[{"article_number":"109125","title":"MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo","day":"09","file":[{"access_level":"open_access","date_created":"2021-04-19T08:30:22Z","checksum":"2a5800d91b96d08b525e17319dcd5e44","file_id":"9339","date_updated":"2021-04-19T08:30:22Z","creator":"dernst","file_size":6924738,"content_type":"application/pdf","relation":"main_file","file_name":"2021_JourNeuroscienceMeth_Zhang.pdf","success":1}],"author":[{"first_name":"Xiaomin","last_name":"Zhang","full_name":"Zhang, Xiaomin","id":"423EC9C2-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Schlögl","first_name":"Alois","id":"45BF87EE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5621-8100","full_name":"Schlögl, Alois"},{"last_name":"Vandael","first_name":"David H","orcid":"0000-0001-7577-1676","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","full_name":"Vandael, David H"},{"full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","first_name":"Peter M"}],"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"article_type":"original","scopus_import":"1","ec_funded":1,"article_processing_charge":"Yes (via OA deal)","publication":"Journal of Neuroscience Methods","department":[{"_id":"PeJo"},{"_id":"ScienComp"}],"publisher":"Elsevier","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","quality_controlled":"1","doi":"10.1016/j.jneumeth.2021.109125","publication_identifier":{"issn":["0165-0270"],"eissn":["1872-678X"]},"issue":"6","language":[{"iso":"eng"}],"isi":1,"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","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"The Wittgenstein Prize"}],"file_date_updated":"2021-04-19T08:30:22Z","date_created":"2021-04-18T22:01:39Z","volume":357,"month":"03","type":"journal_article","oa_version":"Published Version","date_updated":"2023-08-07T14:36:14Z","abstract":[{"lang":"eng","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."}],"_id":"9329","year":"2021","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.","acknowledged_ssus":[{"_id":"SSU"}],"date_published":"2021-03-09T00:00:00Z","ddc":["570"],"has_accepted_license":"1","publication_status":"published","oa":1,"citation":{"short":"X. Zhang, A. Schlögl, D.H. Vandael, P.M. Jonas, Journal of Neuroscience Methods 357 (2021).","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.” <i>Journal of Neuroscience Methods</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.jneumeth.2021.109125\">https://doi.org/10.1016/j.jneumeth.2021.109125</a>.","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,” <i>Journal of Neuroscience Methods</i>, vol. 357, no. 6. Elsevier, 2021.","apa":"Zhang, X., Schlögl, A., Vandael, D. H., &#38; Jonas, P. M. (2021). MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo. <i>Journal of Neuroscience Methods</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.jneumeth.2021.109125\">https://doi.org/10.1016/j.jneumeth.2021.109125</a>","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.","mla":"Zhang, Xiaomin, et al. “MOD: A Novel Machine-Learning Optimal-Filtering Method for Accurate and Efficient Detection of Subthreshold Synaptic Events in Vivo.” <i>Journal of Neuroscience Methods</i>, vol. 357, no. 6, 109125, Elsevier, 2021, doi:<a href=\"https://doi.org/10.1016/j.jneumeth.2021.109125\">10.1016/j.jneumeth.2021.109125</a>.","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. <i>Journal of Neuroscience Methods</i>. 2021;357(6). doi:<a href=\"https://doi.org/10.1016/j.jneumeth.2021.109125\">10.1016/j.jneumeth.2021.109125</a>"},"intvolume":"       357","external_id":{"isi":["000661088500005"]},"status":"public"},{"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"eLife Sciences Publications","department":[{"_id":"RySh"},{"_id":"PeJo"}],"publication":"eLife","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","scopus_import":"1","ec_funded":1,"article_processing_charge":"No","author":[{"orcid":"0000-0003-0863-4481","id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","full_name":"Bhandari, Pradeep","last_name":"Bhandari","first_name":"Pradeep"},{"orcid":"0000-0001-7577-1676","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","full_name":"Vandael, David H","first_name":"David H","last_name":"Vandael"},{"last_name":"Fernández-Fernández","first_name":"Diego","full_name":"Fernández-Fernández, Diego"},{"full_name":"Fritzius, Thorsten","first_name":"Thorsten","last_name":"Fritzius"},{"full_name":"Kleindienst, David","id":"42E121A4-F248-11E8-B48F-1D18A9856A87","first_name":"David","last_name":"Kleindienst"},{"first_name":"Hüseyin C","last_name":"Önal","full_name":"Önal, Hüseyin C","orcid":"0000-0002-2771-2011","id":"4659D740-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Jacqueline-Claire","last_name":"Montanaro-Punzengruber","id":"3786AB44-F248-11E8-B48F-1D18A9856A87","full_name":"Montanaro-Punzengruber, Jacqueline-Claire"},{"full_name":"Gassmann, Martin","first_name":"Martin","last_name":"Gassmann"},{"last_name":"Jonas","first_name":"Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M"},{"first_name":"Akos","last_name":"Kulik","full_name":"Kulik, Akos"},{"last_name":"Bettler","first_name":"Bernhard","full_name":"Bettler, Bernhard"},{"full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto","first_name":"Ryuichi"},{"full_name":"Koppensteiner, Peter","orcid":"0000-0002-3509-1948","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","last_name":"Koppensteiner","first_name":"Peter"}],"file":[{"file_size":8174719,"content_type":"application/pdf","relation":"main_file","creator":"cziletti","file_name":"2021_eLife_Bhandari.pdf","success":1,"date_created":"2021-05-31T09:43:09Z","access_level":"open_access","file_id":"9440","date_updated":"2021-05-31T09:43:09Z","checksum":"6ebcb79999f889766f7cd79ee134ad28"}],"day":"29","article_number":"e68274","title":"GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals","project":[{"grant_number":"694539","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","call_identifier":"H2020","_id":"25CA28EA-B435-11E9-9278-68D0E5697425"},{"name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"International IST Doctoral Program","grant_number":"665385"}],"isi":1,"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["2050-084X"]},"doi":"10.7554/ELIFE.68274","quality_controlled":"1","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.","year":"2021","_id":"9437","oa_version":"Published Version","month":"04","type":"journal_article","date_updated":"2024-03-25T23:30:16Z","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."}],"volume":10,"file_date_updated":"2021-05-31T09:43:09Z","date_created":"2021-05-30T22:01:23Z","external_id":{"isi":["000651761700001"]},"status":"public","intvolume":"        10","related_material":{"record":[{"status":"public","id":"9562","relation":"dissertation_contains"}],"link":[{"url":"https://doi.org/10.1101/2020.04.16.045112","relation":"earlier_version"}]},"citation":{"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. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/ELIFE.68274\">https://doi.org/10.7554/ELIFE.68274</a>","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.” <i>ELife</i>, vol. 10, e68274, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/ELIFE.68274\">10.7554/ELIFE.68274</a>.","ama":"Bhandari P, Vandael DH, Fernández-Fernández D, et al. GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/ELIFE.68274\">10.7554/ELIFE.68274</a>","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).","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.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/ELIFE.68274\">https://doi.org/10.7554/ELIFE.68274</a>.","ieee":"P. Bhandari <i>et al.</i>, “GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021."},"oa":1,"publication_status":"published","has_accepted_license":"1","ddc":["570"],"date_published":"2021-04-29T00:00:00Z"},{"article_type":"original","article_processing_charge":"No","ec_funded":1,"scopus_import":"1","publication":"Nature Protocols","department":[{"_id":"PeJo"}],"pmid":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"Springer Nature","title":"Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses","day":"01","file":[{"file_id":"9639","date_updated":"2021-12-02T23:30:05Z","checksum":"7eb580abd8893cdb0b410cf41bc8c263","date_created":"2021-07-08T12:27:55Z","access_level":"open_access","file_name":"VandaeletalAuthorVersion2021.pdf","file_size":38574802,"content_type":"application/pdf","embargo":"2021-12-01","relation":"main_file","creator":"cziletti"}],"author":[{"first_name":"David H","last_name":"Vandael","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7577-1676","full_name":"Vandael, David H"},{"first_name":"Yuji","last_name":"Okamoto","full_name":"Okamoto, Yuji","id":"3337E116-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0408-6094"},{"first_name":"Carolina","last_name":"Borges Merjane","full_name":"Borges Merjane, Carolina","orcid":"0000-0003-0005-401X","id":"4305C450-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Vargas Barroso","first_name":"Victor M","full_name":"Vargas Barroso, Victor M","id":"2F55A9DE-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Suter, Benjamin","orcid":"0000-0002-9885-6936","id":"4952F31E-F248-11E8-B48F-1D18A9856A87","first_name":"Benjamin","last_name":"Suter"},{"last_name":"Jonas","first_name":"Peter M","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804"}],"issue":"6","language":[{"iso":"eng"}],"isi":1,"project":[{"grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glumatergic synapse"},{"call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize","grant_number":"Z00312"},{"name":"Structural plasticity at mossy fiber-CA3 synapses","_id":"2696E7FE-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"V00739"}],"quality_controlled":"1","doi":"10.1038/s41596-021-00526-0","publication_identifier":{"issn":["17542189"],"eissn":["17502799"]},"_id":"9438","year":"2021","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.","file_date_updated":"2021-12-02T23:30:05Z","date_created":"2021-05-30T22:01:24Z","volume":16,"month":"06","oa_version":"Submitted Version","type":"journal_article","abstract":[{"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.","lang":"eng"}],"date_updated":"2023-08-10T22:30:51Z","page":"2947–2967","citation":{"short":"D.H. Vandael, Y. Okamoto, C. Borges Merjane, V.M. Vargas Barroso, B. Suter, P.M. Jonas, Nature Protocols 16 (2021) 2947–2967.","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,” <i>Nature Protocols</i>, vol. 16, no. 6. Springer Nature, pp. 2947–2967, 2021.","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.” <i>Nature Protocols</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41596-021-00526-0\">https://doi.org/10.1038/s41596-021-00526-0</a>.","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.” <i>Nature Protocols</i>, vol. 16, no. 6, Springer Nature, 2021, pp. 2947–2967, doi:<a href=\"https://doi.org/10.1038/s41596-021-00526-0\">10.1038/s41596-021-00526-0</a>.","apa":"Vandael, D. H., Okamoto, Y., Borges Merjane, C., Vargas Barroso, V. M., Suter, B., &#38; Jonas, P. M. (2021). Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses. <i>Nature Protocols</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41596-021-00526-0\">https://doi.org/10.1038/s41596-021-00526-0</a>","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. <i>Nature Protocols</i>. 2021;16(6):2947–2967. doi:<a href=\"https://doi.org/10.1038/s41596-021-00526-0\">10.1038/s41596-021-00526-0</a>"},"intvolume":"        16","status":"public","external_id":{"isi":["000650528700003"],"pmid":["33990799"]},"acknowledged_ssus":[{"_id":"M-Shop"}],"ddc":["570"],"date_published":"2021-06-01T00:00:00Z","has_accepted_license":"1","publication_status":"published","oa":1},{"department":[{"_id":"PeJo"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"Springer","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_processing_charge":"No","scopus_import":"1","ec_funded":1,"publication":"Nature Communications","day":"18","file":[{"file_size":3108845,"relation":"main_file","content_type":"application/pdf","creator":"kschuh","file_name":"2021_NatureCommunications_Vandael.pdf","success":1,"date_created":"2021-12-17T11:34:50Z","access_level":"open_access","file_id":"10563","date_updated":"2021-12-17T11:34:50Z","checksum":"6036a8cdae95e1707c2a04d54e325ff4"}],"author":[{"id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7577-1676","full_name":"Vandael, David H","first_name":"David H","last_name":"Vandael"},{"last_name":"Okamoto","first_name":"Yuji","full_name":"Okamoto, Yuji","id":"3337E116-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0408-6094"},{"full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","last_name":"Jonas"}],"article_number":"2912","title":"Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses","project":[{"grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"name":"The Wittgenstein Prize","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312"}],"issue":"1","language":[{"iso":"eng"}],"keyword":["general physics and astronomy","general biochemistry","genetics and molecular biology","general chemistry"],"isi":1,"publication_identifier":{"issn":["2041-1723"]},"quality_controlled":"1","doi":"10.1038/s41467-021-23153-5","year":"2021","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.","_id":"9778","type":"journal_article","oa_version":"Published Version","month":"05","date_updated":"2023-08-10T14:16:16Z","abstract":[{"lang":"eng","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."}],"file_date_updated":"2021-12-17T11:34:50Z","date_created":"2021-08-06T07:22:55Z","volume":12,"status":"public","external_id":{"isi":["000655481800014"]},"citation":{"short":"D.H. Vandael, Y. Okamoto, P.M. Jonas, Nature Communications 12 (2021).","ieee":"D. H. Vandael, Y. Okamoto, and P. M. Jonas, “Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses,” <i>Nature Communications</i>, vol. 12, no. 1. Springer, 2021.","chicago":"Vandael, David H, Yuji Okamoto, and Peter M Jonas. “Transsynaptic Modulation of Presynaptic Short-Term Plasticity in Hippocampal Mossy Fiber Synapses.” <i>Nature Communications</i>. Springer, 2021. <a href=\"https://doi.org/10.1038/s41467-021-23153-5\">https://doi.org/10.1038/s41467-021-23153-5</a>.","mla":"Vandael, David H., et al. “Transsynaptic Modulation of Presynaptic Short-Term Plasticity in Hippocampal Mossy Fiber Synapses.” <i>Nature Communications</i>, vol. 12, no. 1, 2912, Springer, 2021, doi:<a href=\"https://doi.org/10.1038/s41467-021-23153-5\">10.1038/s41467-021-23153-5</a>.","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.","apa":"Vandael, D. H., Okamoto, Y., &#38; Jonas, P. M. (2021). Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses. <i>Nature Communications</i>. Springer. <a href=\"https://doi.org/10.1038/s41467-021-23153-5\">https://doi.org/10.1038/s41467-021-23153-5</a>","ama":"Vandael DH, Okamoto Y, Jonas PM. Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses. <i>Nature Communications</i>. 2021;12(1). doi:<a href=\"https://doi.org/10.1038/s41467-021-23153-5\">10.1038/s41467-021-23153-5</a>"},"intvolume":"        12","related_material":{"link":[{"url":"https://ist.ac.at/en/news/synaptic-transmission-not-a-one-way-street/","description":"News on IST Homepage","relation":"press_release"}]},"has_accepted_license":"1","publication_status":"published","oa":1,"acknowledged_ssus":[{"_id":"SSU"}],"ddc":["570"],"date_published":"2021-05-18T00:00:00Z"},{"publication_status":"published","oa":1,"has_accepted_license":"1","date_published":"2020-08-05T00:00:00Z","ddc":["570"],"acknowledged_ssus":[{"_id":"SSU"}],"status":"public","external_id":{"pmid":["32492366"],"isi":["000556135600004"]},"related_material":{"link":[{"relation":"press_release","description":"News on IST Homepage","url":"https://ist.ac.at/en/news/possible-physical-trace-of-short-term-memory-found/"}]},"intvolume":"       107","citation":{"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. <i>Neuron</i>. 2020;107(3):509-521. doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.05.013\">10.1016/j.neuron.2020.05.013</a>","apa":"Vandael, D. H., Borges Merjane, C., Zhang, X., &#38; 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. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2020.05.013\">https://doi.org/10.1016/j.neuron.2020.05.013</a>","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.” <i>Neuron</i>, vol. 107, no. 3, Elsevier, 2020, pp. 509–21, doi:<a href=\"https://doi.org/10.1016/j.neuron.2020.05.013\">10.1016/j.neuron.2020.05.013</a>.","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.” <i>Neuron</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.neuron.2020.05.013\">https://doi.org/10.1016/j.neuron.2020.05.013</a>.","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,” <i>Neuron</i>, vol. 107, no. 3. Elsevier, pp. 509–521, 2020.","short":"D.H. Vandael, C. Borges Merjane, X. Zhang, P.M. Jonas, Neuron 107 (2020) 509–521."},"page":"509-521","type":"journal_article","month":"08","oa_version":"Published Version","date_updated":"2023-08-22T07:45:25Z","abstract":[{"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.","lang":"eng"}],"volume":107,"file_date_updated":"2020-11-25T11:23:02Z","date_created":"2020-06-22T13:29:05Z","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.","year":"2020","_id":"8001","publication_identifier":{"eissn":["10974199"],"issn":["0896-6273"]},"doi":"10.1016/j.neuron.2020.05.013","quality_controlled":"1","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","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"name":"Structural plasticity at mossy fiber-CA3 synapses","_id":"2696E7FE-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"V00739"}],"isi":1,"issue":"3","language":[{"iso":"eng"}],"author":[{"first_name":"David H","last_name":"Vandael","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7577-1676","full_name":"Vandael, David H"},{"last_name":"Borges Merjane","first_name":"Carolina","orcid":"0000-0003-0005-401X","id":"4305C450-F248-11E8-B48F-1D18A9856A87","full_name":"Borges Merjane, Carolina"},{"full_name":"Zhang, Xiaomin","id":"423EC9C2-F248-11E8-B48F-1D18A9856A87","last_name":"Zhang","first_name":"Xiaomin"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas","first_name":"Peter M"}],"day":"05","file":[{"date_created":"2020-11-25T11:23:02Z","access_level":"open_access","date_updated":"2020-11-25T11:23:02Z","file_id":"8811","checksum":"4030b2be0c9625d54694a1e9fb00305e","content_type":"application/pdf","relation":"main_file","file_size":4390833,"creator":"dernst","success":1,"file_name":"2020_Neuron_Vandael.pdf"}],"title":"Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"Elsevier","department":[{"_id":"PeJo"}],"pmid":1,"publication":"Neuron","article_type":"original","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"ec_funded":1,"article_processing_charge":"No","scopus_import":"1"},{"quality_controlled":"1","doi":"10.1016/j.neuron.2018.02.024","project":[{"call_identifier":"FP7","_id":"25C0F108-B435-11E9-9278-68D0E5697425","name":"Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons","grant_number":"268548"},{"name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","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"}],"issue":"1","language":[{"iso":"eng"}],"isi":1,"file":[{"relation":"main_file","content_type":"application/pdf","file_size":3180444,"creator":"dernst","file_name":"2018_Neuron_Hu.pdf","date_created":"2018-12-17T10:37:50Z","access_level":"open_access","date_updated":"2020-07-14T12:46:03Z","file_id":"5690","checksum":"76070f3729f9c603e1080d0151aa2b11"}],"day":"04","author":[{"last_name":"Hu","first_name":"Hua","full_name":"Hu, Hua","id":"4AC0145C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Roth","first_name":"Fabian","full_name":"Roth, Fabian"},{"last_name":"Vandael","first_name":"David H","full_name":"Vandael, David H","orcid":"0000-0001-7577-1676","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Peter M","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M"}],"publist_id":"7545","title":"Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons","department":[{"_id":"PeJo"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publisher":"Elsevier","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_processing_charge":"Yes (in subscription journal)","ec_funded":1,"scopus_import":"1","publication":"Neuron","has_accepted_license":"1","oa":1,"publication_status":"published","ddc":["570"],"date_published":"2018-04-04T00:00:00Z","status":"public","external_id":{"isi":["000429192100016"]},"citation":{"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. <i>Neuron</i>. 2018;98(1):156-165. doi:<a href=\"https://doi.org/10.1016/j.neuron.2018.02.024\">10.1016/j.neuron.2018.02.024</a>","apa":"Hu, H., Roth, F., Vandael, D. H., &#38; Jonas, P. M. (2018). Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2018.02.024\">https://doi.org/10.1016/j.neuron.2018.02.024</a>","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.","mla":"Hu, Hua, et al. “Complementary Tuning of Na+ and K+ Channel Gating Underlies Fast and Energy-Efficient Action Potentials in GABAergic Interneuron Axons.” <i>Neuron</i>, vol. 98, no. 1, Elsevier, 2018, pp. 156–65, doi:<a href=\"https://doi.org/10.1016/j.neuron.2018.02.024\">10.1016/j.neuron.2018.02.024</a>.","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.” <i>Neuron</i>. Elsevier, 2018. <a href=\"https://doi.org/10.1016/j.neuron.2018.02.024\">https://doi.org/10.1016/j.neuron.2018.02.024</a>.","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,” <i>Neuron</i>, vol. 98, no. 1. Elsevier, pp. 156–165, 2018.","short":"H. Hu, F. Roth, D.H. Vandael, P.M. Jonas, Neuron 98 (2018) 156–165."},"related_material":{"link":[{"url":"https://ist.ac.at/en/news/a-certain-type-of-neurons-is-more-energy-efficient-than-previously-assumed/","description":"News on IST Homepage","relation":"press_release"}]},"intvolume":"        98","month":"04","type":"journal_article","oa_version":"Published Version","date_updated":"2023-09-11T12:45:10Z","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. "}],"page":"156 - 165","date_created":"2018-12-11T11:45:48Z","file_date_updated":"2020-07-14T12:46:03Z","volume":98,"year":"2018","_id":"320"},{"article_processing_charge":"No","publication":"Journal of Physiology","_id":"1062","year":"2017","publisher":"Wiley-Blackwell","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","date_created":"2018-12-11T11:49:56Z","publist_id":"6326","volume":595,"title":"Low pH inf o boosts burst firing and catecholamine release by blocking TASK-1 and BK channels while preserving Cav1 channels in mouse chromaffin cells","date_updated":"2023-09-20T12:09:47Z","abstract":[{"text":"Mouse chromaffin cells (MCCs) generate action potential (AP) firing that regulates the Ca2+‐dependent release of catecholamines (CAs). Recent findings indicate that MCCs possess a variety of spontaneous firing modes that span from the common ‘tonic‐irregular’ to the less frequent ‘burst’ firing. This latter is evident in a small fraction of MCCs but occurs regularly when Nav1.3/1.7 channels are made less available or when the Slo1β2‐subunit responsible for BK channel inactivation is deleted. Burst firing causes large increases of Ca2+‐entry and potentiates CA release by ∼3.5‐fold and thus may be a key mechanism for regulating MCC function. With the aim to uncover a physiological role for burst‐firing we investigated the effects of acidosis on MCC activity. Lowering the extracellular pH (pHo) from 7.4 to 7.0 and 6.6 induces cell depolarizations of 10–15 mV that generate repeated bursts. Bursts at pHo 6.6 lasted ∼330 ms, occurred at 1–2 Hz and caused an ∼7‐fold increase of CA cumulative release. Burst firing originates from the inhibition of the pH‐sensitive TASK‐1/TASK‐3 channels and from a 40% BK channel conductance reduction at pHo 7.0. The same pHo had little or no effect on Nav, Cav, Kv and SK channels that support AP firing in MCCs. Burst firing of pHo 6.6 could be mimicked by mixtures of the TASK‐1 blocker A1899 (300 nm) and BK blocker paxilline (300 nm) and could be prevented by blocking L‐type channels by adding 3 μm nifedipine. Mixtures of the two blockers raised cumulative CA‐secretion even more than low pHo (∼12‐fold), showing that the action of protons on vesicle release is mainly a result of the ionic conductance changes that increase Ca2+‐entry during bursts. Our data provide direct evidence suggesting that MCCs respond to low pHo with sustained depolarization, burst firing and enhanced CA‐secretion, thus mimicking the physiological response of CCs to acute acidosis and hyperkalaemia generated during heavy exercise and muscle fatigue.","lang":"eng"}],"day":"15","type":"journal_article","month":"04","oa_version":"None","page":"2587 - 2609 ","author":[{"full_name":"Guarina, Laura","first_name":"Laura","last_name":"Guarina"},{"first_name":"David H","last_name":"Vandael","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7577-1676","full_name":"Vandael, David H"},{"first_name":"Valentina","last_name":"Carabelli","full_name":"Carabelli, Valentina"},{"full_name":"Carbone, Emilio","last_name":"Carbone","first_name":"Emilio"}],"language":[{"iso":"eng"}],"citation":{"chicago":"Guarina, Laura, David H Vandael, Valentina Carabelli, and Emilio Carbone. “Low PH Inf o Boosts Burst Firing and Catecholamine Release by Blocking TASK-1 and BK Channels While Preserving Cav1 Channels in Mouse Chromaffin Cells.” <i>Journal of Physiology</i>. Wiley-Blackwell, 2017. <a href=\"https://doi.org/10.1113/JP273735\">https://doi.org/10.1113/JP273735</a>.","ieee":"L. Guarina, D. H. Vandael, V. Carabelli, and E. Carbone, “Low pH inf o boosts burst firing and catecholamine release by blocking TASK-1 and BK channels while preserving Cav1 channels in mouse chromaffin cells,” <i>Journal of Physiology</i>, vol. 595, no. 8. Wiley-Blackwell, pp. 2587–2609, 2017.","short":"L. Guarina, D.H. Vandael, V. Carabelli, E. Carbone, Journal of Physiology 595 (2017) 2587–2609.","ama":"Guarina L, Vandael DH, Carabelli V, Carbone E. Low pH inf o boosts burst firing and catecholamine release by blocking TASK-1 and BK channels while preserving Cav1 channels in mouse chromaffin cells. <i>Journal of Physiology</i>. 2017;595(8):2587-2609. doi:<a href=\"https://doi.org/10.1113/JP273735\">10.1113/JP273735</a>","apa":"Guarina, L., Vandael, D. H., Carabelli, V., &#38; Carbone, E. (2017). Low pH inf o boosts burst firing and catecholamine release by blocking TASK-1 and BK channels while preserving Cav1 channels in mouse chromaffin cells. <i>Journal of Physiology</i>. Wiley-Blackwell. <a href=\"https://doi.org/10.1113/JP273735\">https://doi.org/10.1113/JP273735</a>","ista":"Guarina L, Vandael DH, Carabelli V, Carbone E. 2017. Low pH inf o boosts burst firing and catecholamine release by blocking TASK-1 and BK channels while preserving Cav1 channels in mouse chromaffin cells. Journal of Physiology. 595(8), 2587–2609.","mla":"Guarina, Laura, et al. “Low PH Inf o Boosts Burst Firing and Catecholamine Release by Blocking TASK-1 and BK Channels While Preserving Cav1 Channels in Mouse Chromaffin Cells.” <i>Journal of Physiology</i>, vol. 595, no. 8, Wiley-Blackwell, 2017, pp. 2587–609, doi:<a href=\"https://doi.org/10.1113/JP273735\">10.1113/JP273735</a>."},"issue":"8","intvolume":"       595","isi":1,"extern":"1","status":"public","external_id":{"isi":["000399430300022"]},"quality_controlled":"1","doi":"10.1113/JP273735","date_published":"2017-04-15T00:00:00Z","publication_status":"published"},{"date_created":"2018-12-11T11:54:19Z","file_date_updated":"2020-07-14T12:45:19Z","volume":85,"month":"03","type":"journal_article","oa_version":"Published Version","abstract":[{"lang":"eng","text":"Based on extrapolation from excitatory synapses, it is often assumed that depletion of the releasable pool of synaptic vesicles is the main factor underlying depression at inhibitory synapses. In this issue of Neuron, using subcellular patch-clamp recording from inhibitory presynaptic terminals, Kawaguchi and Sakaba (2015) show that at Purkinje cell-deep cerebellar nuclei neuron synapses, changes in presynaptic action potential waveform substantially contribute to synaptic depression. Based on extrapolation from excitatory synapses, it is often assumed that depletion of the releasable pool of synaptic vesicles is the main factor underlying depression at inhibitory synapses. In this issue of Neuron, using subcellular patch-clamp recording from inhibitory presynaptic terminals, Kawaguchi and Sakaba (2015) show that at Purkinje cell-deep cerebellar nuclei neuron synapses, changes in presynaptic action potential waveform substantially contribute to synaptic depression."}],"date_updated":"2021-10-08T09:07:34Z","page":"1149 - 1151","_id":"1845","year":"2015","ddc":["570"],"date_published":"2015-03-18T00:00:00Z","has_accepted_license":"1","oa":1,"publication_status":"published","citation":{"ieee":"D. H. Vandael, C. Espinoza Martinez, and P. M. Jonas, “Excitement about inhibitory presynaptic terminals,” <i>Neuron</i>, vol. 85, no. 6. Elsevier, pp. 1149–1151, 2015.","chicago":"Vandael, David H, Claudia  Espinoza Martinez, and Peter M Jonas. “Excitement about Inhibitory Presynaptic Terminals.” <i>Neuron</i>. Elsevier, 2015. <a href=\"https://doi.org/10.1016/j.neuron.2015.03.006\">https://doi.org/10.1016/j.neuron.2015.03.006</a>.","short":"D.H. Vandael, C. Espinoza Martinez, P.M. Jonas, Neuron 85 (2015) 1149–1151.","ama":"Vandael DH, Espinoza Martinez C, Jonas PM. Excitement about inhibitory presynaptic terminals. <i>Neuron</i>. 2015;85(6):1149-1151. doi:<a href=\"https://doi.org/10.1016/j.neuron.2015.03.006\">10.1016/j.neuron.2015.03.006</a>","ista":"Vandael DH, Espinoza Martinez C, Jonas PM. 2015. Excitement about inhibitory presynaptic terminals. Neuron. 85(6), 1149–1151.","mla":"Vandael, David H., et al. “Excitement about Inhibitory Presynaptic Terminals.” <i>Neuron</i>, vol. 85, no. 6, Elsevier, 2015, pp. 1149–51, doi:<a href=\"https://doi.org/10.1016/j.neuron.2015.03.006\">10.1016/j.neuron.2015.03.006</a>.","apa":"Vandael, D. H., Espinoza Martinez, C., &#38; Jonas, P. M. (2015). Excitement about inhibitory presynaptic terminals. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2015.03.006\">https://doi.org/10.1016/j.neuron.2015.03.006</a>"},"intvolume":"        85","status":"public","publist_id":"5256","title":"Excitement about inhibitory presynaptic terminals","license":"https://creativecommons.org/licenses/by-nc/4.0/","day":"18","file":[{"file_name":"IST-2017-822-v1+1_Perspective_Fig__Final.pdf","file_size":411832,"relation":"main_file","content_type":"application/pdf","creator":"system","file_id":"5192","date_updated":"2020-07-14T12:45:19Z","checksum":"d1808550e376a0eca2a950fda017cfa6","date_created":"2018-12-12T10:16:07Z","access_level":"open_access"},{"file_name":"IST-2017-822-v1+2_Perspective_Final2.pdf","creator":"system","file_size":100769,"relation":"main_file","content_type":"application/pdf","checksum":"a279f4ae61e6c8f33d68f69a0d02097d","file_id":"5193","date_updated":"2020-07-14T12:45:19Z","access_level":"open_access","date_created":"2018-12-12T10:16:07Z"}],"author":[{"id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7577-1676","full_name":"Vandael, David H","last_name":"Vandael","first_name":"David H"},{"first_name":"Claudia ","last_name":"Espinoza Martinez","id":"31FFEE2E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4710-2082","full_name":"Espinoza Martinez, Claudia "},{"full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","last_name":"Jonas"}],"tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","short":"CC BY-NC (4.0)","image":"/images/cc_by_nc.png","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode"},"scopus_import":"1","article_processing_charge":"No","publication":"Neuron","department":[{"_id":"PeJo"}],"publisher":"Elsevier","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","quality_controlled":"1","doi":"10.1016/j.neuron.2015.03.006","pubrep_id":"822","issue":"6","language":[{"iso":"eng"}]},{"page":"149 - 161","month":"10","type":"journal_article","oa_version":"Submitted Version","date_updated":"2021-01-12T06:51:26Z","abstract":[{"lang":"eng","text":"Neuronal and neuroendocrine L-type calcium channels (Cav1.2, Cav1.3) open readily at relatively low membrane potentials and allow Ca2+ to enter the cells near resting potentials. In this way, Cav1.2 and Cav1.3 shape the action potential waveform, contribute to gene expression, synaptic plasticity, neuronal differentiation, hormone secretion and pacemaker activity. In the chromaffin cells (CCs) of the adrenal medulla, Cav1.3 is highly expressed and is shown to support most of the pacemaking current that sustains action potential (AP) firings and part of the catecholamine secretion. Cav1.3 forms Ca2+-nanodomains with the fast inactivating BK channels and drives the resting SK currents. These latter set the inter-spike interval duration between consecutive spikes during spontaneous firing and the rate of spike adaptation during sustained depolarizations. Cav1.3 plays also a primary role in the switch from “tonic” to “burst” firing that occurs in mouse CCs when either the availability of voltage-gated Na channels (Nav) is reduced or the β2 subunit featuring the fast inactivating BK channels is deleted. Here, we discuss the functional role of these “neuronlike” firing modes in CCs and how Cav1.3 contributes to them. The open issue is to understand how these novel firing patterns are adapted to regulate the quantity of circulating catecholamines during resting condition or in response to acute and chronic stress."}],"volume":8,"date_created":"2018-12-11T11:52:35Z","acknowledgement":"This work was supported by the Italian MIUR (PRIN 2010/2011 project 2010JFYFY2) and the University of Torino.","year":"2015","_id":"1535","publication_status":"published","oa":1,"date_published":"2015-10-01T00:00:00Z","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384372/","open_access":"1"}],"external_id":{"pmid":["25966692"]},"status":"public","intvolume":"         8","citation":{"mla":"Vandael, David H., et al. “Cav1.3 Channels as Key Regulators of Neuron-like Firings and Catecholamine Release in Chromaffin Cells.” <i>Current Molecular Pharmacology</i>, vol. 8, no. 2, Bentham Science Publishers, 2015, pp. 149–61, doi:<a href=\"https://doi.org/10.2174/1874467208666150507105443\">10.2174/1874467208666150507105443</a>.","ista":"Vandael DH, Marcantoni A, Carbone E. 2015. Cav1.3 channels as key regulators of neuron-like firings and catecholamine release in chromaffin cells. Current Molecular Pharmacology. 8(2), 149–161.","apa":"Vandael, D. H., Marcantoni, A., &#38; Carbone, E. (2015). Cav1.3 channels as key regulators of neuron-like firings and catecholamine release in chromaffin cells. <i>Current Molecular Pharmacology</i>. Bentham Science Publishers. <a href=\"https://doi.org/10.2174/1874467208666150507105443\">https://doi.org/10.2174/1874467208666150507105443</a>","ama":"Vandael DH, Marcantoni A, Carbone E. Cav1.3 channels as key regulators of neuron-like firings and catecholamine release in chromaffin cells. <i>Current Molecular Pharmacology</i>. 2015;8(2):149-161. doi:<a href=\"https://doi.org/10.2174/1874467208666150507105443\">10.2174/1874467208666150507105443</a>","short":"D.H. Vandael, A. Marcantoni, E. Carbone, Current Molecular Pharmacology 8 (2015) 149–161.","ieee":"D. H. Vandael, A. Marcantoni, and E. Carbone, “Cav1.3 channels as key regulators of neuron-like firings and catecholamine release in chromaffin cells,” <i>Current Molecular Pharmacology</i>, vol. 8, no. 2. Bentham Science Publishers, pp. 149–161, 2015.","chicago":"Vandael, David H, Andrea Marcantoni, and Emilio Carbone. “Cav1.3 Channels as Key Regulators of Neuron-like Firings and Catecholamine Release in Chromaffin Cells.” <i>Current Molecular Pharmacology</i>. Bentham Science Publishers, 2015. <a href=\"https://doi.org/10.2174/1874467208666150507105443\">https://doi.org/10.2174/1874467208666150507105443</a>."},"author":[{"last_name":"Vandael","first_name":"David H","full_name":"Vandael, David H","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7577-1676"},{"last_name":"Marcantoni","first_name":"Andrea","full_name":"Marcantoni, Andrea"},{"full_name":"Carbone, Emilio","first_name":"Emilio","last_name":"Carbone"}],"day":"01","title":"Cav1.3 channels as key regulators of neuron-like firings and catecholamine release in chromaffin cells","publist_id":"5636","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Bentham Science Publishers","department":[{"_id":"PeJo"}],"pmid":1,"publication":"Current Molecular Pharmacology","article_type":"original","article_processing_charge":"No","scopus_import":1,"doi":"10.2174/1874467208666150507105443","quality_controlled":"1","issue":"2","language":[{"iso":"eng"}]},{"doi":"10.1113/JP271078","quality_controlled":"1","language":[{"iso":"eng"}],"issue":"22","title":"Dual action of leptin on rest-firing and stimulated catecholamine release via phosphoinositide 3-kinase-riven BK channel up-regulation in mouse chromaffin cells","publist_id":"5606","author":[{"last_name":"Gavello","first_name":"Daniela","full_name":"Gavello, Daniela"},{"full_name":"Vandael, David H","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7577-1676","first_name":"David H","last_name":"Vandael"},{"first_name":"Sara","last_name":"Gosso","full_name":"Gosso, Sara"},{"last_name":"Carbone","first_name":"Emilio","full_name":"Carbone, Emilio"},{"full_name":"Carabelli, Valentina","last_name":"Carabelli","first_name":"Valentina"}],"day":"15","publication":"Journal of Physiology","scopus_import":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Wiley-Blackwell","pmid":1,"department":[{"_id":"PeJo"}],"date_published":"2015-11-15T00:00:00Z","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650409/","open_access":"1"}],"publication_status":"published","oa":1,"intvolume":"       593","citation":{"ieee":"D. Gavello, D. H. Vandael, S. Gosso, E. Carbone, and V. Carabelli, “Dual action of leptin on rest-firing and stimulated catecholamine release via phosphoinositide 3-kinase-riven BK channel up-regulation in mouse chromaffin cells,” <i>Journal of Physiology</i>, vol. 593, no. 22. Wiley-Blackwell, pp. 4835–4853, 2015.","chicago":"Gavello, Daniela, David H Vandael, Sara Gosso, Emilio Carbone, and Valentina Carabelli. “Dual Action of Leptin on Rest-Firing and Stimulated Catecholamine Release via Phosphoinositide 3-Kinase-Riven BK Channel up-Regulation in Mouse Chromaffin Cells.” <i>Journal of Physiology</i>. Wiley-Blackwell, 2015. <a href=\"https://doi.org/10.1113/JP271078\">https://doi.org/10.1113/JP271078</a>.","short":"D. Gavello, D.H. Vandael, S. Gosso, E. Carbone, V. Carabelli, Journal of Physiology 593 (2015) 4835–4853.","ama":"Gavello D, Vandael DH, Gosso S, Carbone E, Carabelli V. Dual action of leptin on rest-firing and stimulated catecholamine release via phosphoinositide 3-kinase-riven BK channel up-regulation in mouse chromaffin cells. <i>Journal of Physiology</i>. 2015;593(22):4835-4853. doi:<a href=\"https://doi.org/10.1113/JP271078\">10.1113/JP271078</a>","mla":"Gavello, Daniela, et al. “Dual Action of Leptin on Rest-Firing and Stimulated Catecholamine Release via Phosphoinositide 3-Kinase-Riven BK Channel up-Regulation in Mouse Chromaffin Cells.” <i>Journal of Physiology</i>, vol. 593, no. 22, Wiley-Blackwell, 2015, pp. 4835–53, doi:<a href=\"https://doi.org/10.1113/JP271078\">10.1113/JP271078</a>.","ista":"Gavello D, Vandael DH, Gosso S, Carbone E, Carabelli V. 2015. Dual action of leptin on rest-firing and stimulated catecholamine release via phosphoinositide 3-kinase-riven BK channel up-regulation in mouse chromaffin cells. Journal of Physiology. 593(22), 4835–4853.","apa":"Gavello, D., Vandael, D. H., Gosso, S., Carbone, E., &#38; Carabelli, V. (2015). Dual action of leptin on rest-firing and stimulated catecholamine release via phosphoinositide 3-kinase-riven BK channel up-regulation in mouse chromaffin cells. <i>Journal of Physiology</i>. Wiley-Blackwell. <a href=\"https://doi.org/10.1113/JP271078\">https://doi.org/10.1113/JP271078</a>"},"status":"public","external_id":{"pmid":["26282459"]},"volume":593,"date_created":"2018-12-11T11:52:45Z","page":"4835 - 4853","abstract":[{"text":"Leptin is an adipokine produced by the adipose tissue regulating body weight through its appetite-suppressing effect. Besides being expressed in the hypothalamus and hippocampus, leptin receptors (ObRs) are also present in chromaffin cells of the adrenal medulla. In the present study, we report the effect of leptin on mouse chromaffin cell (MCC) functionality, focusing on cell excitability and catecholamine secretion. Acute application of leptin (1 nm) on spontaneously firing MCCs caused a slowly developing membrane hyperpolarization followed by complete blockade of action potential (AP) firing. This inhibitory effect at rest was abolished by the BK channel blocker paxilline (1 μm), suggesting the involvement of BK potassium channels. Single-channel recordings in 'perforated microvesicles' confirmed that leptin increased BK channel open probability without altering its unitary conductance. BK channel up-regulation was associated with the phosphoinositide 3-kinase (PI3K) signalling cascade because the PI3K specific inhibitor wortmannin (100 nm) fully prevented BK current increase. We also tested the effect of leptin on evoked AP firing and Ca2+-driven exocytosis. Although leptin preserves well-adapted AP trains of lower frequency, APs are broader and depolarization-evoked exocytosis is increased as a result of the larger size of the ready-releasable pool and higher frequency of vesicle release. The kinetics and quantal size of single secretory events remained unaltered. Leptin had no effect on firing and secretion in db-/db- mice lacking the ObR gene, confirming its specificity. In conclusion, leptin exhibits a dual action on MCC activity. It dampens AP firing at rest but preserves AP firing and increases catecholamine secretion during sustained stimulation, highlighting the importance of the adipo-adrenal axis in the leptin-mediated increase of sympathetic tone and catecholamine release.","lang":"eng"}],"date_updated":"2021-01-12T06:51:38Z","oa_version":"Submitted Version","type":"journal_article","month":"11","_id":"1565","acknowledgement":"This work was supported by the Compagnia di San Paolo Foundation ‘Neuroscience Program’ to VC and ‘Progetto di Ateneo 2011-13’ to EC.\r\nWe thank Dr Claudio Franchino for cell preparation and for providing excellent technical support.","year":"2015"},{"language":[{"iso":"eng"}],"doi":"10.1016/j.neuroscience.2015.10.046","quality_controlled":"1","publication":"Neuroscience","scopus_import":1,"article_processing_charge":"No","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"article_type":"original","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Elsevier","department":[{"_id":"PeJo"}],"title":"Knock-down of synapsin alters cell excitability and action potential waveform by potentiating BK and voltage gated Ca2 currents in Helix serotonergic neurons","publist_id":"5591","author":[{"full_name":"Brenes, Oscar","first_name":"Oscar","last_name":"Brenes"},{"full_name":"Vandael, David H","orcid":"0000-0001-7577-1676","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","first_name":"David H","last_name":"Vandael"},{"full_name":"Carbone, Emilio","first_name":"Emilio","last_name":"Carbone"},{"full_name":"Montarolo, Pier","first_name":"Pier","last_name":"Montarolo"},{"last_name":"Ghirardi","first_name":"Mirella","full_name":"Ghirardi, Mirella"}],"day":"17","file":[{"file_name":"2015_Neuroscience_Brenes.pdf","file_size":5563015,"relation":"main_file","content_type":"application/pdf","creator":"dernst","file_id":"7849","date_updated":"2020-07-14T12:45:02Z","checksum":"af2c4c994718c7be417eba0dc746aac9","date_created":"2020-05-15T06:50:20Z","access_level":"open_access"}],"intvolume":"       311","citation":{"short":"O. Brenes, D.H. Vandael, E. Carbone, P. Montarolo, M. Ghirardi, Neuroscience 311 (2015) 430–443.","chicago":"Brenes, Oscar, David H Vandael, Emilio Carbone, Pier Montarolo, and Mirella Ghirardi. “Knock-down of Synapsin Alters Cell Excitability and Action Potential Waveform by Potentiating BK and Voltage Gated Ca2 Currents in Helix Serotonergic Neurons.” <i>Neuroscience</i>. Elsevier, 2015. <a href=\"https://doi.org/10.1016/j.neuroscience.2015.10.046\">https://doi.org/10.1016/j.neuroscience.2015.10.046</a>.","ieee":"O. Brenes, D. H. Vandael, E. Carbone, P. Montarolo, and M. Ghirardi, “Knock-down of synapsin alters cell excitability and action potential waveform by potentiating BK and voltage gated Ca2 currents in Helix serotonergic neurons,” <i>Neuroscience</i>, vol. 311. Elsevier, pp. 430–443, 2015.","apa":"Brenes, O., Vandael, D. H., Carbone, E., Montarolo, P., &#38; Ghirardi, M. (2015). Knock-down of synapsin alters cell excitability and action potential waveform by potentiating BK and voltage gated Ca2 currents in Helix serotonergic neurons. <i>Neuroscience</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuroscience.2015.10.046\">https://doi.org/10.1016/j.neuroscience.2015.10.046</a>","ista":"Brenes O, Vandael DH, Carbone E, Montarolo P, Ghirardi M. 2015. Knock-down of synapsin alters cell excitability and action potential waveform by potentiating BK and voltage gated Ca2 currents in Helix serotonergic neurons. Neuroscience. 311, 430–443.","mla":"Brenes, Oscar, et al. “Knock-down of Synapsin Alters Cell Excitability and Action Potential Waveform by Potentiating BK and Voltage Gated Ca2 Currents in Helix Serotonergic Neurons.” <i>Neuroscience</i>, vol. 311, Elsevier, 2015, pp. 430–43, doi:<a href=\"https://doi.org/10.1016/j.neuroscience.2015.10.046\">10.1016/j.neuroscience.2015.10.046</a>.","ama":"Brenes O, Vandael DH, Carbone E, Montarolo P, Ghirardi M. Knock-down of synapsin alters cell excitability and action potential waveform by potentiating BK and voltage gated Ca2 currents in Helix serotonergic neurons. <i>Neuroscience</i>. 2015;311:430-443. doi:<a href=\"https://doi.org/10.1016/j.neuroscience.2015.10.046\">10.1016/j.neuroscience.2015.10.046</a>"},"status":"public","date_published":"2015-12-17T00:00:00Z","ddc":["570"],"publication_status":"published","oa":1,"has_accepted_license":"1","_id":"1580","year":"2015","volume":311,"file_date_updated":"2020-07-14T12:45:02Z","date_created":"2018-12-11T11:52:50Z","page":"430 - 443","date_updated":"2021-01-12T06:51:44Z","abstract":[{"text":"Synapsins (Syns) are an evolutionarily conserved family of presynaptic proteins crucial for the fine-tuning of synaptic function. A large amount of experimental evidences has shown that Syns are involved in the development of epileptic phenotypes and several mutations in Syn genes have been associated with epilepsy in humans and animal models. Syn mutations induce alterations in circuitry and neurotransmitter release, differentially affecting excitatory and inhibitory synapses, thus causing an excitation/inhibition imbalance in network excitability toward hyperexcitability that may be a determinant with regard to the development of epilepsy. Another approach to investigate epileptogenic mechanisms is to understand how silencing Syn affects the cellular behavior of single neurons and is associated with the hyperexcitable phenotypes observed in epilepsy. Here, we examined the functional effects of antisense-RNA inhibition of Syn expression on individually identified and isolated serotonergic cells of the Helix land snail. We found that Helix synapsin silencing increases cell excitability characterized by a slightly depolarized resting membrane potential, decreases the rheobase, reduces the threshold for action potential (AP) firing and increases the mean and instantaneous firing rates, with respect to control cells. The observed increase of Ca2+ and BK currents in Syn-silenced cells seems to be related to changes in the shape of the AP waveform. These currents sustain the faster spiking in Syn-deficient cells by increasing the after hyperpolarization and limiting the Na+ and Ca2+ channel inactivation during repetitive firing. This in turn speeds up the depolarization phase by reaching the AP threshold faster. Our results provide evidence that Syn silencing increases intrinsic cell excitability associated with increased Ca2+ and Ca2+-dependent BK currents in the absence of excitatory or inhibitory inputs.","lang":"eng"}],"oa_version":"Submitted Version","type":"journal_article","month":"12"}]