[{"oa":1,"tmp":{"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)","image":"/images/cc_by_nc_nd.png"},"external_id":{"isi":["000614361000020"]},"isi":1,"quality_controlled":"1","project":[{"_id":"25CA28EA-B435-11E9-9278-68D0E5697425","grant_number":"694539","call_identifier":"H2020","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour"}],"doi":"10.1016/j.cub.2020.09.074","language":[{"iso":"eng"}],"month":"01","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.","year":"2021","publication_status":"published","department":[{"_id":"MaJö"},{"_id":"RySh"}],"publisher":"Elsevier","author":[{"id":"384825DA-F248-11E8-B48F-1D18A9856A87","last_name":"Fredes Tolorza","first_name":"Felipe A","full_name":"Fredes Tolorza, Felipe A"},{"full_name":"Silva Sifuentes, Maria A","id":"371B3D6E-F248-11E8-B48F-1D18A9856A87","last_name":"Silva Sifuentes","first_name":"Maria A"},{"full_name":"Koppensteiner, Peter","first_name":"Peter","last_name":"Koppensteiner","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Kobayashi, Kenta","first_name":"Kenta","last_name":"Kobayashi"},{"id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3937-1330","first_name":"Maximilian A","last_name":"Jösch","full_name":"Jösch, Maximilian A"},{"first_name":"Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi"}],"related_material":{"link":[{"url":"https://ist.ac.at/en/news/remembering-novelty/","description":"News on IST Homepage","relation":"press_release"}]},"date_created":"2020-02-28T10:56:18Z","date_updated":"2023-08-04T10:47:11Z","volume":31,"file_date_updated":"2020-10-19T13:31:28Z","ec_funded":1,"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","publication":"Current Biology","citation":{"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. Current Biology. 2021;31(1):P25-38.E5. doi:10.1016/j.cub.2020.09.074","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,” Current Biology, vol. 31, no. 1. Elsevier, p. P25–38.E5, 2021.","apa":"Fredes Tolorza, F. A., Silva Sifuentes, M. A., Koppensteiner, P., Kobayashi, K., Jösch, M. A., & Shigemoto, R. (2021). Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation. Current Biology. Elsevier. https://doi.org/10.1016/j.cub.2020.09.074","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.","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.","mla":"Fredes Tolorza, Felipe A., et al. “Ventro-Dorsal Hippocampal Pathway Gates Novelty-Induced Contextual Memory Formation.” Current Biology, vol. 31, no. 1, Elsevier, 2021, p. P25–38.E5, doi:10.1016/j.cub.2020.09.074.","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.” Current Biology. Elsevier, 2021. https://doi.org/10.1016/j.cub.2020.09.074."},"article_type":"original","page":"P25-38.E5","date_published":"2021-01-11T00:00:00Z","day":"11","article_processing_charge":"No","has_accepted_license":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"7551","status":"public","ddc":["570"],"title":"Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation","intvolume":" 31","file":[{"file_name":"2021_CurrentBiology_Fredes.pdf","access_level":"open_access","content_type":"application/pdf","file_size":4915964,"creator":"dernst","relation":"main_file","file_id":"8678","date_created":"2020-10-19T13:31:28Z","date_updated":"2020-10-19T13:31:28Z","checksum":"b7b9c8bc84a08befce365c675229a7d1","success":1}],"oa_version":"Published Version","type":"journal_article","abstract":[{"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.","lang":"eng"}],"issue":"1"},{"doi":"10.1073/pnas.1920827118","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"EM-Fac"}],"oa":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","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000637398300002"]},"project":[{"grant_number":"694539","_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"}],"quality_controlled":"1","isi":1,"publication_identifier":{"eissn":["1091-6490"]},"month":"04","author":[{"last_name":"Schöpf","first_name":"Clemens L.","full_name":"Schöpf, Clemens L."},{"full_name":"Ablinger, Cornelia","first_name":"Cornelia","last_name":"Ablinger"},{"first_name":"Stefanie M.","last_name":"Geisler","full_name":"Geisler, Stefanie M."},{"full_name":"Stanika, Ruslan I.","last_name":"Stanika","first_name":"Ruslan I."},{"full_name":"Campiglio, Marta","first_name":"Marta","last_name":"Campiglio"},{"id":"3F99E422-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9735-5315","first_name":"Walter","last_name":"Kaufmann","full_name":"Kaufmann, Walter"},{"full_name":"Nimmervoll, Benedikt","first_name":"Benedikt","last_name":"Nimmervoll"},{"full_name":"Schlick, Bettina","first_name":"Bettina","last_name":"Schlick"},{"full_name":"Brockhaus, Johannes","first_name":"Johannes","last_name":"Brockhaus"},{"first_name":"Markus","last_name":"Missler","full_name":"Missler, Markus"},{"first_name":"Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi"},{"full_name":"Obermair, Gerald J.","last_name":"Obermair","first_name":"Gerald J."}],"volume":118,"date_created":"2021-04-18T22:01:40Z","date_updated":"2023-08-08T13:08:47Z","acknowledgement":"We thank Arnold Schwartz for providing α2δ-1 knockout mice; Ariane Benedetti, Sabine Baumgartner, Sandra Demetz, and Irene Mahlknecht for technical support; Nadine Ortner and Andreas Lieb for electrophysiological experiments; the team of the Electron Microscopy Facility at the Institute of Science and Technology Austria for technical support related to ultrastructural analysis; Hermann Dietrich and Anja Beierfuß and her team for animal care; Jutta Engel and Jörg Striessnig for critical discussions; and Bruno Benedetti and Bernhard Flucher for critical discussions and reading the manuscript. This study was supported by Austrian Science Fund Grants P24079, F44060, F44150, and DOC30-B30 (to G.J.O.) and T855 (to M.C.), European Research Council Grant AdG 694539 (to R.S.), Deutsche Forschungsgemeinschaft\r\nGrant SFB1348-TP A03 (to M.M.), and Interdisziplinäre Zentrum für Klinische Forschung Münster Grant Mi3/004/19 (to M.M.). This work is part of the PhD theses of C.L.S., S.M.G., and C.A.","year":"2021","department":[{"_id":"EM-Fac"},{"_id":"RySh"}],"publisher":"National Academy of Sciences","publication_status":"published","ec_funded":1,"file_date_updated":"2021-04-19T10:10:56Z","license":"https://creativecommons.org/licenses/by/4.0/","date_published":"2021-04-06T00:00:00Z","citation":{"short":"C.L. Schöpf, C. Ablinger, S.M. Geisler, R.I. Stanika, M. Campiglio, W. Kaufmann, B. Nimmervoll, B. Schlick, J. Brockhaus, M. Missler, R. Shigemoto, G.J. Obermair, PNAS 118 (2021).","mla":"Schöpf, Clemens L., et al. “Presynaptic Α2δ Subunits Are Key Organizers of Glutamatergic Synapses.” PNAS, vol. 118, no. 14, National Academy of Sciences, 2021, doi:10.1073/pnas.1920827118.","chicago":"Schöpf, Clemens L., Cornelia Ablinger, Stefanie M. Geisler, Ruslan I. Stanika, Marta Campiglio, Walter Kaufmann, Benedikt Nimmervoll, et al. “Presynaptic Α2δ Subunits Are Key Organizers of Glutamatergic Synapses.” PNAS. National Academy of Sciences, 2021. https://doi.org/10.1073/pnas.1920827118.","ama":"Schöpf CL, Ablinger C, Geisler SM, et al. Presynaptic α2δ subunits are key organizers of glutamatergic synapses. PNAS. 2021;118(14). doi:10.1073/pnas.1920827118","ieee":"C. L. Schöpf et al., “Presynaptic α2δ subunits are key organizers of glutamatergic synapses,” PNAS, vol. 118, no. 14. National Academy of Sciences, 2021.","apa":"Schöpf, C. L., Ablinger, C., Geisler, S. M., Stanika, R. I., Campiglio, M., Kaufmann, W., … Obermair, G. J. (2021). Presynaptic α2δ subunits are key organizers of glutamatergic synapses. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.1920827118","ista":"Schöpf CL, Ablinger C, Geisler SM, Stanika RI, Campiglio M, Kaufmann W, Nimmervoll B, Schlick B, Brockhaus J, Missler M, Shigemoto R, Obermair GJ. 2021. Presynaptic α2δ subunits are key organizers of glutamatergic synapses. PNAS. 118(14)."},"publication":"PNAS","article_type":"original","article_processing_charge":"No","has_accepted_license":"1","day":"06","scopus_import":"1","file":[{"date_created":"2021-04-19T10:10:56Z","date_updated":"2021-04-19T10:10:56Z","success":1,"checksum":"dd014f68ae9d7d8d8fc4139a24e04506","file_id":"9340","relation":"main_file","creator":"dernst","file_size":2603911,"content_type":"application/pdf","file_name":"2021_PNAS_Schoepf.pdf","access_level":"open_access"}],"oa_version":"Published Version","_id":"9330","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":" 118","status":"public","title":"Presynaptic α2δ subunits are key organizers of glutamatergic synapses","ddc":["570"],"issue":"14","abstract":[{"text":"In nerve cells the genes encoding for α2δ subunits of voltage-gated calcium channels have been linked to synaptic functions and neurological disease. Here we show that α2δ subunits are essential for the formation and organization of glutamatergic synapses. Using a cellular α2δ subunit triple-knockout/knockdown model, we demonstrate a failure in presynaptic differentiation evidenced by defective presynaptic calcium channel clustering and calcium influx, smaller presynaptic active zones, and a strongly reduced accumulation of presynaptic vesicle-associated proteins (synapsin and vGLUT). The presynaptic defect is associated with the downscaling of postsynaptic AMPA receptors and the postsynaptic density. The role of α2δ isoforms as synaptic organizers is highly redundant, as each individual α2δ isoform can rescue presynaptic calcium channel trafficking and expression of synaptic proteins. Moreover, α2δ-2 and α2δ-3 with mutated metal ion-dependent adhesion sites can fully rescue presynaptic synapsin expression but only partially calcium channel trafficking, suggesting that the regulatory role of α2δ subunits is independent from its role as a calcium channel subunit. Our findings influence the current view on excitatory synapse formation. First, our study suggests that postsynaptic differentiation is secondary to presynaptic differentiation. Second, the dependence of presynaptic differentiation on α2δ implicates α2δ subunits as potential nucleation points for the organization of synapses. Finally, our results suggest that α2δ subunits act as transsynaptic organizers of glutamatergic synapses, thereby aligning the synaptic active zone with the postsynaptic density.","lang":"eng"}],"type":"journal_article"},{"month":"06","publication_identifier":{"eissn":["10959564"],"issn":["10747427"]},"tmp":{"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)","image":"/images/cc_by_nc_nd.png"},"oa":1,"external_id":{"pmid":["34214666"],"isi":["000677694900004"]},"isi":1,"quality_controlled":"1","project":[{"call_identifier":"H2020","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","_id":"25CA28EA-B435-11E9-9278-68D0E5697425","grant_number":"694539"}],"doi":"10.1016/j.nlm.2021.107486","language":[{"iso":"eng"}],"article_number":"107486","file_date_updated":"2021-07-19T13:46:06Z","ec_funded":1,"acknowledgement":"This work was supported by a European Research Council Advanced Grant 694539 to Ryuichi Shigemoto.","year":"2021","pmid":1,"publication_status":"published","department":[{"_id":"RySh"}],"publisher":"Elsevier","author":[{"first_name":"Felipe","last_name":"Fredes","full_name":"Fredes, Felipe"},{"full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444"}],"date_created":"2021-07-11T22:01:16Z","date_updated":"2023-08-10T14:10:37Z","volume":183,"scopus_import":"1","day":"30","has_accepted_license":"1","article_processing_charge":"No","publication":"Neurobiology of Learning and Memory","citation":{"chicago":"Fredes, Felipe, and Ryuichi Shigemoto. “The Role of Hippocampal Mossy Cells in Novelty Detection.” Neurobiology of Learning and Memory. Elsevier, 2021. https://doi.org/10.1016/j.nlm.2021.107486.","mla":"Fredes, Felipe, and Ryuichi Shigemoto. “The Role of Hippocampal Mossy Cells in Novelty Detection.” Neurobiology of Learning and Memory, vol. 183, 107486, Elsevier, 2021, doi:10.1016/j.nlm.2021.107486.","short":"F. Fredes, R. Shigemoto, Neurobiology of Learning and Memory 183 (2021).","ista":"Fredes F, Shigemoto R. 2021. The role of hippocampal mossy cells in novelty detection. Neurobiology of Learning and Memory. 183, 107486.","ieee":"F. Fredes and R. Shigemoto, “The role of hippocampal mossy cells in novelty detection,” Neurobiology of Learning and Memory, vol. 183. Elsevier, 2021.","apa":"Fredes, F., & Shigemoto, R. (2021). The role of hippocampal mossy cells in novelty detection. Neurobiology of Learning and Memory. Elsevier. https://doi.org/10.1016/j.nlm.2021.107486","ama":"Fredes F, Shigemoto R. The role of hippocampal mossy cells in novelty detection. Neurobiology of Learning and Memory. 2021;183. doi:10.1016/j.nlm.2021.107486"},"article_type":"original","date_published":"2021-06-30T00:00:00Z","type":"journal_article","abstract":[{"text":"At the encounter with a novel environment, contextual memory formation is greatly enhanced, accompanied with increased arousal and active exploration. Although this phenomenon has been widely observed in animal and human daily life, how the novelty in the environment is detected and contributes to contextual memory formation has lately started to be unveiled. The hippocampus has been studied for many decades for its largely known roles in encoding spatial memory, and a growing body of evidence indicates a differential involvement of dorsal and ventral hippocampal divisions in novelty detection. In this brief review article, we discuss the recent findings of the role of mossy cells in the ventral hippocampal moiety in novelty detection and put them in perspective with other novelty-related pathways in the hippocampus. We propose a mechanism for novelty-driven memory acquisition in the dentate gyrus by the direct projection of ventral mossy cells to dorsal dentate granule cells. By this projection, the ventral hippocampus sends novelty signals to the dorsal hippocampus, opening a gate for memory encoding in dentate granule cells based on information coming from the entorhinal cortex. We conclude that, contrary to the presently accepted functional independence, the dorsal and ventral hippocampi cooperate to link the novelty and contextual information, and this dorso-ventral interaction is crucial for the novelty-dependent memory formation.","lang":"eng"}],"_id":"9641","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ddc":["610"],"title":"The role of hippocampal mossy cells in novelty detection","status":"public","intvolume":" 183","oa_version":"Published Version","file":[{"date_updated":"2021-07-19T13:46:06Z","date_created":"2021-07-19T13:46:06Z","success":1,"checksum":"8e8298a9e8c7df146ad23f32c2a63929","file_id":"9694","relation":"main_file","creator":"cziletti","file_size":1994793,"content_type":"application/pdf","file_name":"2021_NeurobLearnMemory_Fredes.pdf","access_level":"open_access"}]},{"file_date_updated":"2022-05-31T09:10:15Z","author":[{"first_name":"Tanvi","last_name":"Butola","full_name":"Butola, Tanvi"},{"full_name":"Alvanos, Theocharis","last_name":"Alvanos","first_name":"Theocharis"},{"full_name":"Hintze, Anika","last_name":"Hintze","first_name":"Anika"},{"full_name":"Koppensteiner, Peter","orcid":"0000-0002-3509-1948","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","last_name":"Koppensteiner","first_name":"Peter"},{"last_name":"Kleindienst","first_name":"David","id":"42E121A4-F248-11E8-B48F-1D18A9856A87","full_name":"Kleindienst, David"},{"full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto","first_name":"Ryuichi"},{"full_name":"Wichmann, Carolin","last_name":"Wichmann","first_name":"Carolin"},{"full_name":"Moser, Tobias","last_name":"Moser","first_name":"Tobias"}],"volume":41,"date_created":"2021-09-27T14:33:13Z","date_updated":"2023-08-14T06:56:30Z","pmid":1,"year":"2021","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.","publisher":"Society for Neuroscience","department":[{"_id":"RySh"}],"publication_status":"published","publication_identifier":{"issn":["0270-6474"],"eissn":["1529-2401"]},"month":"09","doi":"10.1523/JNEUROSCI.0586-21.2021","language":[{"iso":"eng"}],"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","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"pmid":["34353898"],"isi":["000752287700005"]},"oa":1,"quality_controlled":"1","isi":1,"issue":"37","abstract":[{"lang":"eng","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."}],"type":"journal_article","oa_version":"Published Version","file":[{"file_name":"2021_JourNeuroscience_Butola.pdf","access_level":"open_access","file_size":11571961,"content_type":"application/pdf","creator":"dernst","relation":"main_file","file_id":"11423","date_updated":"2022-05-31T09:10:15Z","date_created":"2022-05-31T09:10:15Z","checksum":"769ab627c7355a50ccfd445e43a5f351","success":1}],"_id":"10051","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":" 41","title":"RIM-binding protein 2 organizes Ca21 channel topography and regulates release probability and vesicle replenishment at a fast central synapse","ddc":["570"],"status":"public","article_processing_charge":"No","has_accepted_license":"1","day":"15","scopus_import":"1","date_published":"2021-09-15T00:00:00Z","citation":{"short":"T. Butola, T. Alvanos, A. Hintze, P. Koppensteiner, D. Kleindienst, R. Shigemoto, C. Wichmann, T. Moser, Journal of Neuroscience 41 (2021) 7742–7767.","mla":"Butola, Tanvi, et al. “RIM-Binding Protein 2 Organizes Ca21 Channel Topography and Regulates Release Probability and Vesicle Replenishment at a Fast Central Synapse.” Journal of Neuroscience, vol. 41, no. 37, Society for Neuroscience, 2021, pp. 7742–67, doi:10.1523/JNEUROSCI.0586-21.2021.","chicago":"Butola, Tanvi, Theocharis Alvanos, Anika Hintze, Peter Koppensteiner, David Kleindienst, Ryuichi Shigemoto, Carolin Wichmann, and Tobias Moser. “RIM-Binding Protein 2 Organizes Ca21 Channel Topography and Regulates Release Probability and Vesicle Replenishment at a Fast Central Synapse.” Journal of Neuroscience. Society for Neuroscience, 2021. https://doi.org/10.1523/JNEUROSCI.0586-21.2021.","ama":"Butola T, Alvanos T, Hintze A, et al. RIM-binding protein 2 organizes Ca21 channel topography and regulates release probability and vesicle replenishment at a fast central synapse. Journal of Neuroscience. 2021;41(37):7742-7767. doi:10.1523/JNEUROSCI.0586-21.2021","ieee":"T. Butola et al., “RIM-binding protein 2 organizes Ca21 channel topography and regulates release probability and vesicle replenishment at a fast central synapse,” Journal of Neuroscience, vol. 41, no. 37. Society for Neuroscience, pp. 7742–7767, 2021.","apa":"Butola, T., Alvanos, T., Hintze, A., Koppensteiner, P., Kleindienst, D., Shigemoto, R., … Moser, T. (2021). RIM-binding protein 2 organizes Ca21 channel topography and regulates release probability and vesicle replenishment at a fast central synapse. Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.0586-21.2021","ista":"Butola T, Alvanos T, Hintze A, Koppensteiner P, Kleindienst D, Shigemoto R, Wichmann C, Moser T. 2021. RIM-binding protein 2 organizes Ca21 channel topography and regulates release probability and vesicle replenishment at a fast central synapse. Journal of Neuroscience. 41(37), 7742–7767."},"publication":"Journal of Neuroscience","page":"7742-7767","article_type":"original"},{"doi":"10.7554/eLife.65954","language":[{"iso":"eng"}],"external_id":{"isi":["000715789500001"]},"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","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"quality_controlled":"1","isi":1,"month":"11","publication_identifier":{"eissn":["2050-084X"]},"author":[{"full_name":"Biane, Celia","last_name":"Biane","first_name":"Celia"},{"last_name":"Rückerl","first_name":"Florian","full_name":"Rückerl, Florian"},{"full_name":"Abrahamsson, Therese","first_name":"Therese","last_name":"Abrahamsson"},{"last_name":"Saint-Cloment","first_name":"Cécile","full_name":"Saint-Cloment, Cécile"},{"full_name":"Mariani, Jean","first_name":"Jean","last_name":"Mariani"},{"last_name":"Shigemoto","first_name":"Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi"},{"full_name":"Digregorio, David A.","last_name":"Digregorio","first_name":"David A."},{"first_name":"Rachel M.","last_name":"Sherrard","full_name":"Sherrard, Rachel M."},{"full_name":"Cathala, Laurence","last_name":"Cathala","first_name":"Laurence"}],"date_created":"2021-12-05T23:01:40Z","date_updated":"2023-08-14T13:12:07Z","volume":10,"acknowledgement":"This study was supported by the Centre National de la Recherche Scientifique and the Agence Nationale de la Recherche (ANR-13-BSV4-00166, to LC and DAD). TA was supported by fellowships from the Fondation pour la Recherche Medicale and the Swedish Research Council. We thank Dmitry Ershov from the Image Analysis Hub of the Institut Pasteur, Elodie Le Monnier, Elena Hollergschwandtner, Vanessa Zheden, and Corinne Nantet for technical support and Haining Zhong for providing the Venus-tagged PSD95 mouse line. We would like to thank Alberto Bacci, Ann Lohof, and Nelson Rebola for comments on the manuscript.","year":"2021","publication_status":"published","department":[{"_id":"RySh"}],"publisher":"eLife Sciences Publications","file_date_updated":"2021-12-10T08:31:41Z","article_number":"e65954","date_published":"2021-11-03T00:00:00Z","publication":"eLife","citation":{"ieee":"C. Biane et al., “Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons,” eLife, vol. 10. eLife Sciences Publications, 2021.","apa":"Biane, C., Rückerl, F., Abrahamsson, T., Saint-Cloment, C., Mariani, J., Shigemoto, R., … Cathala, L. (2021). Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.65954","ista":"Biane C, Rückerl F, Abrahamsson T, Saint-Cloment C, Mariani J, Shigemoto R, Digregorio DA, Sherrard RM, Cathala L. 2021. Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons. eLife. 10, e65954.","ama":"Biane C, Rückerl F, Abrahamsson T, et al. Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons. eLife. 2021;10. doi:10.7554/eLife.65954","chicago":"Biane, Celia, Florian Rückerl, Therese Abrahamsson, Cécile Saint-Cloment, Jean Mariani, Ryuichi Shigemoto, David A. Digregorio, Rachel M. Sherrard, and Laurence Cathala. “Developmental Emergence of Two-Stage Nonlinear Synaptic Integration in Cerebellar Interneurons.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/eLife.65954.","short":"C. Biane, F. Rückerl, T. Abrahamsson, C. Saint-Cloment, J. Mariani, R. Shigemoto, D.A. Digregorio, R.M. Sherrard, L. Cathala, ELife 10 (2021).","mla":"Biane, Celia, et al. “Developmental Emergence of Two-Stage Nonlinear Synaptic Integration in Cerebellar Interneurons.” ELife, vol. 10, e65954, eLife Sciences Publications, 2021, doi:10.7554/eLife.65954."},"article_type":"original","day":"03","article_processing_charge":"No","has_accepted_license":"1","scopus_import":"1","file":[{"content_type":"application/pdf","file_size":13131322,"creator":"cchlebak","access_level":"open_access","file_name":"2021_eLife_Biane.pdf","checksum":"c7c33c3319428d56e332e22349c50ed3","success":1,"date_updated":"2021-12-10T08:31:41Z","date_created":"2021-12-10T08:31:41Z","relation":"main_file","file_id":"10528"}],"oa_version":"Published Version","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"10403","status":"public","title":"Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons","ddc":["570"],"intvolume":" 10","abstract":[{"lang":"eng","text":"Synaptic transmission, connectivity, and dendritic morphology mature in parallel during brain development and are often disrupted in neurodevelopmental disorders. Yet how these changes influence the neuronal computations necessary for normal brain function are not well understood. To identify cellular mechanisms underlying the maturation of synaptic integration in interneurons, we combined patch-clamp recordings of excitatory inputs in mouse cerebellar stellate cells (SCs), three-dimensional reconstruction of SC morphology with excitatory synapse location, and biophysical modeling. We found that postnatal maturation of postsynaptic strength was homogeneously reduced along the somatodendritic axis, but dendritic integration was always sublinear. However, dendritic branching increased without changes in synapse density, leading to a substantial gain in distal inputs. Thus, changes in synapse distribution, rather than dendrite cable properties, are the dominant mechanism underlying the maturation of neuronal computation. These mechanisms favor the emergence of a spatially compartmentalized two-stage integration model promoting location-dependent integration within dendritic subunits."}],"type":"journal_article"}]