[{"language":[{"iso":"eng"}],"doi":"10.1016/j.cub.2020.09.074","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"}],"quality_controlled":"1","isi":1,"external_id":{"isi":["000614361000020"]},"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,"month":"01","volume":31,"date_updated":"2023-08-04T10:47:11Z","date_created":"2020-02-28T10:56:18Z","related_material":{"link":[{"relation":"press_release","description":"News on IST Homepage","url":"https://ist.ac.at/en/news/remembering-novelty/"}]},"author":[{"full_name":"Fredes Tolorza, Felipe A","last_name":"Fredes Tolorza","first_name":"Felipe A","id":"384825DA-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Silva Sifuentes, Maria A","id":"371B3D6E-F248-11E8-B48F-1D18A9856A87","first_name":"Maria A","last_name":"Silva Sifuentes"},{"id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","first_name":"Peter","last_name":"Koppensteiner","full_name":"Koppensteiner, Peter"},{"first_name":"Kenta","last_name":"Kobayashi","full_name":"Kobayashi, Kenta"},{"first_name":"Maximilian A","last_name":"Jösch","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3937-1330","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"}],"publisher":"Elsevier","department":[{"_id":"MaJö"},{"_id":"RySh"}],"publication_status":"published","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","ec_funded":1,"file_date_updated":"2020-10-19T13:31:28Z","date_published":"2021-01-11T00:00:00Z","page":"P25-38.E5","article_type":"original","citation":{"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","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.","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.","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","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.","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."},"publication":"Current Biology","article_processing_charge":"No","has_accepted_license":"1","day":"11","oa_version":"Published Version","file":[{"file_name":"2021_CurrentBiology_Fredes.pdf","access_level":"open_access","creator":"dernst","content_type":"application/pdf","file_size":4915964,"file_id":"8678","relation":"main_file","date_updated":"2020-10-19T13:31:28Z","date_created":"2020-10-19T13:31:28Z","success":1,"checksum":"b7b9c8bc84a08befce365c675229a7d1"}],"intvolume":" 31","ddc":["570"],"status":"public","title":"Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"7551","issue":"1","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"}],"type":"journal_article"},{"scopus_import":"1","has_accepted_license":"1","article_processing_charge":"No","day":"06","article_type":"original","citation":{"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","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).","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","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.","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).","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."},"publication":"PNAS","date_published":"2021-04-06T00:00:00Z","type":"journal_article","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"}],"intvolume":" 118","status":"public","title":"Presynaptic α2δ subunits are key organizers of glutamatergic synapses","ddc":["570"],"_id":"9330","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"Published Version","file":[{"access_level":"open_access","file_name":"2021_PNAS_Schoepf.pdf","content_type":"application/pdf","file_size":2603911,"creator":"dernst","relation":"main_file","file_id":"9340","checksum":"dd014f68ae9d7d8d8fc4139a24e04506","success":1,"date_updated":"2021-04-19T10:10:56Z","date_created":"2021-04-19T10:10:56Z"}],"publication_identifier":{"eissn":["1091-6490"]},"month":"04","project":[{"grant_number":"694539","_id":"25CA28EA-B435-11E9-9278-68D0E5697425","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","call_identifier":"H2020"}],"isi":1,"quality_controlled":"1","external_id":{"isi":["000637398300002"]},"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,"language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"EM-Fac"}],"doi":"10.1073/pnas.1920827118","ec_funded":1,"file_date_updated":"2021-04-19T10:10:56Z","department":[{"_id":"EM-Fac"},{"_id":"RySh"}],"publisher":"National Academy of Sciences","publication_status":"published","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","volume":118,"date_updated":"2023-08-08T13:08:47Z","date_created":"2021-04-18T22:01:40Z","author":[{"first_name":"Clemens L.","last_name":"Schöpf","full_name":"Schöpf, Clemens L."},{"last_name":"Ablinger","first_name":"Cornelia","full_name":"Ablinger, Cornelia"},{"full_name":"Geisler, Stefanie M.","last_name":"Geisler","first_name":"Stefanie M."},{"full_name":"Stanika, Ruslan I.","first_name":"Ruslan I.","last_name":"Stanika"},{"full_name":"Campiglio, Marta","last_name":"Campiglio","first_name":"Marta"},{"full_name":"Kaufmann, Walter","orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","last_name":"Kaufmann","first_name":"Walter"},{"last_name":"Nimmervoll","first_name":"Benedikt","full_name":"Nimmervoll, Benedikt"},{"first_name":"Bettina","last_name":"Schlick","full_name":"Schlick, Bettina"},{"full_name":"Brockhaus, Johannes","first_name":"Johannes","last_name":"Brockhaus"},{"full_name":"Missler, Markus","last_name":"Missler","first_name":"Markus"},{"full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","first_name":"Ryuichi","last_name":"Shigemoto"},{"full_name":"Obermair, Gerald J.","first_name":"Gerald J.","last_name":"Obermair"}]},{"ec_funded":1,"file_date_updated":"2021-07-19T13:46:06Z","article_number":"107486","author":[{"full_name":"Fredes, Felipe","first_name":"Felipe","last_name":"Fredes"},{"full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","first_name":"Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87"}],"volume":183,"date_created":"2021-07-11T22:01:16Z","date_updated":"2023-08-10T14:10:37Z","pmid":1,"year":"2021","acknowledgement":"This work was supported by a European Research Council Advanced Grant 694539 to Ryuichi Shigemoto.","publisher":"Elsevier","department":[{"_id":"RySh"}],"publication_status":"published","publication_identifier":{"eissn":["10959564"],"issn":["10747427"]},"month":"06","doi":"10.1016/j.nlm.2021.107486","language":[{"iso":"eng"}],"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":{"pmid":["34214666"],"isi":["000677694900004"]},"oa":1,"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"}],"isi":1,"quality_controlled":"1","abstract":[{"lang":"eng","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."}],"type":"journal_article","oa_version":"Published Version","file":[{"relation":"main_file","file_id":"9694","date_created":"2021-07-19T13:46:06Z","date_updated":"2021-07-19T13:46:06Z","checksum":"8e8298a9e8c7df146ad23f32c2a63929","success":1,"file_name":"2021_NeurobLearnMemory_Fredes.pdf","access_level":"open_access","content_type":"application/pdf","file_size":1994793,"creator":"cziletti"}],"_id":"9641","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":" 183","ddc":["610"],"title":"The role of hippocampal mossy cells in novelty detection","status":"public","article_processing_charge":"No","has_accepted_license":"1","day":"30","scopus_import":"1","date_published":"2021-06-30T00:00:00Z","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.","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","ieee":"F. Fredes and R. Shigemoto, “The role of hippocampal mossy cells in novelty detection,” Neurobiology of Learning and Memory, vol. 183. Elsevier, 2021.","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"},"publication":"Neurobiology of Learning and Memory","article_type":"original"},{"file_date_updated":"2022-05-31T09:10:15Z","author":[{"full_name":"Butola, Tanvi","first_name":"Tanvi","last_name":"Butola"},{"last_name":"Alvanos","first_name":"Theocharis","full_name":"Alvanos, Theocharis"},{"first_name":"Anika","last_name":"Hintze","full_name":"Hintze, Anika"},{"full_name":"Koppensteiner, Peter","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3509-1948","first_name":"Peter","last_name":"Koppensteiner"},{"id":"42E121A4-F248-11E8-B48F-1D18A9856A87","last_name":"Kleindienst","first_name":"David","full_name":"Kleindienst, David"},{"last_name":"Shigemoto","first_name":"Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi"},{"last_name":"Wichmann","first_name":"Carolin","full_name":"Wichmann, Carolin"},{"last_name":"Moser","first_name":"Tobias","full_name":"Moser, Tobias"}],"date_updated":"2023-08-14T06:56:30Z","date_created":"2021-09-27T14:33:13Z","volume":41,"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.","pmid":1,"publication_status":"published","publisher":"Society for Neuroscience","department":[{"_id":"RySh"}],"month":"09","publication_identifier":{"eissn":["1529-2401"],"issn":["0270-6474"]},"doi":"10.1523/JNEUROSCI.0586-21.2021","language":[{"iso":"eng"}],"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":{"pmid":["34353898"],"isi":["000752287700005"]},"isi":1,"quality_controlled":"1","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"}],"issue":"37","type":"journal_article","oa_version":"Published Version","file":[{"checksum":"769ab627c7355a50ccfd445e43a5f351","success":1,"date_created":"2022-05-31T09:10:15Z","date_updated":"2022-05-31T09:10:15Z","relation":"main_file","file_id":"11423","file_size":11571961,"content_type":"application/pdf","creator":"dernst","access_level":"open_access","file_name":"2021_JourNeuroscience_Butola.pdf"}],"_id":"10051","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","status":"public","title":"RIM-binding protein 2 organizes Ca21 channel topography and regulates release probability and vesicle replenishment at a fast central synapse","ddc":["570"],"intvolume":" 41","day":"15","article_processing_charge":"No","has_accepted_license":"1","scopus_import":"1","date_published":"2021-09-15T00:00:00Z","publication":"Journal of Neuroscience","citation":{"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.","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","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.","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","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.","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.","short":"T. Butola, T. Alvanos, A. Hintze, P. Koppensteiner, D. Kleindienst, R. Shigemoto, C. Wichmann, T. Moser, Journal of Neuroscience 41 (2021) 7742–7767."},"article_type":"original","page":"7742-7767"},{"month":"11","publication_identifier":{"eissn":["2050-084X"]},"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":["000715789500001"]},"quality_controlled":"1","isi":1,"doi":"10.7554/eLife.65954","language":[{"iso":"eng"}],"article_number":"e65954","file_date_updated":"2021-12-10T08:31:41Z","year":"2021","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.","publication_status":"published","department":[{"_id":"RySh"}],"publisher":"eLife Sciences Publications","author":[{"first_name":"Celia","last_name":"Biane","full_name":"Biane, Celia"},{"full_name":"Rückerl, Florian","last_name":"Rückerl","first_name":"Florian"},{"full_name":"Abrahamsson, Therese","first_name":"Therese","last_name":"Abrahamsson"},{"first_name":"Cécile","last_name":"Saint-Cloment","full_name":"Saint-Cloment, Cécile"},{"last_name":"Mariani","first_name":"Jean","full_name":"Mariani, Jean"},{"first_name":"Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi"},{"first_name":"David A.","last_name":"Digregorio","full_name":"Digregorio, David A."},{"first_name":"Rachel M.","last_name":"Sherrard","full_name":"Sherrard, Rachel M."},{"last_name":"Cathala","first_name":"Laurence","full_name":"Cathala, Laurence"}],"date_updated":"2023-08-14T13:12:07Z","date_created":"2021-12-05T23:01:40Z","volume":10,"scopus_import":"1","day":"03","has_accepted_license":"1","article_processing_charge":"No","publication":"eLife","citation":{"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.","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.","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).","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.","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","ieee":"C. Biane et al., “Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons,” eLife, vol. 10. eLife Sciences Publications, 2021.","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"},"article_type":"original","date_published":"2021-11-03T00:00:00Z","type":"journal_article","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."}],"_id":"10403","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","status":"public","ddc":["570"],"title":"Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons","intvolume":" 10","oa_version":"Published Version","file":[{"access_level":"open_access","file_name":"2021_eLife_Biane.pdf","file_size":13131322,"content_type":"application/pdf","creator":"cchlebak","relation":"main_file","file_id":"10528","checksum":"c7c33c3319428d56e332e22349c50ed3","success":1,"date_updated":"2021-12-10T08:31:41Z","date_created":"2021-12-10T08:31:41Z"}]},{"publication_identifier":{"eissn":["2050-084X"]},"month":"04","language":[{"iso":"eng"}],"doi":"10.7554/ELIFE.68274","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"},{"name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","name":"International IST Doctoral Program","call_identifier":"H2020"}],"quality_controlled":"1","isi":1,"external_id":{"isi":["000651761700001"]},"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,"ec_funded":1,"file_date_updated":"2021-05-31T09:43:09Z","article_number":"e68274","volume":10,"date_created":"2021-05-30T22:01:23Z","date_updated":"2024-03-28T23:30:31Z","related_material":{"link":[{"relation":"earlier_version","url":"https://doi.org/10.1101/2020.04.16.045112"}],"record":[{"status":"public","relation":"dissertation_contains","id":"9562"}]},"author":[{"full_name":"Bhandari, Pradeep","first_name":"Pradeep","last_name":"Bhandari","id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0863-4481"},{"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":"Fernández-Fernández","first_name":"Diego","full_name":"Fernández-Fernández, Diego"},{"full_name":"Fritzius, Thorsten","first_name":"Thorsten","last_name":"Fritzius"},{"last_name":"Kleindienst","first_name":"David","id":"42E121A4-F248-11E8-B48F-1D18A9856A87","full_name":"Kleindienst, David"},{"full_name":"Önal, Hüseyin C","orcid":"0000-0002-2771-2011","id":"4659D740-F248-11E8-B48F-1D18A9856A87","last_name":"Önal","first_name":"Hüseyin C"},{"full_name":"Montanaro-Punzengruber, Jacqueline-Claire","first_name":"Jacqueline-Claire","last_name":"Montanaro-Punzengruber","id":"3786AB44-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Gassmann","first_name":"Martin","full_name":"Gassmann, Martin"},{"first_name":"Peter M","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M"},{"last_name":"Kulik","first_name":"Akos","full_name":"Kulik, Akos"},{"full_name":"Bettler, Bernhard","last_name":"Bettler","first_name":"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","last_name":"Koppensteiner","first_name":"Peter","orcid":"0000-0002-3509-1948","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87"}],"department":[{"_id":"RySh"},{"_id":"PeJo"}],"publisher":"eLife Sciences Publications","publication_status":"published","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","article_processing_charge":"No","has_accepted_license":"1","day":"29","scopus_import":"1","date_published":"2021-04-29T00:00:00Z","article_type":"original","citation":{"ama":"Bhandari P, Vandael DH, Fernández-Fernández D, et al. GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. eLife. 2021;10. doi:10.7554/ELIFE.68274","apa":"Bhandari, P., Vandael, D. H., Fernández-Fernández, D., Fritzius, T., Kleindienst, D., Önal, H. C., … Koppensteiner, P. (2021). GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. ELife. eLife Sciences Publications. https://doi.org/10.7554/ELIFE.68274","ieee":"P. Bhandari et al., “GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals,” eLife, vol. 10. eLife Sciences Publications, 2021.","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.","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).","mla":"Bhandari, Pradeep, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from Medial Habenula Terminals.” ELife, vol. 10, e68274, eLife Sciences Publications, 2021, doi:10.7554/ELIFE.68274.","chicago":"Bhandari, Pradeep, David H Vandael, Diego Fernández-Fernández, Thorsten Fritzius, David Kleindienst, Hüseyin C Önal, Jacqueline-Claire Montanaro-Punzengruber, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from Medial Habenula Terminals.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/ELIFE.68274."},"publication":"eLife","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"}],"type":"journal_article","file":[{"access_level":"open_access","file_name":"2021_eLife_Bhandari.pdf","file_size":8174719,"content_type":"application/pdf","creator":"cziletti","relation":"main_file","file_id":"9440","checksum":"6ebcb79999f889766f7cd79ee134ad28","success":1,"date_created":"2021-05-31T09:43:09Z","date_updated":"2021-05-31T09:43:09Z"}],"oa_version":"Published Version","intvolume":" 10","ddc":["570"],"status":"public","title":"GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"9437"},{"_id":"9562","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","ddc":["570"],"status":"public","title":"2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning","oa_version":"Published Version","file":[{"relation":"main_file","file_id":"9563","embargo":"2022-07-01","date_updated":"2022-07-02T22:30:04Z","date_created":"2021-06-17T14:03:14Z","checksum":"659df5518db495f679cb1df9e9bd1d94","file_name":"Thesis.pdf","access_level":"open_access","file_size":77299142,"content_type":"application/pdf","creator":"dkleindienst"},{"file_size":369804895,"content_type":"application/zip","creator":"dkleindienst","embargo_to":"open_access","file_name":"Thesis_source.zip","access_level":"closed","date_updated":"2022-07-02T22:30:04Z","date_created":"2021-06-17T14:04:30Z","checksum":"3bcf63a2b19e5b6663be051bea332748","relation":"source_file","file_id":"9564"}],"type":"dissertation","alternative_title":["ISTA Thesis"],"abstract":[{"lang":"eng","text":"Left-right asymmetries can be considered a fundamental organizational principle of the vertebrate central nervous system. The hippocampal CA3-CA1 pyramidal cell synaptic connection shows an input-side dependent asymmetry where the hemispheric location of the presynaptic CA3 neuron determines the synaptic properties. Left-input synapses terminating on apical dendrites in stratum radiatum have a higher density of NMDA receptor subunit GluN2B, a lower density of AMPA receptor subunit GluA1 and smaller areas with less often perforated PSDs. On the other hand, left-input synapses terminating on basal dendrites in stratum oriens have lower GluN2B densities than right-input ones. Apical and basal synapses further employ different signaling pathways involved in LTP. SDS-digested freeze-fracture replica labeling can visualize synaptic membrane proteins with high sensitivity and resolution, and has been used to reveal the asymmetry at the electron microscopic level. However, it requires time-consuming manual demarcation of the synaptic surface for quantitative measurements. To facilitate the analysis of replica labeling, I first developed a software named Darea, which utilizes deep-learning to automatize this demarcation. With Darea I characterized the synaptic distribution of NMDA and AMPA receptors as well as the voltage-gated Ca2+ channels in CA1 stratum radiatum and oriens. Second, I explored the role of GluN2B and its carboxy-terminus in the establishment of input-side dependent hippocampal asymmetry. In conditional knock-out mice lacking GluN2B expression in CA1 and GluN2B-2A swap mice, where GluN2B carboxy-terminus was exchanged to that of GluN2A, no significant asymmetries of GluN2B, GluA1 and PSD area were detected. We further discovered a previously unknown functional asymmetry of GluN2A, which was also lost in the swap mouse. These results demonstrate that GluN2B carboxy-terminus plays a critical role in normal formation of input-side dependent asymmetry."}],"citation":{"chicago":"Kleindienst, David. “2B or Not 2B: Hippocampal Asymmetries Mediated by NMDA Receptor Subunit GluN2B C-Terminus and High-Throughput Image Analysis by Deep-Learning.” Institute of Science and Technology Austria, 2021. https://doi.org/10.15479/at:ista:9562.","mla":"Kleindienst, David. 2B or Not 2B: Hippocampal Asymmetries Mediated by NMDA Receptor Subunit GluN2B C-Terminus and High-Throughput Image Analysis by Deep-Learning. Institute of Science and Technology Austria, 2021, doi:10.15479/at:ista:9562.","short":"D. Kleindienst, 2B or Not 2B: Hippocampal Asymmetries Mediated by NMDA Receptor Subunit GluN2B C-Terminus and High-Throughput Image Analysis by Deep-Learning, Institute of Science and Technology Austria, 2021.","ista":"Kleindienst D. 2021. 2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning. Institute of Science and Technology Austria.","apa":"Kleindienst, D. (2021). 2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:9562","ieee":"D. Kleindienst, “2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning,” Institute of Science and Technology Austria, 2021.","ama":"Kleindienst D. 2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning. 2021. doi:10.15479/at:ista:9562"},"page":"124","date_published":"2021-06-01T00:00:00Z","day":"01","has_accepted_license":"1","article_processing_charge":"No","year":"2021","publication_status":"published","publisher":"Institute of Science and Technology Austria","department":[{"_id":"GradSch"},{"_id":"RySh"}],"author":[{"first_name":"David","last_name":"Kleindienst","id":"42E121A4-F248-11E8-B48F-1D18A9856A87","full_name":"Kleindienst, David"}],"related_material":{"record":[{"id":"9756","relation":"part_of_dissertation","status":"public"},{"relation":"part_of_dissertation","status":"public","id":"9437"},{"id":"8532","status":"public","relation":"part_of_dissertation"},{"relation":"part_of_dissertation","status":"public","id":"612"}]},"date_updated":"2023-09-11T12:55:53Z","date_created":"2021-06-17T14:10:47Z","file_date_updated":"2022-07-02T22:30:04Z","oa":1,"doi":"10.15479/at:ista:9562","degree_awarded":"PhD","acknowledged_ssus":[{"_id":"EM-Fac"}],"supervisor":[{"orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto","first_name":"Ryuichi","full_name":"Shigemoto, Ryuichi"}],"language":[{"iso":"eng"}],"month":"06","publication_identifier":{"issn":["2663-337X"]}},{"place":"New York","ec_funded":1,"department":[{"_id":"RySh"},{"_id":"EM-Fac"}],"publisher":"Humana","publication_status":"published","year":"2021","acknowledgement":"This work was supported by the European Union (European Research Council Advanced grant no. 694539 and Human Brain Project Ref. 720270 to R. S.) and the Austrian Academy of Sciences (DOC fellowship to D.K.).","volume":169,"date_updated":"2024-03-28T23:30:31Z","date_created":"2021-07-30T09:34:56Z","related_material":{"record":[{"id":"9562","status":"public","relation":"dissertation_contains"}]},"author":[{"id":"3F99E422-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9735-5315","first_name":"Walter","last_name":"Kaufmann","full_name":"Kaufmann, Walter"},{"first_name":"David","last_name":"Kleindienst","id":"42E121A4-F248-11E8-B48F-1D18A9856A87","full_name":"Kleindienst, David"},{"last_name":"Harada","first_name":"Harumi","orcid":"0000-0001-7429-7896","id":"2E55CDF2-F248-11E8-B48F-1D18A9856A87","full_name":"Harada, Harumi"},{"last_name":"Shigemoto","first_name":"Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi"}],"publication_identifier":{"eisbn":["9781071615225"],"isbn":["9781071615218"]},"month":"07","project":[{"call_identifier":"H2020","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","grant_number":"694539","_id":"25CA28EA-B435-11E9-9278-68D0E5697425"},{"name":"Human Brain Project Specific Grant Agreement 1 (HBP SGA 1)","call_identifier":"H2020","grant_number":"720270","_id":"25CBA828-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","language":[{"iso":"eng"}],"doi":"10.1007/978-1-0716-1522-5_19","alternative_title":["Neuromethods"],"type":"book_chapter","abstract":[{"lang":"eng","text":"High-resolution visualization and quantification of membrane proteins contribute to the understanding of their functions and the roles they play in physiological and pathological conditions. Sodium dodecyl sulfate-digested freeze-fracture replica labeling (SDS-FRL) is a powerful electron microscopy method to study quantitatively the two-dimensional distribution of transmembrane proteins and their tightly associated proteins. During treatment with SDS, intracellular organelles and proteins not anchored to the replica are dissolved, whereas integral membrane proteins captured and stabilized by carbon/platinum deposition remain on the replica. Their intra- and extracellular domains become exposed on the surface of the replica, facilitating the accessibility of antibodies and, therefore, providing higher labeling efficiency than those obtained with other immunoelectron microscopy techniques. In this chapter, we describe the protocols of SDS-FRL adapted for mammalian brain samples, and optimization of the SDS treatment to increase the labeling efficiency for quantification of Cav2.1, the alpha subunit of P/Q-type voltage-dependent calcium channels utilizing deep learning algorithms."}],"intvolume":" 169","title":"High-Resolution localization and quantitation of membrane proteins by SDS-digested freeze-fracture replica labeling (SDS-FRL)","status":"public","ddc":["573"],"user_id":"D865714E-FA4E-11E9-B85B-F5C5E5697425","_id":"9756","oa_version":"None","series_title":"Neuromethods","keyword":["Freeze-fracture replica: Deep learning","Immunogold labeling","Integral membrane protein","Electron microscopy"],"article_processing_charge":"No","has_accepted_license":"1","day":"27","page":"267-283","citation":{"ama":"Kaufmann W, Kleindienst D, Harada H, Shigemoto R. High-Resolution localization and quantitation of membrane proteins by SDS-digested freeze-fracture replica labeling (SDS-FRL). In: Receptor and Ion Channel Detection in the Brain. Vol 169. Neuromethods. New York: Humana; 2021:267-283. doi:10.1007/978-1-0716-1522-5_19","ista":"Kaufmann W, Kleindienst D, Harada H, Shigemoto R. 2021.High-Resolution localization and quantitation of membrane proteins by SDS-digested freeze-fracture replica labeling (SDS-FRL). In: Receptor and Ion Channel Detection in the Brain. Neuromethods, vol. 169, 267–283.","apa":"Kaufmann, W., Kleindienst, D., Harada, H., & Shigemoto, R. (2021). High-Resolution localization and quantitation of membrane proteins by SDS-digested freeze-fracture replica labeling (SDS-FRL). In Receptor and Ion Channel Detection in the Brain (Vol. 169, pp. 267–283). New York: Humana. https://doi.org/10.1007/978-1-0716-1522-5_19","ieee":"W. Kaufmann, D. Kleindienst, H. Harada, and R. Shigemoto, “High-Resolution localization and quantitation of membrane proteins by SDS-digested freeze-fracture replica labeling (SDS-FRL),” in Receptor and Ion Channel Detection in the Brain, vol. 169, New York: Humana, 2021, pp. 267–283.","mla":"Kaufmann, Walter, et al. “High-Resolution Localization and Quantitation of Membrane Proteins by SDS-Digested Freeze-Fracture Replica Labeling (SDS-FRL).” Receptor and Ion Channel Detection in the Brain, vol. 169, Humana, 2021, pp. 267–83, doi:10.1007/978-1-0716-1522-5_19.","short":"W. Kaufmann, D. Kleindienst, H. Harada, R. Shigemoto, in:, Receptor and Ion Channel Detection in the Brain, Humana, New York, 2021, pp. 267–283.","chicago":"Kaufmann, Walter, David Kleindienst, Harumi Harada, and Ryuichi Shigemoto. “High-Resolution Localization and Quantitation of Membrane Proteins by SDS-Digested Freeze-Fracture Replica Labeling (SDS-FRL).” In Receptor and Ion Channel Detection in the Brain, 169:267–83. Neuromethods. New York: Humana, 2021. https://doi.org/10.1007/978-1-0716-1522-5_19."},"publication":" Receptor and Ion Channel Detection in the Brain","date_published":"2021-07-27T00:00:00Z"},{"department":[{"_id":"RySh"}],"publisher":"Wiley","publication_status":"published","pmid":1,"year":"2020","acknowledgement":"This study was supported by Grants-in-Aid for Scientific Research to K.K. (18K06813), Y.M. (17K08503, 17H0631319), and K.S. (16H04650) and a grant for Scientific Research on Innovative Areas to K.S (16H06276) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT). We thank K. Akashi, I. Watanabe-Iida, Y. Suzuki, and H. Azechi for technical assistance and advice, and H. Uchida for valuable discussions. We thank E. Kushiya,I. Yabe, C. Ohori, Y. Mochizuki, Y. Ishikawa, and N. Ishimoto for technical assistance in generating GluD1-KO mice.","volume":528,"date_created":"2019-12-04T16:09:29Z","date_updated":"2023-08-17T14:06:50Z","author":[{"full_name":"Nakamoto, Chihiro","last_name":"Nakamoto","first_name":"Chihiro"},{"last_name":"Konno","first_name":"Kohtarou","full_name":"Konno, Kohtarou"},{"first_name":"Taisuke","last_name":"Miyazaki","full_name":"Miyazaki, Taisuke"},{"full_name":"Nakatsukasa, Ena","first_name":"Ena","last_name":"Nakatsukasa"},{"first_name":"Rie","last_name":"Natsume","full_name":"Natsume, Rie"},{"first_name":"Manabu","last_name":"Abe","full_name":"Abe, Manabu"},{"first_name":"Meiko","last_name":"Kawamura","full_name":"Kawamura, Meiko"},{"last_name":"Fukazawa","first_name":"Yugo","full_name":"Fukazawa, Yugo"},{"full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","first_name":"Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Yamasaki, Miwako","last_name":"Yamasaki","first_name":"Miwako"},{"full_name":"Sakimura, Kenji","first_name":"Kenji","last_name":"Sakimura"},{"first_name":"Masahiko","last_name":"Watanabe","full_name":"Watanabe, Masahiko"}],"quality_controlled":"1","isi":1,"external_id":{"pmid":["31625608"],"isi":["000496410200001"]},"language":[{"iso":"eng"}],"doi":"10.1002/cne.24792","publication_identifier":{"issn":["0021-9967"],"eissn":["1096-9861"]},"month":"04","intvolume":" 528","title":"Expression mapping, quantification, and complex formation of GluD1 and GluD2 glutamate receptors in adult mouse brain","status":"public","ddc":["571","599"],"_id":"7148","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"None","type":"journal_article","issue":"6","abstract":[{"text":"In the cerebellum, GluD2 is exclusively expressed in Purkinje cells, where it regulates synapse formation and regeneration, synaptic plasticity, and motor learning. Delayed cognitive development in humans with GluD2 gene mutations suggests extracerebellar functions of GluD2. However, extracerebellar expression of GluD2 and its relationship with that of GluD1 are poorly understood. GluD2 mRNA and protein were widely detected, with relatively high levels observed in the olfactory glomerular layer, medial prefrontal cortex, cingulate cortex, retrosplenial granular cortex, olfactory tubercle, subiculum, striatum, lateral septum, anterodorsal thalamic nucleus, and arcuate hypothalamic nucleus. These regions were also enriched for GluD1, and many individual neurons coexpressed the two GluDs. In the retrosplenial granular cortex, GluD1 and GluD2 were selectively expressed at PSD‐95‐expressing glutamatergic synapses, and their coexpression on the same synapses was shown by SDS‐digested freeze‐fracture replica labeling. Biochemically, GluD1 and GluD2 formed coimmunoprecipitable complex formation in HEK293T cells and in the cerebral cortex and hippocampus. We further estimated the relative protein amount by quantitative immunoblotting using GluA2/GluD2 and GluA2/GluD1 chimeric proteins as standards for titration of GluD1 and GluD2 antibodies. Intriguingly, the relative amount of GluD2 was almost comparable to that of GluD1 in the postsynaptic density fraction prepared from the cerebral cortex and hippocampus. In contrast, GluD2 was overwhelmingly predominant in the cerebellum. Thus, we have determined the relative extracerebellar expression of GluD1 and GluD2 at regional, neuronal, and synaptic levels. These data provide a molecular–anatomical basis for possible competitive and cooperative interactions of GluD family members at synapses in various brain regions.","lang":"eng"}],"page":"1003-1027","article_type":"original","citation":{"ama":"Nakamoto C, Konno K, Miyazaki T, et al. Expression mapping, quantification, and complex formation of GluD1 and GluD2 glutamate receptors in adult mouse brain. Journal of Comparative Neurology. 2020;528(6):1003-1027. doi:10.1002/cne.24792","ista":"Nakamoto C, Konno K, Miyazaki T, Nakatsukasa E, Natsume R, Abe M, Kawamura M, Fukazawa Y, Shigemoto R, Yamasaki M, Sakimura K, Watanabe M. 2020. Expression mapping, quantification, and complex formation of GluD1 and GluD2 glutamate receptors in adult mouse brain. Journal of Comparative Neurology. 528(6), 1003–1027.","apa":"Nakamoto, C., Konno, K., Miyazaki, T., Nakatsukasa, E., Natsume, R., Abe, M., … Watanabe, M. (2020). Expression mapping, quantification, and complex formation of GluD1 and GluD2 glutamate receptors in adult mouse brain. Journal of Comparative Neurology. Wiley. https://doi.org/10.1002/cne.24792","ieee":"C. Nakamoto et al., “Expression mapping, quantification, and complex formation of GluD1 and GluD2 glutamate receptors in adult mouse brain,” Journal of Comparative Neurology, vol. 528, no. 6. Wiley, pp. 1003–1027, 2020.","mla":"Nakamoto, Chihiro, et al. “Expression Mapping, Quantification, and Complex Formation of GluD1 and GluD2 Glutamate Receptors in Adult Mouse Brain.” Journal of Comparative Neurology, vol. 528, no. 6, Wiley, 2020, pp. 1003–27, doi:10.1002/cne.24792.","short":"C. Nakamoto, K. Konno, T. Miyazaki, E. Nakatsukasa, R. Natsume, M. Abe, M. Kawamura, Y. Fukazawa, R. Shigemoto, M. Yamasaki, K. Sakimura, M. Watanabe, Journal of Comparative Neurology 528 (2020) 1003–1027.","chicago":"Nakamoto, Chihiro, Kohtarou Konno, Taisuke Miyazaki, Ena Nakatsukasa, Rie Natsume, Manabu Abe, Meiko Kawamura, et al. “Expression Mapping, Quantification, and Complex Formation of GluD1 and GluD2 Glutamate Receptors in Adult Mouse Brain.” Journal of Comparative Neurology. Wiley, 2020. https://doi.org/10.1002/cne.24792."},"publication":"Journal of Comparative Neurology","date_published":"2020-04-01T00:00:00Z","scopus_import":"1","has_accepted_license":"1","article_processing_charge":"No","day":"01"},{"quality_controlled":"1","isi":1,"external_id":{"isi":["000505167600013"],"pmid":["31767677"]},"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,"language":[{"iso":"eng"}],"doi":"10.1523/JNEUROSCI.1571-19.2019","month":"01","publication_identifier":{"eissn":["15292401"]},"publication_status":"published","department":[{"_id":"RySh"}],"publisher":"Society for Neuroscience","year":"2020","pmid":1,"date_updated":"2023-08-17T14:25:23Z","date_created":"2020-01-19T23:00:38Z","volume":40,"author":[{"full_name":"Piriya Ananda Babu, Lashmi","first_name":"Lashmi","last_name":"Piriya Ananda Babu"},{"first_name":"Han Ying","last_name":"Wang","full_name":"Wang, Han Ying"},{"full_name":"Eguchi, Kohgaku","first_name":"Kohgaku","last_name":"Eguchi","id":"2B7846DC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6170-2546"},{"last_name":"Guillaud","first_name":"Laurent","full_name":"Guillaud, Laurent"},{"last_name":"Takahashi","first_name":"Tomoyuki","full_name":"Takahashi, Tomoyuki"}],"file_date_updated":"2020-07-14T12:47:56Z","article_type":"original","page":"131-142","publication":"Journal of neuroscience","citation":{"short":"L. Piriya Ananda Babu, H.Y. Wang, K. Eguchi, L. Guillaud, T. Takahashi, Journal of Neuroscience 40 (2020) 131–142.","mla":"Piriya Ananda Babu, Lashmi, et al. “Microtubule and Actin Differentially Regulate Synaptic Vesicle Cycling to Maintain High-Frequency Neurotransmission.” Journal of Neuroscience, vol. 40, no. 1, Society for Neuroscience, 2020, pp. 131–42, doi:10.1523/JNEUROSCI.1571-19.2019.","chicago":"Piriya Ananda Babu, Lashmi, Han Ying Wang, Kohgaku Eguchi, Laurent Guillaud, and Tomoyuki Takahashi. “Microtubule and Actin Differentially Regulate Synaptic Vesicle Cycling to Maintain High-Frequency Neurotransmission.” Journal of Neuroscience. Society for Neuroscience, 2020. https://doi.org/10.1523/JNEUROSCI.1571-19.2019.","ama":"Piriya Ananda Babu L, Wang HY, Eguchi K, Guillaud L, Takahashi T. Microtubule and actin differentially regulate synaptic vesicle cycling to maintain high-frequency neurotransmission. Journal of neuroscience. 2020;40(1):131-142. doi:10.1523/JNEUROSCI.1571-19.2019","apa":"Piriya Ananda Babu, L., Wang, H. Y., Eguchi, K., Guillaud, L., & Takahashi, T. (2020). Microtubule and actin differentially regulate synaptic vesicle cycling to maintain high-frequency neurotransmission. Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.1571-19.2019","ieee":"L. Piriya Ananda Babu, H. Y. Wang, K. Eguchi, L. Guillaud, and T. Takahashi, “Microtubule and actin differentially regulate synaptic vesicle cycling to maintain high-frequency neurotransmission,” Journal of neuroscience, vol. 40, no. 1. Society for Neuroscience, pp. 131–142, 2020.","ista":"Piriya Ananda Babu L, Wang HY, Eguchi K, Guillaud L, Takahashi T. 2020. Microtubule and actin differentially regulate synaptic vesicle cycling to maintain high-frequency neurotransmission. Journal of neuroscience. 40(1), 131–142."},"date_published":"2020-01-02T00:00:00Z","scopus_import":"1","day":"02","article_processing_charge":"No","has_accepted_license":"1","title":"Microtubule and actin differentially regulate synaptic vesicle cycling to maintain high-frequency neurotransmission","ddc":["570"],"status":"public","intvolume":" 40","_id":"7339","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"Published Version","file":[{"access_level":"open_access","file_name":"2020_JourNeuroscience_Piriya.pdf","file_size":4460781,"content_type":"application/pdf","creator":"dernst","relation":"main_file","file_id":"7345","checksum":"92f5e8a47f454fc131fb94cd7f106e60","date_created":"2020-01-20T14:44:10Z","date_updated":"2020-07-14T12:47:56Z"}],"type":"journal_article","abstract":[{"text":"Cytoskeletal filaments such as microtubules (MTs) and filamentous actin (F-actin) dynamically support cell structure and functions. In central presynaptic terminals, F-actin is expressed along the release edge and reportedly plays diverse functional roles, but whether axonal MTs extend deep into terminals and play any physiological role remains controversial. At the calyx of Held in rats of either sex, confocal and high-resolution microscopy revealed that MTs enter deep into presynaptic terminal swellings and partially colocalize with a subset of synaptic vesicles (SVs). Electrophysiological analysis demonstrated that depolymerization of MTs specifically prolonged the slow-recovery time component of EPSCs from short-term depression induced by a train of high-frequency stimulation, whereas depolymerization of F-actin specifically prolonged the fast-recovery component. In simultaneous presynaptic and postsynaptic action potential recordings, depolymerization of MTs or F-actin significantly impaired the fidelity of high-frequency neurotransmission. We conclude that MTs and F-actin differentially contribute to slow and fast SV replenishment, thereby maintaining high-frequency neurotransmission.","lang":"eng"}],"issue":"1"}]