[{"type":"journal_article","date_updated":"2025-05-14T09:39:37Z","_id":"12875","publisher":"Elsevier","doi":"10.1016/j.neuron.2023.11.009","article_processing_charge":"Yes (via OA deal)","quality_controlled":"1","ddc":["570"],"page":"230-246.e11","external_id":{"pmid":["38096816"]},"related_material":{"link":[{"description":"News on ISTA Website","url":"https://ista.ac.at/en/news/the-pedigree-of-brain-cells/","relation":"press_release"}]},"year":"2024","date_published":"2024-01-17T00:00:00Z","acknowledgement":"We thank Liqun Luo for his continued support, for providing essential resources for generating Fzd10-CreER mice which were generated in his laboratory, and for comments on the manuscript; W. Zhong for providing Nestin-Cre transgenic mouse line for this study; A. Heger for mouse colony management; R. Beattie and T. Asenov for designing and producing components of acute slice recovery chamber for MADM-CloneSeq experiments; and K. Leopold, J. Rodarte and N. Amberg for initial experiments, technical support and/or assistance. This study was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Imaging & Optics Facility (IOF), Laboratory Support Facility (LSF), Miba Machine Shop, and Pre-clinical Facility (PCF). G.C. received funding from European Commission (IST plus postdoctoral fellowship). This work was supported by ISTA institutional\r\nfunds; the Austrian Science Fund Special Research Programmes (FWF SFB F78 Neuro Stem Modulation) to S.H. ","pmid":1,"project":[{"name":"Molecular Mechanisms of Neural Stem Cell Lineage Progression","grant_number":"F07805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E"}],"status":"public","publication":"Neuron","article_type":"comment","date_created":"2023-04-27T09:41:48Z","volume":112,"oa_version":"Published Version","title":"Multipotent progenitors instruct ontogeny of the superior colliculus","author":[{"orcid":"0000-0001-8457-2572","first_name":"Giselle T","full_name":"Cheung, Giselle T","id":"471195F6-F248-11E8-B48F-1D18A9856A87","last_name":"Cheung"},{"last_name":"Pauler","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7462-0048","first_name":"Florian"},{"orcid":"0000-0002-3509-1948","first_name":"Peter","last_name":"Koppensteiner","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","full_name":"Koppensteiner, Peter"},{"first_name":"Thomas","last_name":"Krausgruber","full_name":"Krausgruber, Thomas"},{"full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","last_name":"Streicher","first_name":"Carmen"},{"full_name":"Schrammel, Martin","id":"f13e7cae-e8bd-11ed-841a-96dedf69f46d","last_name":"Schrammel","first_name":"Martin"},{"last_name":"Özgen","full_name":"Özgen, Natalie Y","id":"e68ece33-f6e0-11ea-865d-ae1031dcc090","first_name":"Natalie Y"},{"first_name":"Alexis","last_name":"Ivec","full_name":"Ivec, Alexis","id":"1d144691-e8be-11ed-9b33-bdd3077fad4c"},{"first_name":"Christoph","full_name":"Bock, Christoph","last_name":"Bock"},{"first_name":"Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto"},{"orcid":"0000-0003-2279-1061","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer"}],"day":"17","scopus_import":"1","publication_identifier":{"eisbn":["1234995621"],"issn":["0896-6273"],"issnl":["1234-5678"]},"publication_status":"published","file_date_updated":"2024-02-06T13:56:15Z","intvolume":"       112","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"abstract":[{"text":"The superior colliculus (SC) in the mammalian midbrain is essential for multisensory integration and is composed of a rich diversity of excitatory and inhibitory neurons and glia. However, the developmental principles directing the generation of SC cell-type diversity are not understood. Here, we pursued systematic cell lineage tracing in silico and in vivo, preserving full spatial information, using genetic mosaic analysis with double markers (MADM)-based clonal analysis with single-cell sequencing (MADM-CloneSeq). The analysis of clonally related cell lineages revealed that radial glial progenitors (RGPs) in SC are exceptionally multipotent. Individual resident RGPs have the capacity to produce all excitatory and inhibitory SC neuron types, even at the stage of terminal division. While individual clonal units show no pre-defined cellular composition, the establishment of appropriate relative proportions of distinct neuronal types occurs in a PTEN-dependent manner. Collectively, our findings provide an inaugural framework at the single-RGP/-cell level of the mammalian SC ontogeny.","lang":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"M-Shop"},{"_id":"LifeSc"},{"_id":"PreCl"}],"has_accepted_license":"1","file":[{"file_id":"14944","date_updated":"2024-02-06T13:56:15Z","creator":"dernst","date_created":"2024-02-06T13:56:15Z","file_size":5942467,"checksum":"32b3788f7085cf44a84108d8faaff3ce","relation":"main_file","access_level":"open_access","content_type":"application/pdf","success":1,"file_name":"2024_Neuron_Cheung.pdf"}],"department":[{"_id":"SiHi"},{"_id":"RySh"}],"month":"01","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","issue":"2","language":[{"iso":"eng"}],"oa":1},{"volume":31,"article_type":"original","date_created":"2020-02-28T10:56:18Z","author":[{"first_name":"Felipe A","last_name":"Fredes Tolorza","full_name":"Fredes Tolorza, Felipe A","id":"384825DA-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Silva Sifuentes","id":"371B3D6E-F248-11E8-B48F-1D18A9856A87","full_name":"Silva Sifuentes, Maria A","first_name":"Maria A"},{"first_name":"Peter","full_name":"Koppensteiner, Peter","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","last_name":"Koppensteiner"},{"first_name":"Kenta","full_name":"Kobayashi, Kenta","last_name":"Kobayashi"},{"orcid":"0000-0002-3937-1330","first_name":"Maximilian A","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","full_name":"Jösch, Maximilian A","last_name":"Jösch"},{"last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi","orcid":"0000-0001-8761-9444"}],"day":"11","oa_version":"Published Version","title":"Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation","publication_status":"published","file_date_updated":"2020-10-19T13:31:28Z","has_accepted_license":"1","abstract":[{"lang":"eng","text":"Novelty facilitates formation of memories. The detection of novelty and storage of contextual memories are both mediated by the hippocampus, yet the mechanisms that link these two functions remain to be defined. Dentate granule cells (GCs) of the dorsal hippocampus fire upon novelty exposure forming engrams of contextual memory. However, their key excitatory inputs from the entorhinal cortex are not responsive to novelty and are insufficient to make dorsal GCs fire reliably. Here we uncover a powerful glutamatergic pathway to dorsal GCs from ventral hippocampal mossy cells (MCs) that relays novelty, and is necessary and sufficient for driving dorsal GCs activation. Furthermore, manipulation of ventral MCs activity bidirectionally regulates novelty-induced contextual memory acquisition. Our results show that ventral MCs activity controls memory formation through an intra-hippocampal interaction mechanism gated by novelty."}],"tmp":{"image":"/images/cc_by_nc_nd.png","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","short":"CC BY-NC-ND (4.0)"},"intvolume":"        31","department":[{"_id":"MaJö"},{"_id":"RySh"}],"file":[{"date_updated":"2020-10-19T13:31:28Z","creator":"dernst","file_size":4915964,"date_created":"2020-10-19T13:31:28Z","file_id":"8678","content_type":"application/pdf","access_level":"open_access","file_name":"2021_CurrentBiology_Fredes.pdf","success":1,"checksum":"b7b9c8bc84a08befce365c675229a7d1","relation":"main_file"}],"month":"01","issue":"1","citation":{"ieee":"F. A. Fredes Tolorza, M. A. Silva Sifuentes, P. Koppensteiner, K. Kobayashi, M. A. Jösch, and R. Shigemoto, “Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation,” <i>Current Biology</i>, vol. 31, no. 1. Elsevier, p. P25–38.E5, 2021.","short":"F.A. Fredes Tolorza, M.A. Silva Sifuentes, P. Koppensteiner, K. Kobayashi, M.A. Jösch, R. Shigemoto, Current Biology 31 (2021) P25–38.E5.","ama":"Fredes Tolorza FA, Silva Sifuentes MA, Koppensteiner P, Kobayashi K, Jösch MA, Shigemoto R. Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation. <i>Current Biology</i>. 2021;31(1):P25-38.E5. doi:<a href=\"https://doi.org/10.1016/j.cub.2020.09.074\">10.1016/j.cub.2020.09.074</a>","apa":"Fredes Tolorza, F. A., Silva Sifuentes, M. A., Koppensteiner, P., Kobayashi, K., Jösch, M. A., &#38; Shigemoto, R. (2021). Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation. <i>Current Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cub.2020.09.074\">https://doi.org/10.1016/j.cub.2020.09.074</a>","mla":"Fredes Tolorza, Felipe A., et al. “Ventro-Dorsal Hippocampal Pathway Gates Novelty-Induced Contextual Memory Formation.” <i>Current Biology</i>, vol. 31, no. 1, Elsevier, 2021, p. P25–38.E5, doi:<a href=\"https://doi.org/10.1016/j.cub.2020.09.074\">10.1016/j.cub.2020.09.074</a>.","chicago":"Fredes Tolorza, Felipe A, Maria A Silva Sifuentes, Peter Koppensteiner, Kenta Kobayashi, Maximilian A Jösch, and Ryuichi Shigemoto. “Ventro-Dorsal Hippocampal Pathway Gates Novelty-Induced Contextual Memory Formation.” <i>Current Biology</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.cub.2020.09.074\">https://doi.org/10.1016/j.cub.2020.09.074</a>.","ista":"Fredes Tolorza FA, Silva Sifuentes MA, Koppensteiner P, Kobayashi K, Jösch MA, Shigemoto R. 2021. Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation. Current Biology. 31(1), P25–38.E5."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa":1,"language":[{"iso":"eng"}],"date_updated":"2023-08-04T10:47:11Z","_id":"7551","type":"journal_article","doi":"10.1016/j.cub.2020.09.074","article_processing_charge":"No","publisher":"Elsevier","quality_controlled":"1","page":"P25-38.E5","ddc":["570"],"year":"2021","isi":1,"external_id":{"isi":["000614361000020"]},"related_material":{"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/remembering-novelty/","description":"News on IST Homepage"}]},"ec_funded":1,"acknowledgement":"We thank Peter Jonas and Peter Somogyi for critically reading the manuscript, Satoshi Kida for helpful discussion, Taijia Makinen for providing the Prox1-creERT2 mouse line, and Hiromu Yawo for the VAMP2-Venus construct. We also thank Vivek Jayaraman, Ph.D.; Rex A. Kerr, Ph.D.; Douglas S. Kim, Ph.D.; Loren L. Looger, Ph.D.; and Karel Svoboda, Ph.D. from the GENIE Project, Janelia Farm Research Campus, Howard Hughes Medical Institute for the viral constructs used for GCaMP6s expression. We also thank Jacqueline Montanaro, Vanessa Zheden, David Kleindienst, and Laura Burnett for technical assistance, as well as Robert Beattie for imaging assistance. This work was supported by a European Research Council Advanced Grant 694539 to R.S.","date_published":"2021-01-11T00:00:00Z","project":[{"_id":"25CA28EA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","grant_number":"694539"}],"status":"public","publication":"Current Biology"},{"quality_controlled":"1","ddc":["570"],"_id":"9437","date_updated":"2024-03-25T23:30:16Z","type":"journal_article","article_processing_charge":"No","doi":"10.7554/ELIFE.68274","publisher":"eLife Sciences Publications","ec_funded":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.","date_published":"2021-04-29T00:00:00Z","publication":"eLife","status":"public","project":[{"_id":"25CA28EA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"694539","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour"},{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692","call_identifier":"H2020"},{"call_identifier":"H2020","grant_number":"665385","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"}],"isi":1,"year":"2021","related_material":{"link":[{"relation":"earlier_version","url":"https://doi.org/10.1101/2020.04.16.045112"}],"record":[{"id":"9562","status":"public","relation":"dissertation_contains"}]},"external_id":{"isi":["000651761700001"]},"file_date_updated":"2021-05-31T09:43:09Z","publication_identifier":{"eissn":["2050-084X"]},"publication_status":"published","has_accepted_license":"1","intvolume":"        10","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"abstract":[{"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.","lang":"eng"}],"volume":10,"date_created":"2021-05-30T22:01:23Z","article_type":"original","day":"29","scopus_import":"1","author":[{"id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","full_name":"Bhandari, Pradeep","last_name":"Bhandari","first_name":"Pradeep","orcid":"0000-0003-0863-4481"},{"first_name":"David H","orcid":"0000-0001-7577-1676","last_name":"Vandael","full_name":"Vandael, David H","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Fernández-Fernández, Diego","last_name":"Fernández-Fernández","first_name":"Diego"},{"first_name":"Thorsten","last_name":"Fritzius","full_name":"Fritzius, Thorsten"},{"first_name":"David","last_name":"Kleindienst","id":"42E121A4-F248-11E8-B48F-1D18A9856A87","full_name":"Kleindienst, David"},{"last_name":"Önal","id":"4659D740-F248-11E8-B48F-1D18A9856A87","full_name":"Önal, Hüseyin C","orcid":"0000-0002-2771-2011","first_name":"Hüseyin C"},{"first_name":"Jacqueline-Claire","last_name":"Montanaro-Punzengruber","full_name":"Montanaro-Punzengruber, Jacqueline-Claire","id":"3786AB44-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Gassmann, Martin","last_name":"Gassmann","first_name":"Martin"},{"orcid":"0000-0001-5001-4804","first_name":"Peter M","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas"},{"full_name":"Kulik, Akos","last_name":"Kulik","first_name":"Akos"},{"first_name":"Bernhard","last_name":"Bettler","full_name":"Bettler, Bernhard"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","first_name":"Ryuichi","orcid":"0000-0001-8761-9444"},{"orcid":"0000-0002-3509-1948","first_name":"Peter","last_name":"Koppensteiner","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","full_name":"Koppensteiner, Peter"}],"title":"GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals","oa_version":"Published Version","citation":{"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>","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.","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>.","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.","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>","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>."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa":1,"language":[{"iso":"eng"}],"department":[{"_id":"RySh"},{"_id":"PeJo"}],"article_number":"e68274","file":[{"file_id":"9440","creator":"cziletti","date_updated":"2021-05-31T09:43:09Z","date_created":"2021-05-31T09:43:09Z","file_size":8174719,"checksum":"6ebcb79999f889766f7cd79ee134ad28","relation":"main_file","access_level":"open_access","content_type":"application/pdf","success":1,"file_name":"2021_eLife_Bhandari.pdf"}],"month":"04"},{"publication_identifier":{"issn":["0270-6474"],"eissn":["1529-2401"]},"publication_status":"published","file_date_updated":"2022-05-31T09:10:15Z","has_accepted_license":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"intvolume":"        41","abstract":[{"text":"Rab-interacting molecule (RIM)-binding protein 2 (BP2) is a multidomain protein of the presynaptic active zone (AZ). By binding to RIM, bassoon (Bsn), and voltage-gated Ca2+ channels (CaV), it is considered to be a central organizer of the topography of CaV and release sites of synaptic vesicles (SVs) at the AZ. Here, we used RIM-BP2 knock-out (KO) mice and their wild-type (WT) littermates of either sex to investigate the role of RIM-BP2 at the endbulb of Held synapse of auditory nerve fibers (ANFs) with bushy cells (BCs) of the cochlear nucleus, a fast relay of the auditory pathway with high release probability. Disruption of RIM-BP2 lowered release probability altering short-term plasticity and reduced evoked EPSCs. Analysis of SV pool dynamics during high-frequency train stimulation indicated a reduction of SVs with high release probability but an overall normal size of the readily releasable SV pool (RRP). The Ca2+-dependent fast component of SV replenishment after RRP depletion was slowed. Ultrastructural analysis by superresolution light and electron microscopy revealed an impaired topography of presynaptic CaV and a reduction of docked and membrane-proximal SVs at the AZ. We conclude that RIM-BP2 organizes the topography of CaV, and promotes SV tethering and docking. This way RIM-BP2 is critical for establishing a high initial release probability as required to reliably signal sound onset information that we found to be degraded in BCs of RIM-BP2-deficient mice in vivo. SIGNIFICANCE STATEMENT: Rab-interacting molecule (RIM)-binding proteins (BPs) are key organizers of the active zone (AZ). Using a multidisciplinary approach to the calyceal endbulb of Held synapse that transmits auditory information at rates of up to hundreds of Hertz with submillisecond precision we demonstrate a requirement for RIM-BP2 for normal auditory signaling. Endbulb synapses lacking RIM-BP2 show a reduced release probability despite normal whole-terminal Ca2+ influx and abundance of the key priming protein Munc13-1, a reduced rate of SV replenishment, as well as an altered topography of voltage-gated (CaV)2.1 Ca2+ channels, and fewer docked and membrane proximal synaptic vesicles (SVs). This hampers transmission of sound onset information likely affecting downstream neural computations such as of sound localization.","lang":"eng"}],"volume":41,"article_type":"original","date_created":"2021-09-27T14:33:13Z","author":[{"first_name":"Tanvi","full_name":"Butola, Tanvi","last_name":"Butola"},{"last_name":"Alvanos","full_name":"Alvanos, Theocharis","first_name":"Theocharis"},{"last_name":"Hintze","full_name":"Hintze, Anika","first_name":"Anika"},{"orcid":"0000-0002-3509-1948","first_name":"Peter","last_name":"Koppensteiner","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","full_name":"Koppensteiner, Peter"},{"last_name":"Kleindienst","id":"42E121A4-F248-11E8-B48F-1D18A9856A87","full_name":"Kleindienst, David","first_name":"David"},{"last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","orcid":"0000-0001-8761-9444"},{"full_name":"Wichmann, Carolin","last_name":"Wichmann","first_name":"Carolin"},{"last_name":"Moser","full_name":"Moser, Tobias","first_name":"Tobias"}],"scopus_import":"1","day":"15","title":"RIM-binding protein 2 organizes Ca<sup>21</sup> channel topography and regulates release probability and vesicle replenishment at a fast central synapse","oa_version":"Published Version","issue":"37","citation":{"apa":"Butola, T., Alvanos, T., Hintze, A., Koppensteiner, P., Kleindienst, D., Shigemoto, R., … Moser, T. (2021). RIM-binding protein 2 organizes Ca<sup>21</sup> channel topography and regulates release probability and vesicle replenishment at a fast central synapse. <i>Journal of Neuroscience</i>. Society for Neuroscience. <a href=\"https://doi.org/10.1523/JNEUROSCI.0586-21.2021\">https://doi.org/10.1523/JNEUROSCI.0586-21.2021</a>","mla":"Butola, Tanvi, et al. “RIM-Binding Protein 2 Organizes Ca<sup>21</sup> Channel Topography and Regulates Release Probability and Vesicle Replenishment at a Fast Central Synapse.” <i>Journal of Neuroscience</i>, vol. 41, no. 37, Society for Neuroscience, 2021, pp. 7742–67, doi:<a href=\"https://doi.org/10.1523/JNEUROSCI.0586-21.2021\">10.1523/JNEUROSCI.0586-21.2021</a>.","ista":"Butola T, Alvanos T, Hintze A, Koppensteiner P, Kleindienst D, Shigemoto R, Wichmann C, Moser T. 2021. RIM-binding protein 2 organizes Ca<sup>21</sup> channel topography and regulates release probability and vesicle replenishment at a fast central synapse. Journal of Neuroscience. 41(37), 7742–7767.","chicago":"Butola, Tanvi, Theocharis Alvanos, Anika Hintze, Peter Koppensteiner, David Kleindienst, Ryuichi Shigemoto, Carolin Wichmann, and Tobias Moser. “RIM-Binding Protein 2 Organizes Ca<sup>21</sup> Channel Topography and Regulates Release Probability and Vesicle Replenishment at a Fast Central Synapse.” <i>Journal of Neuroscience</i>. Society for Neuroscience, 2021. <a href=\"https://doi.org/10.1523/JNEUROSCI.0586-21.2021\">https://doi.org/10.1523/JNEUROSCI.0586-21.2021</a>.","ieee":"T. Butola <i>et al.</i>, “RIM-binding protein 2 organizes Ca<sup>21</sup> channel topography and regulates release probability and vesicle replenishment at a fast central synapse,” <i>Journal of Neuroscience</i>, vol. 41, no. 37. Society for Neuroscience, pp. 7742–7767, 2021.","short":"T. Butola, T. Alvanos, A. Hintze, P. Koppensteiner, D. Kleindienst, R. Shigemoto, C. Wichmann, T. Moser, Journal of Neuroscience 41 (2021) 7742–7767.","ama":"Butola T, Alvanos T, Hintze A, et al. RIM-binding protein 2 organizes Ca<sup>21</sup> channel topography and regulates release probability and vesicle replenishment at a fast central synapse. <i>Journal of Neuroscience</i>. 2021;41(37):7742-7767. doi:<a href=\"https://doi.org/10.1523/JNEUROSCI.0586-21.2021\">10.1523/JNEUROSCI.0586-21.2021</a>"},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa":1,"language":[{"iso":"eng"}],"department":[{"_id":"RySh"}],"file":[{"file_size":11571961,"date_created":"2022-05-31T09:10:15Z","date_updated":"2022-05-31T09:10:15Z","creator":"dernst","file_id":"11423","file_name":"2021_JourNeuroscience_Butola.pdf","success":1,"content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"769ab627c7355a50ccfd445e43a5f351"}],"month":"09","quality_controlled":"1","page":"7742-7767","ddc":["570"],"date_updated":"2023-08-14T06:56:30Z","_id":"10051","type":"journal_article","doi":"10.1523/JNEUROSCI.0586-21.2021","article_processing_charge":"No","publisher":"Society for Neuroscience","pmid":1,"date_published":"2021-09-15T00:00:00Z","acknowledgement":"This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) through the Collaborative Sensory Research Center 1286 [to C.W. (A4) and T.M. (B5)] and under Germany’s Excellence Strategy Grant EXC 2067/1-390729940. We thank S. Gerke, A.J. Goldak, and C. Senger-Freitag for expert technical assistance; G. Hoch for developing image analysis routines; and S. Chepurwar and N. Strenzke for technical support and discussion regarding in vivo experiments. We also thank Dr. Christian Rosenmund, Dr. Katharina Grauel, and Dr. Stephan Sigrist for providing RIM-BP2 KO mice and Dr. Masahiko Watanabe for providing the anti-neurexin-antibody, and Dr. Toshihisa Ohtsuka for the anti-ELKS-antibody. J. Neef for help with the STED imaging and image analysis; E. Neher and S. Rizzoli for discussion and comments on the manuscript; K. Eguchi for help with the statistical analysis; and C. H. Huang and J. Neef for constant support and scientific discussion.","publication":"Journal of Neuroscience","status":"public","year":"2021","isi":1,"external_id":{"pmid":["34353898"],"isi":["000752287700005"]}},{"citation":{"mla":"Erdem, Fatma Asli, et al. “A Comparison of the Transport Kinetics of Glycine Transporter 1 and Glycine Transporter 2.” <i>The Journal of General Physiology</i>, vol. 151, no. 8, Rockefeller University Press, 2019, pp. 1035–50, doi:<a href=\"https://doi.org/10.1085/jgp.201912318\">10.1085/jgp.201912318</a>.","apa":"Erdem, F. A., Ilic, M., Koppensteiner, P., Gołacki, J., Lubec, G., Freissmuth, M., &#38; Sandtner, W. (2019). A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2. <i>The Journal of General Physiology</i>. Rockefeller University Press. <a href=\"https://doi.org/10.1085/jgp.201912318\">https://doi.org/10.1085/jgp.201912318</a>","chicago":"Erdem, Fatma Asli, Marija Ilic, Peter Koppensteiner, Jakub Gołacki, Gert Lubec, Michael Freissmuth, and Walter Sandtner. “A Comparison of the Transport Kinetics of Glycine Transporter 1 and Glycine Transporter 2.” <i>The Journal of General Physiology</i>. Rockefeller University Press, 2019. <a href=\"https://doi.org/10.1085/jgp.201912318\">https://doi.org/10.1085/jgp.201912318</a>.","ista":"Erdem FA, Ilic M, Koppensteiner P, Gołacki J, Lubec G, Freissmuth M, Sandtner W. 2019. A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2. The Journal of General Physiology. 151(8), 1035–1050.","short":"F.A. Erdem, M. Ilic, P. Koppensteiner, J. Gołacki, G. Lubec, M. Freissmuth, W. Sandtner, The Journal of General Physiology 151 (2019) 1035–1050.","ieee":"F. A. Erdem <i>et al.</i>, “A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2,” <i>The Journal of General Physiology</i>, vol. 151, no. 8. Rockefeller University Press, pp. 1035–1050, 2019.","ama":"Erdem FA, Ilic M, Koppensteiner P, et al. A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2. <i>The Journal of General Physiology</i>. 2019;151(8):1035-1050. doi:<a href=\"https://doi.org/10.1085/jgp.201912318\">10.1085/jgp.201912318</a>"},"issue":"8","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa":1,"language":[{"iso":"eng"}],"department":[{"_id":"RySh"}],"file":[{"file_name":"2019_JGP_Erdem.pdf","content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"5706b4ccd74ee3e50bf7ecb2a203df71","file_size":2641297,"date_created":"2020-02-05T07:20:32Z","creator":"dernst","date_updated":"2020-07-14T12:47:57Z","file_id":"7450"}],"month":"07","file_date_updated":"2020-07-14T12:47:57Z","publication_identifier":{"issn":["0022-1295"],"eissn":["1540-7748"]},"publication_status":"published","has_accepted_license":"1","tmp":{"image":"/images/cc_by_nc_sa.png","name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","short":"CC BY-NC-SA (4.0)"},"license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","intvolume":"       151","abstract":[{"lang":"eng","text":"Transporters of the solute carrier 6 (SLC6) family translocate their cognate substrate together with Na+ and Cl−. Detailed kinetic models exist for the transporters of GABA (GAT1/SLC6A1) and the monoamines dopamine (DAT/SLC6A3) and serotonin (SERT/SLC6A4). Here, we posited that the transport cycle of individual SLC6 transporters reflects the physiological requirements they operate under. We tested this hypothesis by analyzing the transport cycle of glycine transporter 1 (GlyT1/SLC6A9) and glycine transporter 2 (GlyT2/SLC6A5). GlyT2 is the only SLC6 family member known to translocate glycine, Na+, and Cl− in a 1:3:1 stoichiometry. We analyzed partial reactions in real time by electrophysiological recordings. Contrary to monoamine transporters, both GlyTs were found to have a high transport capacity driven by rapid return of the empty transporter after release of Cl− on the intracellular side. Rapid cycling of both GlyTs was further supported by highly cooperative binding of cosubstrate ions and substrate such that their forward transport mode was maintained even under conditions of elevated intracellular Na+ or Cl−. The most important differences in the transport cycle of GlyT1 and GlyT2 arose from the kinetics of charge movement and the resulting voltage-dependent rate-limiting reactions: the kinetics of GlyT1 were governed by transition of the substrate-bound transporter from outward- to inward-facing conformations, whereas the kinetics of GlyT2 were governed by Na+ binding (or a related conformational change). Kinetic modeling showed that the kinetics of GlyT1 are ideally suited for supplying the extracellular glycine levels required for NMDA receptor activation."}],"volume":151,"date_created":"2020-01-29T16:06:29Z","article_type":"original","day":"03","scopus_import":"1","author":[{"full_name":"Erdem, Fatma Asli","last_name":"Erdem","first_name":"Fatma Asli"},{"full_name":"Ilic, Marija","last_name":"Ilic","first_name":"Marija"},{"orcid":"0000-0002-3509-1948","first_name":"Peter","last_name":"Koppensteiner","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","full_name":"Koppensteiner, Peter"},{"full_name":"Gołacki, Jakub","last_name":"Gołacki","first_name":"Jakub"},{"first_name":"Gert","full_name":"Lubec, Gert","last_name":"Lubec"},{"first_name":"Michael","last_name":"Freissmuth","full_name":"Freissmuth, Michael"},{"last_name":"Sandtner","full_name":"Sandtner, Walter","first_name":"Walter"}],"oa_version":"Published Version","title":"A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2","pmid":1,"date_published":"2019-07-03T00:00:00Z","status":"public","publication":"The Journal of General Physiology","isi":1,"year":"2019","external_id":{"isi":["000478792500008"],"pmid":["31270129"]},"quality_controlled":"1","page":"1035-1050","ddc":["570"],"_id":"7398","date_updated":"2023-09-07T14:52:23Z","type":"journal_article","article_processing_charge":"No","doi":"10.1085/jgp.201912318","publisher":"Rockefeller University Press"}]