggesting code conversion in single neurons. GC firing was correlated with dendritic complexity and intrinsic excitability, but not extrinsic excitatory input or dendritic cable properties. Thus, functional maturation may control input-output transformation and spatial code conversion."}],"oa_version":"Published Version","pmid":1,"intvolume":" 107","month":"09"},{"file_date_updated":"2020-11-20T08:58:53Z","department":[{"_id":"PeJo"}],"ddc":["570"],"date_updated":"2024-03-27T23:30:07Z","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"},"_id":"7473","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"11196"}],"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/flash-and-freeze-reveals-dynamics-of-nerve-connections/"}]},"volume":105,"ec_funded":1,"file":[{"file_size":9712957,"date_updated":"2020-11-20T08:58:53Z","creator":"dernst","file_name":"2020_Neuron_BorgesMerjane.pdf","date_created":"2020-11-20T08:58:53Z","content_type":"application/pdf","relation":"main_file","access_level":"open_access","success":1,"checksum":"3582664addf26859e86ac5bec3e01416","file_id":"8778"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["0896-6273"]},"publication_status":"published","month":"03","intvolume":" 105","scopus_import":"1","oa_version":"Published Version","pmid":1,"abstract":[{"lang":"eng","text":"How structural and functional properties of synapses relate to each other is a fundamental question in neuroscience. Electrophysiology has elucidated mechanisms of synaptic transmission, and electron microscopy (EM) has provided insight into morphological properties of synapses. Here we describe an enhanced method for functional EM (“flash and freeze”), combining optogenetic stimulation with high-pressure freezing. We demonstrate that the improved method can be applied to intact networks in acute brain slices and organotypic slice cultures from mice. As a proof of concept, we probed vesicle pool changes during synaptic transmission at the hippocampal mossy fiber-CA3 pyramidal neuron synapse. Our findings show overlap of the docked vesicle pool and the functionally defined readily releasable pool and provide evidence of fast endocytosis at this synapse. Functional EM with acute slices and slice cultures has the potential to reveal the structural and functional mechanisms of transmission in intact, genetically perturbed, and disease-affected synapses."}],"title":"Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices","author":[{"orcid":"0000-0003-0005-401X","full_name":"Borges Merjane, Carolina","last_name":"Borges Merjane","id":"4305C450-F248-11E8-B48F-1D18A9856A87","first_name":"Carolina"},{"first_name":"Olena","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","full_name":"Kim, Olena","last_name":"Kim"},{"first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas"}],"article_processing_charge":"No","external_id":{"isi":["000520854700008"],"pmid":["31928842"]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"ista":"Borges Merjane C, Kim O, Jonas PM. 2020. Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices. Neuron. 105, 992–1006.","chicago":"Borges Merjane, Carolina, Olena Kim, and Peter M Jonas. “Functional Electron Microscopy (‘Flash and Freeze’) of Identified Cortical Synapses in Acute Brain Slices.” Neuron. Elsevier, 2020. https://doi.org/10.1016/j.neuron.2019.12.022.","ieee":"C. Borges Merjane, O. Kim, and P. M. Jonas, “Functional electron microscopy (‘Flash and Freeze’) of identified cortical synapses in acute brain slices,” Neuron, vol. 105. Elsevier, pp. 992–1006, 2020.","short":"C. Borges Merjane, O. Kim, P.M. Jonas, Neuron 105 (2020) 992–1006.","ama":"Borges Merjane C, Kim O, Jonas PM. Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices. Neuron. 2020;105:992-1006. doi:10.1016/j.neuron.2019.12.022","apa":"Borges Merjane, C., Kim, O., & Jonas, P. M. (2020). Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2019.12.022","mla":"Borges Merjane, Carolina, et al. “Functional Electron Microscopy (‘Flash and Freeze’) of Identified Cortical Synapses in Acute Brain Slices.” Neuron, vol. 105, Elsevier, 2020, pp. 992–1006, doi:10.1016/j.neuron.2019.12.022."},"project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse"},{"call_identifier":"H2020","_id":"25BAF7B2-B435-11E9-9278-68D0E5697425","name":"Presynaptic calcium channels distribution and impact on coupling at the hippocampal mossy fiber synapse","grant_number":"708497"},{"name":"The Wittgenstein Prize","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"name":"Zellkommunikation in Gesundheit und Krankheit","grant_number":"W01205","call_identifier":"FWF","_id":"25C3DBB6-B435-11E9-9278-68D0E5697425"}],"doi":"10.1016/j.neuron.2019.12.022","date_published":"2020-03-18T00:00:00Z","date_created":"2020-02-10T15:59:45Z","page":"992-1006","day":"18","publication":"Neuron","isi":1,"has_accepted_license":"1","year":"2020","publisher":"Elsevier","quality_controlled":"1","oa":1,"acknowledgement":"This project has received funding from the European Research Council (ERC) and European Commission (EC), under the European Union’s Horizon 2020 research and innovation programme (ERC grant agreement No. 692692 and Marie Sklodowska-Curie 708497) and from Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27 Wittgenstein award and DK W1205-B09). We thank Johann Danzl and Ryuichi Shigemoto for critically reading the manuscript; Walter Kaufmann, Daniel Gutl, and Vanessa Zheden for extensive EM training, advice, and experimental assistance; Benjamin Suter for substantial help with light stimulation, ImageJ plugins for analysis, and manuscript editing; Florian Marr and Christina Altmutter for technical support; Eleftheria Kralli-Beller for manuscript editing; Julia König and Paul Wurzinger (Leica Microsystems) for helpful technical discussions; and Taija Makinen for providing the Prox1-CreERT2 mouse line."},{"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"mla":"Dura-Bernal, Salvador, et al. “NetPyNE, a Tool for Data-Driven Multiscale Modeling of Brain Circuits.” ELife, vol. 8, e44494, eLife Sciences Publications, 2019, doi:10.7554/elife.44494.","apa":"Dura-Bernal, S., Suter, B., Gleeson, P., Cantarelli, M., Quintana, A., Rodriguez, F., … Lytton, W. W. (2019). NetPyNE, a tool for data-driven multiscale modeling of brain circuits. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.44494","ama":"Dura-Bernal S, Suter B, Gleeson P, et al. NetPyNE, a tool for data-driven multiscale modeling of brain circuits. eLife. 2019;8. doi:10.7554/elife.44494","short":"S. Dura-Bernal, B. Suter, P. Gleeson, M. Cantarelli, A. Quintana, F. Rodriguez, D.J. Kedziora, G.L. Chadderdon, C.C. Kerr, S.A. Neymotin, R.A. McDougal, M. Hines, G.M. Shepherd, W.W. Lytton, ELife 8 (2019).","ieee":"S. Dura-Bernal et al., “NetPyNE, a tool for data-driven multiscale modeling of brain circuits,” eLife, vol. 8. eLife Sciences Publications, 2019.","chicago":"Dura-Bernal, Salvador, Benjamin Suter, Padraig Gleeson, Matteo Cantarelli, Adrian Quintana, Facundo Rodriguez, David J Kedziora, et al. “NetPyNE, a Tool for Data-Driven Multiscale Modeling of Brain Circuits.” ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/elife.44494.","ista":"Dura-Bernal S, Suter B, Gleeson P, Cantarelli M, Quintana A, Rodriguez F, Kedziora DJ, Chadderdon GL, Kerr CC, Neymotin SA, McDougal RA, Hines M, Shepherd GM, Lytton WW. 2019. NetPyNE, a tool for data-driven multiscale modeling of brain circuits. eLife. 8, e44494."},"title":"NetPyNE, a tool for data-driven multiscale modeling of brain circuits","author":[{"first_name":"Salvador","full_name":"Dura-Bernal, Salvador","last_name":"Dura-Bernal"},{"id":"4952F31E-F248-11E8-B48F-1D18A9856A87","first_name":"Benjamin","full_name":"Suter, Benjamin","orcid":"0000-0002-9885-6936","last_name":"Suter"},{"last_name":"Gleeson","full_name":"Gleeson, Padraig","first_name":"Padraig"},{"first_name":"Matteo","last_name":"Cantarelli","full_name":"Cantarelli, Matteo"},{"first_name":"Adrian","last_name":"Quintana","full_name":"Quintana, Adrian"},{"first_name":"Facundo","full_name":"Rodriguez, Facundo","last_name":"Rodriguez"},{"first_name":"David J","full_name":"Kedziora, David J","last_name":"Kedziora"},{"full_name":"Chadderdon, George L","last_name":"Chadderdon","first_name":"George L"},{"first_name":"Cliff C","last_name":"Kerr","full_name":"Kerr, Cliff C"},{"full_name":"Neymotin, Samuel A","last_name":"Neymotin","first_name":"Samuel A"},{"full_name":"McDougal, Robert A","last_name":"McDougal","first_name":"Robert A"},{"first_name":"Michael","full_name":"Hines, Michael","last_name":"Hines"},{"first_name":"Gordon MG","last_name":"Shepherd","full_name":"Shepherd, Gordon MG"},{"full_name":"Lytton, William W","last_name":"Lytton","first_name":"William W"}],"article_processing_charge":"No","external_id":{"pmid":["31025934"],"isi":["000468968400001"]},"article_number":"e44494","day":"31","publication":"eLife","has_accepted_license":"1","isi":1,"year":"2019","date_published":"2019-05-31T00:00:00Z","doi":"10.7554/elife.44494","date_created":"2020-01-30T09:08:01Z","quality_controlled":"1","publisher":"eLife Sciences Publications","oa":1,"ddc":["570"],"date_updated":"2023-09-07T14:27:52Z","file_date_updated":"2020-07-14T12:47:57Z","department":[{"_id":"PeJo"}],"_id":"7405","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)"},"file":[{"date_created":"2020-02-04T08:41:47Z","file_name":"2019_eLife_DuraBernal.pdf","date_updated":"2020-07-14T12:47:57Z","file_size":6182359,"creator":"dernst","file_id":"7444","checksum":"7014189c11c10a12feeeae37f054871d","content_type":"application/pdf","access_level":"open_access","relation":"main_file"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2050-084X"]},"publication_status":"published","volume":8,"pmid":1,"oa_version":"Published Version","abstract":[{"lang":"eng","text":"Biophysical modeling of neuronal networks helps to integrate and interpret rapidly growing and disparate experimental datasets at multiple scales. The NetPyNE tool (www.netpyne.org) provides both programmatic and graphical interfaces to develop data-driven multiscale network models in NEURON. NetPyNE clearly separates model parameters from implementation code. Users provide specifications at a high level via a standardized declarative language, for example connectivity rules, to create millions of cell-to-cell connections. NetPyNE then enables users to generate the NEURON network, run efficiently parallelized simulations, optimize and explore network parameters through automated batch runs, and use built-in functions for visualization and analysis – connectivity matrices, voltage traces, spike raster plots, local field potentials, and information theoretic measures. NetPyNE also facilitates model sharing by exporting and importing standardized formats (NeuroML and SONATA). NetPyNE is already being used to teach computational neuroscience students and by modelers to investigate brain regions and phenomena."}],"month":"05","intvolume":" 8","scopus_import":"1"},{"_id":"11222","conference":{"start_date":"2019-09-25","location":"Innsbruck, Austria","end_date":"2019-09-27","name":"ANA: Austrian Neuroscience Association ; APHAR: Austrian Pharmacological Society"},"type":"conference_abstract","keyword":["hippocampus","mossy fibers","readily releasable pool","electron microscopy"],"status":"public","date_updated":"2024-03-27T23:30:07Z","department":[{"_id":"PeJo"}],"oa_version":"Published Version","main_file_link":[{"open_access":"1","url":"https://www.intrinsicactivity.org/2019/7/S1/A3.27/"}],"intvolume":" 7","month":"09","publication_status":"published","publication_identifier":{"issn":["2309-8503"]},"language":[{"iso":"eng"}],"ec_funded":1,"related_material":{"record":[{"status":"public","id":"11196","relation":"dissertation_contains"}]},"issue":"Suppl. 1","volume":7,"article_number":"A3.27","project":[{"name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"_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"},{"name":"Zellkommunikation in Gesundheit und Krankheit","grant_number":"W01205","call_identifier":"FWF","_id":"25C3DBB6-B435-11E9-9278-68D0E5697425"},{"grant_number":"Z00312","name":"The Wittgenstein Prize","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"citation":{"short":"O. Kim, C. Borges Merjane, P.M. Jonas, in:, Intrinsic Activity, Austrian Pharmacological Society, 2019.","ieee":"O. Kim, C. Borges Merjane, and P. M. Jonas, “Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy,” in Intrinsic Activity, Innsbruck, Austria, 2019, vol. 7, no. Suppl. 1.","ama":"Kim O, Borges Merjane C, Jonas PM. Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy. In: Intrinsic Activity. Vol 7. Austrian Pharmacological Society; 2019. doi:10.25006/ia.7.s1-a3.27","apa":"Kim, O., Borges Merjane, C., & Jonas, P. M. (2019). Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy. In Intrinsic Activity (Vol. 7). Innsbruck, Austria: Austrian Pharmacological Society. https://doi.org/10.25006/ia.7.s1-a3.27","mla":"Kim, Olena, et al. “Functional Analysis of the Docked Vesicle Pool in Hippocampal Mossy Fiber Terminals by Electron Microscopy.” Intrinsic Activity, vol. 7, no. Suppl. 1, A3.27, Austrian Pharmacological Society, 2019, doi:10.25006/ia.7.s1-a3.27.","ista":"Kim O, Borges Merjane C, Jonas PM. 2019. Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy. Intrinsic Activity. ANA: Austrian Neuroscience Association ; APHAR: Austrian Pharmacological Society vol. 7, A3.27.","chicago":"Kim, Olena, Carolina Borges Merjane, and Peter M Jonas. “Functional Analysis of the Docked Vesicle Pool in Hippocampal Mossy Fiber Terminals by Electron Microscopy.” In Intrinsic Activity, Vol. 7. Austrian Pharmacological Society, 2019. https://doi.org/10.25006/ia.7.s1-a3.27."},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","article_processing_charge":"No","author":[{"last_name":"Kim","full_name":"Kim, Olena","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","first_name":"Olena"},{"last_name":"Borges Merjane","orcid":"0000-0003-0005-401X","full_name":"Borges Merjane, Carolina","id":"4305C450-F248-11E8-B48F-1D18A9856A87","first_name":"Carolina"},{"first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas"}],"title":"Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy","acknowledgement":"This work was supported by the ERC and EU Horizon 2020 (ERC 692692; MSC-IF 708497) and FWF Z 312-B27 Wittgenstein award; W 1205-B09).","oa":1,"quality_controlled":"1","publisher":"Austrian Pharmacological Society","year":"2019","publication":"Intrinsic Activity","day":"11","date_created":"2022-04-20T15:06:05Z","date_published":"2019-09-11T00:00:00Z","doi":"10.25006/ia.7.s1-a3.27"},{"publisher":"Institute of Science and Technology Austria","oa":1,"day":"30","has_accepted_license":"1","year":"2019","doi":"10.15479/AT:ISTA:6363","date_published":"2019-04-30T00:00:00Z","date_created":"2019-04-30T11:56:10Z","page":"140","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"apa":"Espinoza Martinez, C. (2019). Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6363","ama":"Espinoza Martinez C. Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits. 2019. doi:10.15479/AT:ISTA:6363","ieee":"C. Espinoza Martinez, “Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits,” Institute of Science and Technology Austria, 2019.","short":"C. Espinoza Martinez, Parvalbumin+ Interneurons Enable Efficient Pattern Separation in Hippocampal Microcircuits, Institute of Science and Technology Austria, 2019.","mla":"Espinoza Martinez, Claudia. Parvalbumin+ Interneurons Enable Efficient Pattern Separation in Hippocampal Microcircuits. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6363.","ista":"Espinoza Martinez C. 2019. Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits. Institute of Science and Technology Austria.","chicago":"Espinoza Martinez, Claudia . “Parvalbumin+ Interneurons Enable Efficient Pattern Separation in Hippocampal Microcircuits.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6363."},"title":"Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits","author":[{"first_name":"Claudia ","id":"31FFEE2E-F248-11E8-B48F-1D18A9856A87","full_name":"Espinoza Martinez, Claudia ","orcid":"0000-0003-4710-2082","last_name":"Espinoza Martinez"}],"article_processing_charge":"No","oa_version":"Published Version","abstract":[{"text":"Distinguishing between similar experiences is achieved by the brain in a process called pattern separation. In the hippocampus, pattern separation reduces the interference of memories and increases the storage capacity by decorrelating similar inputs patterns of neuronal activity into non-overlapping output firing patterns. Winners-take-all (WTA) mechanism is a theoretical model for pattern separation in which a \"winner\" cell suppresses the activity of the neighboring neurons through feedback inhibition. However, if the network properties of the dentate gyrus support WTA as a biologically conceivable model remains unknown. Here, we showed that the connectivity rules of PV+interneurons and their synaptic properties are optimizedfor efficient pattern separation. We found using multiple whole-cell in vitrorecordings that PV+interneurons mainly connect to granule cells (GC) through lateral inhibition, a form of feedback inhibition in which a GC inhibits other GCs but not itself through the activation of PV+interneurons. Thus, lateral inhibition between GC–PV+interneurons was ~10 times more abundant than recurrent connections. Furthermore, the GC–PV+interneuron connectivity was more spatially confined but less abundant than PV+interneurons–GC connectivity, leading to an asymmetrical distribution of excitatory and inhibitory connectivity. Our network model of the dentate gyrus with incorporated real connectivity rules efficiently decorrelates neuronal activity patterns using WTA as the primary mechanism. This process relied on lateral inhibition, fast-signaling properties of PV+interneurons and the asymmetrical distribution of excitatory and inhibitory connectivity. Finally, we found that silencing the activity of PV+interneurons in vivoleads to acute deficits in discrimination between similar environments, suggesting that PV+interneuron networks are necessary for behavioral relevant computations. Our results demonstrate that PV+interneurons possess unique connectivity and fast signaling properties that confer to the dentate gyrus network properties that allow the emergence of pattern separation. Thus, our results contribute to the knowledge of how specific forms of network organization underlie sophisticated types of information processing. \r\n","lang":"eng"}],"month":"04","alternative_title":["ISTA Thesis"],"file":[{"file_id":"6389","checksum":"77c6c05cfe8b58c8abcf1b854375d084","embargo":"2020-05-09","access_level":"open_access","relation":"main_file","content_type":"application/pdf","date_created":"2019-05-07T16:00:39Z","file_name":"Espinozathesis_all2.pdf","creator":"cespinoza","date_updated":"2021-02-11T11:17:15Z","file_size":13966891},{"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","embargo_to":"open_access","access_level":"closed","relation":"source_file","file_id":"6390","checksum":"f6aa819f127691a2b0fc21c76eb09746","date_updated":"2020-07-14T12:47:28Z","file_size":11159900,"creator":"cespinoza","date_created":"2019-05-07T16:00:48Z","file_name":"Espinoza_Thesis.docx"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-000-8"]},"degree_awarded":"PhD","publication_status":"published","related_material":{"record":[{"status":"public","id":"21","relation":"part_of_dissertation"}]},"_id":"6363","status":"public","type":"dissertation","ddc":["570"],"supervisor":[{"last_name":"Jonas","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"date_updated":"2023-09-15T12:03:48Z","department":[{"_id":"PeJo"}],"file_date_updated":"2021-02-11T11:17:15Z"},{"project":[{"_id":"25C0F108-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons","grant_number":"268548"},{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692"},{"_id":"25C26B1E-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Mechanisms of transmitter release at GABAergic synapses","grant_number":"P24909-B24"},{"grant_number":"Z00312","name":"The Wittgenstein Prize","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425"}],"citation":{"ista":"Hu H, Roth F, Vandael DH, Jonas PM. 2018. Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons. Neuron. 98(1), 156–165.","chicago":"Hu, Hua, Fabian Roth, David H Vandael, and Peter M Jonas. “Complementary Tuning of Na+ and K+ Channel Gating Underlies Fast and Energy-Efficient Action Potentials in GABAergic Interneuron Axons.” Neuron. Elsevier, 2018. https://doi.org/10.1016/j.neuron.2018.02.024.","short":"H. Hu, F. Roth, D.H. Vandael, P.M. Jonas, Neuron 98 (2018) 156–165.","ieee":"H. Hu, F. Roth, D. H. Vandael, and P. M. Jonas, “Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons,” Neuron, vol. 98, no. 1. Elsevier, pp. 156–165, 2018.","ama":"Hu H, Roth F, Vandael DH, Jonas PM. Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons. Neuron. 2018;98(1):156-165. doi:10.1016/j.neuron.2018.02.024","apa":"Hu, H., Roth, F., Vandael, D. H., & Jonas, P. M. (2018). Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2018.02.024","mla":"Hu, Hua, et al. “Complementary Tuning of Na+ and K+ Channel Gating Underlies Fast and Energy-Efficient Action Potentials in GABAergic Interneuron Axons.” Neuron, vol. 98, no. 1, Elsevier, 2018, pp. 156–65, doi:10.1016/j.neuron.2018.02.024."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","external_id":{"isi":["000429192100016"]},"article_processing_charge":"Yes (in subscription journal)","author":[{"id":"4AC0145C-F248-11E8-B48F-1D18A9856A87","first_name":"Hua","last_name":"Hu","full_name":"Hu, Hua"},{"first_name":"Fabian","full_name":"Roth, Fabian","last_name":"Roth"},{"first_name":"David H","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","last_name":"Vandael","orcid":"0000-0001-7577-1676","full_name":"Vandael, David H"},{"full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"publist_id":"7545","title":"Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons","oa":1,"quality_controlled":"1","publisher":"Elsevier","year":"2018","isi":1,"has_accepted_license":"1","publication":"Neuron","day":"04","page":"156 - 165","date_created":"2018-12-11T11:45:48Z","doi":"10.1016/j.neuron.2018.02.024","date_published":"2018-04-04T00:00:00Z","_id":"320","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","status":"public","date_updated":"2023-09-11T12:45:10Z","ddc":["570"],"file_date_updated":"2020-07-14T12:46:03Z","department":[{"_id":"PeJo"}],"abstract":[{"lang":"eng","text":"Fast-spiking, parvalbumin-expressing GABAergic interneurons (PV+-BCs) express a complex machinery of rapid signaling mechanisms, including specialized voltage-gated ion channels to generate brief action potentials (APs). However, short APs are associated with overlapping Na+ and K+ fluxes and are therefore energetically expensive. How the potentially vicious combination of high AP frequency and inefficient spike generation can be reconciled with limited energy supply is presently unclear. To address this question, we performed direct recordings from the PV+-BC axon, the subcellular structure where active conductances for AP initiation and propagation are located. Surprisingly, the energy required for the AP was, on average, only ∼1.6 times the theoretical minimum. High energy efficiency emerged from the combination of fast inactivation of Na+ channels and delayed activation of Kv3-type K+ channels, which minimized ion flux overlap during APs. Thus, the complementary tuning of axonal Na+ and K+ channel gating optimizes both fast signaling properties and metabolic efficiency. Hu et al. demonstrate that action potentials in parvalbumin-expressing GABAergic interneuron axons are energetically efficient, which is highly unexpected given their brief duration. High energy efficiency emerges from the combination of fast inactivation of voltage-gated Na+ channels and delayed activation of Kv3 channels in the axon. "}],"oa_version":"Published Version","scopus_import":"1","intvolume":" 98","month":"04","publication_status":"published","language":[{"iso":"eng"}],"file":[{"file_name":"2018_Neuron_Hu.pdf","date_created":"2018-12-17T10:37:50Z","file_size":3180444,"date_updated":"2020-07-14T12:46:03Z","creator":"dernst","file_id":"5690","checksum":"76070f3729f9c603e1080d0151aa2b11","content_type":"application/pdf","relation":"main_file","access_level":"open_access"}],"ec_funded":1,"issue":"1","volume":98,"related_material":{"link":[{"description":"News on IST Homepage","url":"https://ist.ac.at/en/news/a-certain-type-of-neurons-is-more-energy-efficient-than-previously-assumed/","relation":"press_release"}]}},{"publisher":"Institute of Science and Technology Austria","oa":1,"page":"110","date_published":"2018-03-01T00:00:00Z","doi":"10.15479/AT:ISTA:th_997","date_created":"2018-12-11T11:45:49Z","has_accepted_license":"1","year":"2018","day":"01","author":[{"full_name":"Chen, Chong","last_name":"Chen","id":"3DFD581A-F248-11E8-B48F-1D18A9856A87","first_name":"Chong"}],"publist_id":"7541","article_processing_charge":"No","title":"Synaptotagmins ensure speed and efficiency of inhibitory neurotransmitter release","citation":{"short":"C. Chen, Synaptotagmins Ensure Speed and Efficiency of Inhibitory Neurotransmitter Release, Institute of Science and Technology Austria, 2018.","ieee":"C. Chen, “Synaptotagmins ensure speed and efficiency of inhibitory neurotransmitter release,” Institute of Science and Technology Austria, 2018.","apa":"Chen, C. (2018). Synaptotagmins ensure speed and efficiency of inhibitory neurotransmitter release. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_997","ama":"Chen C. Synaptotagmins ensure speed and efficiency of inhibitory neurotransmitter release. 2018. doi:10.15479/AT:ISTA:th_997","mla":"Chen, Chong. Synaptotagmins Ensure Speed and Efficiency of Inhibitory Neurotransmitter Release. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_997.","ista":"Chen C. 2018. Synaptotagmins ensure speed and efficiency of inhibitory neurotransmitter release. Institute of Science and Technology Austria.","chicago":"Chen, Chong. “Synaptotagmins Ensure Speed and Efficiency of Inhibitory Neurotransmitter Release.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_997."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","alternative_title":["ISTA Thesis"],"month":"03","abstract":[{"text":"Neuronal networks in the brain consist of two main types of neuron, glutamatergic principal neurons and GABAergic interneurons. Although these interneurons only represent 10–20% of the whole population, they mediate feedback and feedforward inhibition and are involved in the generation of high-frequency network oscillations. A hallmark functional property of GABAergic interneurons, especially of the parvalbumin‑expressing (PV+) subtypes, is the speed of signaling at their output synapse across species and brain regions. Several molecular and subcellular factors may underlie the submillisecond signaling at GABAergic synapses. Such as the selective use of P/Q type Ca2+ channels and the tight coupling between Ca2+ channels and Ca2+ sensors of exocytosis. However, whether the molecular identity of the release sensor contributes to these signaling properties remains unclear. Besides, these interneurons are mainly show depression in response to train of stimuli. How could they keep sufficient release to control the activity of postsynaptic principal neurons during high network activity, is largely elusive. For my Ph.D. work, we firstly examined the Ca2+ sensor of exocytosis at the GABAergic basket cell (BC) to Purkinje cell (PC) synapse in the cerebellum. Immunolabeling suggested that BC terminals selectively expressed synaptotagmin 2 (Syt2), whereas synaptotagmin 1 (Syt1) was enriched in excitatory terminals. Genetic elimination of Syt2 reduced action potential-evoked release to ~10% compared to the wild-type control, identifying Syt2 as the major Ca2+ sensor at BC‑PC synapses. Differential adenovirus-mediated rescue revealed Syt2 triggered release with shorter latency and higher temporal precision, and mediated faster vesicle pool replenishment than Syt1. Furthermore, deletion of Syt2 severely reduced and delayed disynaptic inhibition following parallel fiber stimulation. Thus, the selective use of Syt2 as the release sensor at BC–PC synapse ensures fast feedforward inhibition in cerebellar microcircuits. Additionally, we tested the function of another synaptotagmin member, Syt7, for inhibitory synaptic transmission at the BC–PC synapse. Syt7 is thought to be a Ca2+ sensor that mediates asynchronous transmitter release and facilitation at synapses. However, it is strongly expressed in fast-spiking, PV+ GABAergic interneurons and the output synapses of these neurons produce only minimal asynchronous release and show depression rather than facilitation. How could Syt7, a facilitation sensor, contribute to the depressed inhibitory synaptic transmission needs to be further investigated and understood. Our results indicated that at the BC–PC synapse, Syt7 contributes to asynchronous release, pool replenishment and facilitation. In combination, these three effects ensure efficient transmitter release during high‑frequency activity and guarantee frequency independence of inhibition. Taken together, our results confirmed that Syt2, which has the fastest kinetic properties among all synaptotagmin members, is mainly used by the inhibitory BC‑PC synapse for synaptic transmission, contributing to the speed and temporal precision of transmitter release. Furthermore, we showed that Syt7, another highly expressed synaptotagmin member in the output synapses of cerebellar BCs, is used for ensuring efficient inhibitor synaptic transmission during high activity.","lang":"eng"}],"oa_version":"Published Version","related_material":{"record":[{"status":"public","id":"1117","relation":"part_of_dissertation"},{"status":"public","id":"749","relation":"part_of_dissertation"}]},"publication_identifier":{"issn":["2663-337X"]},"degree_awarded":"PhD","publication_status":"published","file":[{"creator":"system","file_size":8719458,"date_updated":"2020-07-14T12:46:04Z","file_name":"IST-2018-997-v1+1_Thesis_chong_a.pdf","date_created":"2018-12-12T10:13:58Z","relation":"main_file","access_level":"open_access","content_type":"application/pdf","checksum":"8e163ae9e927401b9fa7c1b3e6a3631a","file_id":"5046"},{"checksum":"f7d7260029a5fbb5c982db61328ade52","file_id":"6221","relation":"source_file","access_level":"closed","content_type":"application/octet-stream","file_name":"2018_Thesis_chong_source.pages","date_created":"2019-04-05T09:25:26Z","creator":"dernst","file_size":47841940,"date_updated":"2020-07-14T12:46:04Z"}],"language":[{"iso":"eng"}],"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)"},"status":"public","pubrep_id":"997","_id":"324","department":[{"_id":"PeJo"}],"file_date_updated":"2020-07-14T12:46:04Z","supervisor":[{"full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M"}],"date_updated":"2023-09-27T12:26:03Z","ddc":["571"]}]