[{"external_id":{"pmid":["38215739"]},"status":"public","citation":{"ama":"Chen J, Kaufmann W, Chen C, et al. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. <i>Neuron</i>. doi:<a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">10.1016/j.neuron.2023.12.002</a>","mla":"Chen, JingJing, et al. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” <i>Neuron</i>, Elsevier, doi:<a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">10.1016/j.neuron.2023.12.002</a>.","ista":"Chen J, Kaufmann W, Chen C, Arai  itaru, Kim O, Shigemoto R, Jonas PM. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron.","apa":"Chen, J., Kaufmann, W., Chen, C., Arai,  itaru, Kim, O., Shigemoto, R., &#38; Jonas, P. M. (n.d.). Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">https://doi.org/10.1016/j.neuron.2023.12.002</a>","ieee":"J. Chen <i>et al.</i>, “Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse,” <i>Neuron</i>. Elsevier.","chicago":"Chen, JingJing, Walter Kaufmann, Chong Chen, itaru Arai, Olena Kim, Ryuichi Shigemoto, and Peter M Jonas. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” <i>Neuron</i>. Elsevier, n.d. <a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">https://doi.org/10.1016/j.neuron.2023.12.002</a>.","short":"J. Chen, W. Kaufmann, C. Chen,  itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas, Neuron (n.d.)."},"related_material":{"link":[{"relation":"press_release","description":"News on ISTA Website","url":"https://ista.ac.at/en/news/synapses-brought-to-the-point/"}]},"publication_status":"inpress","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"PreCl"},{"_id":"M-Shop"}],"date_published":"2024-01-11T00:00:00Z","year":"2024","acknowledgement":"We thank Drs. David DiGregorio and Erwin Neher for critically reading an earlier version of the manuscript, Ralf Schneggenburger for helpful discussions, Benjamin Suter and Katharina Lichter for support with image analysis, Chris Wojtan for advice on numerical solution of partial differential equations, Maria Reva for help with Ripley analysis, Alois Schlögl for programming, and Akari Hagiwara and Toshihisa Ohtsuka for anti-ELKS antibody. We are grateful to Florian Marr, Christina Altmutter, and Vanessa Zheden for excellent technical assistance and to Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA (Electron Microscopy Facility, Preclinical Facility, and Machine Shop). The project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 692692), the Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award; P 36232-B), all to P.J., and a DOC fellowship of the Austrian Academy of Sciences to J.-J.C.","_id":"14843","date_updated":"2024-03-05T09:31:24Z","abstract":[{"text":"The coupling between Ca2+ channels and release sensors is a key factor defining the signaling properties of a synapse. However, the coupling nanotopography at many synapses remains unknown, and it is unclear how it changes during development. To address these questions, we examined coupling at the cerebellar inhibitory basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission by paired recording and intracellular pipette perfusion revealed that the effects of exogenous Ca2+ chelators decreased during development, despite constant reliance of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked vesicles were only clustered at later developmental stages. Modeling suggested a developmental transformation from a more random to a more clustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission.","lang":"eng"}],"oa_version":"None","type":"journal_article","month":"01","date_created":"2024-01-21T23:00:56Z","project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"The Wittgenstein Prize","grant_number":"Z00312"},{"grant_number":"P36232","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","name":"Mechanisms of GABA release in hippocampal circuits"},{"name":"Development of nanodomain coupling between Ca2+ channels and release sensors at a central inhibitory synapse","_id":"26B66A3E-B435-11E9-9278-68D0E5697425","grant_number":"25383"}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1097-4199"],"issn":["0896-6273"]},"quality_controlled":"1","doi":"10.1016/j.neuron.2023.12.002","pmid":1,"department":[{"_id":"PeJo"},{"_id":"EM-Fac"},{"_id":"RySh"}],"publisher":"Elsevier","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ec_funded":1,"scopus_import":"1","article_processing_charge":"No","article_type":"original","publication":"Neuron","day":"11","author":[{"id":"2C4E65C8-F248-11E8-B48F-1D18A9856A87","full_name":"Chen, JingJing","first_name":"JingJing","last_name":"Chen"},{"first_name":"Walter","last_name":"Kaufmann","orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","full_name":"Kaufmann, Walter"},{"id":"3DFD581A-F248-11E8-B48F-1D18A9856A87","full_name":"Chen, Chong","last_name":"Chen","first_name":"Chong"},{"id":"32A73F6C-F248-11E8-B48F-1D18A9856A87","full_name":"Arai, Itaru","last_name":"Arai","first_name":"Itaru"},{"full_name":"Kim, Olena","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","first_name":"Olena","last_name":"Kim"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","first_name":"Ryuichi"},{"last_name":"Jonas","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M"}],"title":"Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse"},{"project":[{"_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","name":"Molecular Mechanisms of Neural Stem Cell Lineage Progression","grant_number":"F07805"}],"language":[{"iso":"eng"}],"issue":"2","publication_identifier":{"issnl":["1234-5678"],"eisbn":["1234995621"],"issn":["0896-6273"]},"quality_controlled":"1","doi":"10.1016/j.neuron.2023.11.009","pmid":1,"department":[{"_id":"SiHi"},{"_id":"RySh"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Elsevier","scopus_import":"1","article_processing_charge":"Yes (via OA deal)","article_type":"comment","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"publication":"Neuron","day":"17","file":[{"date_created":"2024-02-06T13:56:15Z","access_level":"open_access","file_id":"14944","date_updated":"2024-02-06T13:56:15Z","checksum":"32b3788f7085cf44a84108d8faaff3ce","file_size":5942467,"relation":"main_file","content_type":"application/pdf","creator":"dernst","file_name":"2024_Neuron_Cheung.pdf","success":1}],"author":[{"full_name":"Cheung, Giselle T","orcid":"0000-0001-8457-2572","id":"471195F6-F248-11E8-B48F-1D18A9856A87","last_name":"Cheung","first_name":"Giselle T"},{"last_name":"Pauler","first_name":"Florian","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7462-0048"},{"first_name":"Peter","last_name":"Koppensteiner","full_name":"Koppensteiner, Peter","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3509-1948"},{"first_name":"Thomas","last_name":"Krausgruber","full_name":"Krausgruber, Thomas"},{"id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen","first_name":"Carmen","last_name":"Streicher"},{"full_name":"Schrammel, Martin","id":"f13e7cae-e8bd-11ed-841a-96dedf69f46d","last_name":"Schrammel","first_name":"Martin"},{"first_name":"Natalie Y","last_name":"Özgen","id":"e68ece33-f6e0-11ea-865d-ae1031dcc090","full_name":"Özgen, Natalie Y"},{"id":"1d144691-e8be-11ed-9b33-bdd3077fad4c","full_name":"Ivec, Alexis","first_name":"Alexis","last_name":"Ivec"},{"full_name":"Bock, Christoph","first_name":"Christoph","last_name":"Bock"},{"first_name":"Ryuichi","last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444"},{"first_name":"Simon","last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061"}],"title":"Multipotent progenitors instruct ontogeny of the superior colliculus","external_id":{"pmid":["38096816"]},"status":"public","related_material":{"link":[{"relation":"press_release","url":"https://ista.ac.at/en/news/the-pedigree-of-brain-cells/","description":"News on ISTA Website"}]},"intvolume":"       112","has_accepted_license":"1","oa":1,"publication_status":"published","acknowledged_ssus":[{"_id":"Bio"},{"_id":"M-Shop"},{"_id":"LifeSc"},{"_id":"PreCl"}],"ddc":["570"],"date_published":"2024-01-17T00:00:00Z","year":"2024","acknowledgement":"We thank Liqun Luo for his continued support, for providing essential resources for generating Fzd10-CreER mice which were generated in his laboratory, and for comments on the manuscript; W. Zhong for providing Nestin-Cre transgenic mouse line for this study; A. Heger for mouse colony management; R. Beattie and T. Asenov for designing and producing components of acute slice recovery chamber for MADM-CloneSeq experiments; and K. Leopold, J. Rodarte and N. Amberg for initial experiments, technical support and/or assistance. This study was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Imaging & Optics Facility (IOF), Laboratory Support Facility (LSF), Miba Machine Shop, and Pre-clinical Facility (PCF). G.C. received funding from European Commission (IST plus postdoctoral fellowship). This work was supported by ISTA institutional\r\nfunds; the Austrian Science Fund Special Research Programmes (FWF SFB F78 Neuro Stem Modulation) to S.H. ","_id":"12875","date_updated":"2025-05-14T09:39:37Z","abstract":[{"text":"The superior colliculus (SC) in the mammalian midbrain is essential for multisensory integration and is composed of a rich diversity of excitatory and inhibitory neurons and glia. However, the developmental principles directing the generation of SC cell-type diversity are not understood. Here, we pursued systematic cell lineage tracing in silico and in vivo, preserving full spatial information, using genetic mosaic analysis with double markers (MADM)-based clonal analysis with single-cell sequencing (MADM-CloneSeq). The analysis of clonally related cell lineages revealed that radial glial progenitors (RGPs) in SC are exceptionally multipotent. Individual resident RGPs have the capacity to produce all excitatory and inhibitory SC neuron types, even at the stage of terminal division. While individual clonal units show no pre-defined cellular composition, the establishment of appropriate relative proportions of distinct neuronal types occurs in a PTEN-dependent manner. Collectively, our findings provide an inaugural framework at the single-RGP/-cell level of the mammalian SC ontogeny.","lang":"eng"}],"oa_version":"Published Version","type":"journal_article","month":"01","page":"230-246.e11","date_created":"2023-04-27T09:41:48Z","file_date_updated":"2024-02-06T13:56:15Z","volume":112},{"date_published":"2023-07-29T00:00:00Z","ddc":["571"],"doi":"10.15479/AT:ISTA:13173","has_accepted_license":"1","oa":1,"citation":{"chicago":"Shigemoto, Ryuichi. “Transition from Tonic to Phasic Neurotransmitter Release by Presynaptic GABAB Receptor Activation in Medial Habenula Terminals.” Institute of Science and Technology Austria, 2023. <a href=\"https://doi.org/10.15479/AT:ISTA:13173\">https://doi.org/10.15479/AT:ISTA:13173</a>.","ieee":"R. Shigemoto, “Transition from tonic to phasic neurotransmitter release by presynaptic GABAB receptor activation in medial habenula terminals.” Institute of Science and Technology Austria, 2023.","short":"R. Shigemoto, (2023).","ama":"Shigemoto R. Transition from tonic to phasic neurotransmitter release by presynaptic GABAB receptor activation in medial habenula terminals. 2023. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:13173\">10.15479/AT:ISTA:13173</a>","apa":"Shigemoto, R. (2023). Transition from tonic to phasic neurotransmitter release by presynaptic GABAB receptor activation in medial habenula terminals. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:13173\">https://doi.org/10.15479/AT:ISTA:13173</a>","mla":"Shigemoto, Ryuichi. <i>Transition from Tonic to Phasic Neurotransmitter Release by Presynaptic GABAB Receptor Activation in Medial Habenula Terminals</i>. Institute of Science and Technology Austria, 2023, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:13173\">10.15479/AT:ISTA:13173</a>.","ista":"Shigemoto R. 2023. Transition from tonic to phasic neurotransmitter release by presynaptic GABAB receptor activation in medial habenula terminals, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:13173\">10.15479/AT:ISTA:13173</a>."},"keyword":["medial habenula","GABAB receptor","vesicle release","Flash and Freeze","Flash and Freeze-fracture"],"status":"public","date_created":"2023-06-29T13:16:42Z","file_date_updated":"2024-02-06T07:21:43Z","title":"Transition from tonic to phasic neurotransmitter release by presynaptic GABAB receptor activation in medial habenula terminals","day":"29","license":"https://creativecommons.org/licenses/by-nc/4.0/","abstract":[{"text":"GABAB receptor (GBR) activation inhibits neurotransmitter release in axon terminals in the brain, except in medial habenula (MHb) terminals, which show robust potentiation. However, mechanisms underlying this enigmatic potentiation remain elusive. Here, we report that GBR activation on MHb terminals induces an activity-dependent transition from a facilitating, tonic to a depressing, phasic neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked synaptic vesicles at the presynaptic active zone (AZ). Strikingly, tonic and phasic release exhibit distinct coupling distances and are selectively affected by deletion of synaptoporin (SPO) and Ca2+-dependent activator protein for secretion 2 (CAPS2), respectively. SPO modulates augmentation, the short-term plasticity associated with tonic release, and CAPS2 retains the increased RRP for initial responses in phasic response trains. Double pre-embedding immunolabeling confirmed the co-localization of CAPS2 and SPO inside the same terminal. The cytosolic protein CAPS2 showed a synaptic vesicle (SV)-associated distribution similar to the vesicular transmembrane protein SPO. A newly developed “Flash and Freeze-fracture” method revealed the release of SPO-associated vesicles in both tonic and phasic modes and activity-dependent recruitment of CAPS2 to the AZ during phasic release, which lasted several minutes. Overall, these results indicate that GBR activation translocates CAPS2 to the AZ along with the fusion of CAPS2-associated SVs, contributing to a persistent RRP increase. Thus, we discovered structural and molecular mechanisms underlying tonic and phasic neurotransmitter release and their transition by GBR activation in MHb terminals.","lang":"eng"}],"date_updated":"2024-02-21T12:19:26Z","file":[{"date_created":"2023-06-29T13:11:22Z","access_level":"closed","title":"Outdated Version","file_id":"13174","date_updated":"2023-11-17T14:30:44Z","checksum":"ed59170869ba621f89f7c1894092192f","description":"After review an updated version of the data is provided","file_size":542873672,"content_type":"application/x-zip-compressed","relation":"main_file","creator":"shigemot","file_name":"Raw data for Koppensteiner et al.zip"},{"creator":"patrickd","file_size":915079,"content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","relation":"main_file","file_name":"11-17-23 Updated Koppensteiner et al. raw data.xlsx","success":1,"access_level":"open_access","date_created":"2023-11-17T14:13:02Z","checksum":"c07860eb82b4d367245f1b589fe5c250","file_id":"14550","date_updated":"2023-11-17T14:13:02Z"},{"access_level":"open_access","date_created":"2024-02-06T07:21:43Z","checksum":"abf84b1699edac4349dc3a92d466fb7b","date_updated":"2024-02-06T07:21:43Z","file_id":"14942","creator":"dernst","content_type":"application/x-zip-compressed","relation":"main_file","file_size":544868924,"success":1,"file_name":"EM_Images.zip"}],"type":"research_data","oa_version":"Published Version","month":"07","author":[{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","first_name":"Ryuichi"}],"article_processing_charge":"No","tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","short":"CC BY-NC (4.0)","image":"/images/cc_by_nc.png","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode"},"_id":"13173","department":[{"_id":"RySh"}],"year":"2023","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Institute of Science and Technology Austria"},{"publication_identifier":{"eissn":["1529-2401"],"issn":["0270-6474"]},"quality_controlled":"1","doi":"10.1523/JNEUROSCI.1514-22.2023","project":[{"grant_number":"793482","_id":"2659CC84-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Ultrastructural analysis of phosphoinositides in nerve terminals: distribution, dynamics and physiological roles in synaptic transmission"},{"grant_number":"694539","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","call_identifier":"H2020","_id":"25CA28EA-B435-11E9-9278-68D0E5697425"}],"issue":"23","language":[{"iso":"eng"}],"isi":1,"day":"07","file":[{"access_level":"open_access","date_created":"2023-07-10T09:04:58Z","checksum":"70b2141870e0bf1c94fd343e18fdbc32","date_updated":"2023-07-10T09:04:58Z","file_id":"13205","creator":"alisjak","content_type":"application/pdf","relation":"main_file","file_size":7794425,"success":1,"file_name":"2023_JN_Eguchi.pdf"}],"author":[{"orcid":"0000-0002-6170-2546","id":"2B7846DC-F248-11E8-B48F-1D18A9856A87","full_name":"Eguchi, Kohgaku","first_name":"Kohgaku","last_name":"Eguchi"},{"id":"3B59276A-F248-11E8-B48F-1D18A9856A87","full_name":"Le Monnier, Elodie","last_name":"Le Monnier","first_name":"Elodie"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","first_name":"Ryuichi"}],"title":"Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar neurons","department":[{"_id":"RySh"}],"pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Society for Neuroscience","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","article_processing_charge":"No","ec_funded":1,"scopus_import":"1","publication":"The Journal of Neuroscience","has_accepted_license":"1","publication_status":"published","oa":1,"acknowledged_ssus":[{"_id":"EM-Fac"}],"ddc":["570"],"date_published":"2023-06-07T00:00:00Z","external_id":{"isi":["001020132100005"],"pmid":["37160366"]},"status":"public","citation":{"short":"K. Eguchi, E. Le Monnier, R. Shigemoto, The Journal of Neuroscience 43 (2023) 4197–4216.","ieee":"K. Eguchi, E. Le Monnier, and R. Shigemoto, “Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar neurons,” <i>The Journal of Neuroscience</i>, vol. 43, no. 23. Society for Neuroscience, pp. 4197–4216, 2023.","chicago":"Eguchi, Kohgaku, Elodie Le Monnier, and Ryuichi Shigemoto. “Nanoscale Phosphoinositide Distribution on Cell Membranes of Mouse Cerebellar Neurons.” <i>The Journal of Neuroscience</i>. Society for Neuroscience, 2023. <a href=\"https://doi.org/10.1523/JNEUROSCI.1514-22.2023\">https://doi.org/10.1523/JNEUROSCI.1514-22.2023</a>.","mla":"Eguchi, Kohgaku, et al. “Nanoscale Phosphoinositide Distribution on Cell Membranes of Mouse Cerebellar Neurons.” <i>The Journal of Neuroscience</i>, vol. 43, no. 23, Society for Neuroscience, 2023, pp. 4197–216, doi:<a href=\"https://doi.org/10.1523/JNEUROSCI.1514-22.2023\">10.1523/JNEUROSCI.1514-22.2023</a>.","ista":"Eguchi K, Le Monnier E, Shigemoto R. 2023. Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar neurons. The Journal of Neuroscience. 43(23), 4197–4216.","apa":"Eguchi, K., Le Monnier, E., &#38; Shigemoto, R. (2023). Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar neurons. <i>The Journal of Neuroscience</i>. Society for Neuroscience. <a href=\"https://doi.org/10.1523/JNEUROSCI.1514-22.2023\">https://doi.org/10.1523/JNEUROSCI.1514-22.2023</a>","ama":"Eguchi K, Le Monnier E, Shigemoto R. Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar neurons. <i>The Journal of Neuroscience</i>. 2023;43(23):4197-4216. doi:<a href=\"https://doi.org/10.1523/JNEUROSCI.1514-22.2023\">10.1523/JNEUROSCI.1514-22.2023</a>"},"intvolume":"        43","type":"journal_article","oa_version":"Published Version","month":"06","date_updated":"2023-10-18T07:12:47Z","abstract":[{"lang":"eng","text":"Phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) plays an essential role in neuronal activities through interaction with various proteins involved in signaling at membranes. However, the distribution pattern of PI(4,5)P2 and the association with these proteins on the neuronal cell membranes remain elusive. In this study, we established a method for visualizing PI(4,5)P2 by SDS-digested freeze-fracture replica labeling (SDS-FRL) to investigate the quantitative nanoscale distribution of PI(4,5)P2 in cryo-fixed brain. We demonstrate that PI(4,5)P2 forms tiny clusters with a mean size of ∼1000 nm2 rather than randomly distributed in cerebellar neuronal membranes in male C57BL/6J mice. These clusters show preferential accumulation in specific membrane compartments of different cell types, in particular, in Purkinje cell (PC) spines and granule cell (GC) presynaptic active zones. Furthermore, we revealed extensive association of PI(4,5)P2 with CaV2.1 and GIRK3 across different membrane compartments, whereas its association with mGluR1α was compartment specific. These results suggest that our SDS-FRL method provides valuable insights into the physiological functions of PI(4,5)P2 in neurons."}],"page":"4197-4216","date_created":"2023-07-09T22:01:12Z","file_date_updated":"2023-07-10T09:04:58Z","volume":43,"year":"2023","acknowledgement":"This work was supported by The Institute of Science and Technology (IST) Austria, the European Union's Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie Grant Agreement No. 793482 (to K.E.) and by the European Research Council (ERC) Grant Agreement No. 694539 (to R.S.). We thank Nicoleta Condruz (IST Austria, Klosterneuburg, Austria) for technical assistance with sample preparation, the Electron Microscopy Facility of IST Austria (Klosterneuburg, Austria) for technical support with EM works, Natalia Baranova (University of Vienna, Vienna, Austria) and Martin Loose (IST Austria, Klosterneuburg, Austria) for advice on liposome preparation, and Yugo Fukazawa (University of Fukui, Fukui, Japan) for comments.","_id":"13202"},{"article_number":"5231","title":"Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA signaling","author":[{"full_name":"Vierra, Nicholas C.","first_name":"Nicholas C.","last_name":"Vierra"},{"full_name":"Ribeiro-Silva, Luisa","last_name":"Ribeiro-Silva","first_name":"Luisa"},{"first_name":"Michael","last_name":"Kirmiz","full_name":"Kirmiz, Michael"},{"full_name":"Van Der List, Deborah","last_name":"Van Der List","first_name":"Deborah"},{"full_name":"Bhandari, Pradeep","id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0863-4481","last_name":"Bhandari","first_name":"Pradeep"},{"full_name":"Mack, Olivia A.","first_name":"Olivia A.","last_name":"Mack"},{"last_name":"Carroll","first_name":"James","full_name":"Carroll, James"},{"last_name":"Le Monnier","first_name":"Elodie","id":"3B59276A-F248-11E8-B48F-1D18A9856A87","full_name":"Le Monnier, Elodie"},{"full_name":"Aicher, Sue A.","last_name":"Aicher","first_name":"Sue A."},{"first_name":"Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi"},{"full_name":"Trimmer, James S.","first_name":"James S.","last_name":"Trimmer"}],"day":"26","file":[{"success":1,"file_name":"2023_NatureComm_Vierra.pdf","creator":"dernst","content_type":"application/pdf","relation":"main_file","file_size":9412549,"checksum":"6ab8aab4e957f626a09a1c73db3388fb","date_updated":"2023-09-06T06:50:07Z","file_id":"14270","access_level":"open_access","date_created":"2023-09-06T06:50:07Z"}],"publication":"Nature Communications","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_processing_charge":"Yes","scopus_import":"1","publisher":"Springer Nature","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"RySh"}],"pmid":1,"doi":"10.1038/s41467-023-40930-6","quality_controlled":"1","publication_identifier":{"eissn":["2041-1723"]},"language":[{"iso":"eng"}],"volume":14,"file_date_updated":"2023-09-06T06:50:07Z","date_created":"2023-09-03T22:01:14Z","month":"08","type":"journal_article","oa_version":"Published Version","abstract":[{"text":"Junctions between the endoplasmic reticulum (ER) and the plasma membrane (PM) are specialized membrane contacts ubiquitous in eukaryotic cells. Concentration of intracellular signaling machinery near ER-PM junctions allows these domains to serve critical roles in lipid and Ca2+ signaling and homeostasis. Subcellular compartmentalization of protein kinase A (PKA) signaling also regulates essential cellular functions, however, no specific association between PKA and ER-PM junctional domains is known. Here, we show that in brain neurons type I PKA is directed to Kv2.1 channel-dependent ER-PM junctional domains via SPHKAP, a type I PKA-specific anchoring protein. SPHKAP association with type I PKA regulatory subunit RI and ER-resident VAP proteins results in the concentration of type I PKA between stacked ER cisternae associated with ER-PM junctions. This ER-associated PKA signalosome enables reciprocal regulation between PKA and Ca2+ signaling machinery to support Ca2+ influx and excitation-transcription coupling. These data reveal that neuronal ER-PM junctions support a receptor-independent form of PKA signaling driven by membrane depolarization and intracellular Ca2+, allowing conversion of information encoded in electrical signals into biochemical changes universally recognized throughout the cell.","lang":"eng"}],"date_updated":"2023-09-06T06:53:32Z","_id":"14253","acknowledgement":"We thank Kayla Templeton and Peter Turcanu for technical assistance, Michelle Salemi for assistance with LC-MS data acquisition and analysis, Dr. Belvin Gong for advice on monoclonal antibody generation, Drs. Maria Casas Prat and Eamonn Dickson for assistance with super-resolution TIRF microscopy, Dr. Oscar Cerda for assistance with the design of TAT-FFAT peptides, Dr. Fernando Santana for helpful discussions, and Dr. Jodi Nunnari for a careful reading of our manuscript. We also thank Dr. Alan Howe, Dr. Sohum Mehta, and Dr. Jin Zhang for providing plasmids used in this study. This project was funded by NIH Grants R01NS114210 and R21NS101648 (J.S.T.), and F32NS108519 (N.C.V.).","year":"2023","date_published":"2023-08-26T00:00:00Z","ddc":["570"],"publication_status":"published","oa":1,"has_accepted_license":"1","intvolume":"        14","citation":{"ama":"Vierra NC, Ribeiro-Silva L, Kirmiz M, et al. Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA signaling. <i>Nature Communications</i>. 2023;14. doi:<a href=\"https://doi.org/10.1038/s41467-023-40930-6\">10.1038/s41467-023-40930-6</a>","mla":"Vierra, Nicholas C., et al. “Neuronal ER-Plasma Membrane Junctions Couple Excitation to Ca2+-Activated PKA Signaling.” <i>Nature Communications</i>, vol. 14, 5231, Springer Nature, 2023, doi:<a href=\"https://doi.org/10.1038/s41467-023-40930-6\">10.1038/s41467-023-40930-6</a>.","ista":"Vierra NC, Ribeiro-Silva L, Kirmiz M, Van Der List D, Bhandari P, Mack OA, Carroll J, Le Monnier E, Aicher SA, Shigemoto R, Trimmer JS. 2023. Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA signaling. Nature Communications. 14, 5231.","apa":"Vierra, N. C., Ribeiro-Silva, L., Kirmiz, M., Van Der List, D., Bhandari, P., Mack, O. A., … Trimmer, J. S. (2023). Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA signaling. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-023-40930-6\">https://doi.org/10.1038/s41467-023-40930-6</a>","ieee":"N. C. Vierra <i>et al.</i>, “Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA signaling,” <i>Nature Communications</i>, vol. 14. Springer Nature, 2023.","chicago":"Vierra, Nicholas C., Luisa Ribeiro-Silva, Michael Kirmiz, Deborah Van Der List, Pradeep Bhandari, Olivia A. Mack, James Carroll, et al. “Neuronal ER-Plasma Membrane Junctions Couple Excitation to Ca2+-Activated PKA Signaling.” <i>Nature Communications</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41467-023-40930-6\">https://doi.org/10.1038/s41467-023-40930-6</a>.","short":"N.C. Vierra, L. Ribeiro-Silva, M. Kirmiz, D. Van Der List, P. Bhandari, O.A. Mack, J. Carroll, E. Le Monnier, S.A. Aicher, R. Shigemoto, J.S. Trimmer, Nature Communications 14 (2023)."},"external_id":{"pmid":["37633939"]},"status":"public"},{"title":"Electron microscopic visualization of single molecules by tag-mediated metal particle labeling","author":[{"last_name":"Shigemoto","first_name":"Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi"}],"day":"01","publication":"Microscopy","article_type":"original","article_processing_charge":"No","scopus_import":"1","ec_funded":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"Oxford Academic","department":[{"_id":"RySh"}],"pmid":1,"doi":"10.1093/jmicro/dfab048","quality_controlled":"1","publication_identifier":{"issn":["2050-5698"],"eissn":["2050-5701"]},"isi":1,"issue":"Supplement_1","language":[{"iso":"eng"}],"project":[{"_id":"25CA28EA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","grant_number":"694539"}],"volume":71,"date_created":"2022-03-20T23:01:39Z","page":"i72-i80","month":"03","type":"journal_article","oa_version":"Published Version","abstract":[{"lang":"eng","text":"Genetically encoded tags have introduced extensive lines of application from purification of tagged proteins to their visualization at the single molecular, cellular, histological and whole-body levels. Combined with other rapidly developing technologies such as clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system, proteomics, super-resolution microscopy and proximity labeling, a large variety of genetically encoded tags have been developed in the last two decades. In this review, I focus on the current status of tag development for electron microscopic (EM) visualization of proteins with metal particle labeling. Compared with conventional immunoelectron microscopy using gold particles, tag-mediated metal particle labeling has several advantages that could potentially improve the sensitivity, spatial and temporal resolution, and applicability to a wide range of proteins of interest (POIs). It may enable researchers to detect single molecules in situ, allowing the quantitative measurement of absolute numbers and exact localization patterns of POI in the ultrastructural context. Thus, genetically encoded tags for EM could revolutionize the field as green fluorescence protein did for light microscopy, although we still have many challenges to overcome before reaching this goal."}],"date_updated":"2023-08-03T06:08:01Z","_id":"10889","acknowledgement":"European Research Council Advanced Grant (694539 to R.S.).","year":"2022","date_published":"2022-03-01T00:00:00Z","main_file_link":[{"url":"https://doi.org/10.1093/jmicro/dfab048","open_access":"1"}],"publication_status":"published","oa":1,"intvolume":"        71","citation":{"short":"R. Shigemoto, Microscopy 71 (2022) i72–i80.","ieee":"R. Shigemoto, “Electron microscopic visualization of single molecules by tag-mediated metal particle labeling,” <i>Microscopy</i>, vol. 71, no. Supplement_1. Oxford Academic, pp. i72–i80, 2022.","chicago":"Shigemoto, Ryuichi. “Electron Microscopic Visualization of Single Molecules by Tag-Mediated Metal Particle Labeling.” <i>Microscopy</i>. Oxford Academic, 2022. <a href=\"https://doi.org/10.1093/jmicro/dfab048\">https://doi.org/10.1093/jmicro/dfab048</a>.","mla":"Shigemoto, Ryuichi. “Electron Microscopic Visualization of Single Molecules by Tag-Mediated Metal Particle Labeling.” <i>Microscopy</i>, vol. 71, no. Supplement_1, Oxford Academic, 2022, pp. i72–80, doi:<a href=\"https://doi.org/10.1093/jmicro/dfab048\">10.1093/jmicro/dfab048</a>.","ista":"Shigemoto R. 2022. Electron microscopic visualization of single molecules by tag-mediated metal particle labeling. Microscopy. 71(Supplement_1), i72–i80.","apa":"Shigemoto, R. (2022). Electron microscopic visualization of single molecules by tag-mediated metal particle labeling. <i>Microscopy</i>. Oxford Academic. <a href=\"https://doi.org/10.1093/jmicro/dfab048\">https://doi.org/10.1093/jmicro/dfab048</a>","ama":"Shigemoto R. Electron microscopic visualization of single molecules by tag-mediated metal particle labeling. <i>Microscopy</i>. 2022;71(Supplement_1):i72-i80. doi:<a href=\"https://doi.org/10.1093/jmicro/dfab048\">10.1093/jmicro/dfab048</a>"},"external_id":{"pmid":["35275179"],"isi":["000768384100011"]},"status":"public"},{"isi":1,"language":[{"iso":"eng"}],"project":[{"call_identifier":"H2020","_id":"25CA28EA-B435-11E9-9278-68D0E5697425","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","grant_number":"694539"},{"name":"LGI1 antibody-induced pathophysiology in synapses","_id":"05970B30-7A3F-11EA-A408-12923DDC885E","grant_number":"I04638"}],"doi":"10.3389/fnana.2022.846615","quality_controlled":"1","publication_identifier":{"eissn":["16625129"]},"publication":"Frontiers in Neuroanatomy","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"scopus_import":"1","article_processing_charge":"No","ec_funded":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"Frontiers","department":[{"_id":"RySh"}],"pmid":1,"article_number":"846615","title":"The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals","author":[{"last_name":"Eguchi","first_name":"Kohgaku","orcid":"0000-0002-6170-2546","id":"2B7846DC-F248-11E8-B48F-1D18A9856A87","full_name":"Eguchi, Kohgaku"},{"last_name":"Montanaro-Punzengruber","first_name":"Jacqueline-Claire","id":"3786AB44-F248-11E8-B48F-1D18A9856A87","full_name":"Montanaro-Punzengruber, Jacqueline-Claire"},{"first_name":"Elodie","last_name":"Le Monnier","full_name":"Le Monnier, Elodie","id":"3B59276A-F248-11E8-B48F-1D18A9856A87"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","first_name":"Ryuichi"}],"file":[{"checksum":"51ec9b90e7da919e22c01a15489eaacd","date_updated":"2022-03-21T09:41:19Z","file_id":"10911","access_level":"open_access","date_created":"2022-03-21T09:41:19Z","success":1,"file_name":"2022_FrontiersNeuroanatomy_Eguchi.pdf","creator":"dernst","relation":"main_file","content_type":"application/pdf","file_size":2416395}],"day":"24","intvolume":"        16","citation":{"apa":"Eguchi, K., Montanaro-Punzengruber, J.-C., Le Monnier, E., &#38; Shigemoto, R. (2022). The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals. <i>Frontiers in Neuroanatomy</i>. Frontiers. <a href=\"https://doi.org/10.3389/fnana.2022.846615\">https://doi.org/10.3389/fnana.2022.846615</a>","ista":"Eguchi K, Montanaro-Punzengruber J-C, Le Monnier E, Shigemoto R. 2022. The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals. Frontiers in Neuroanatomy. 16, 846615.","mla":"Eguchi, Kohgaku, et al. “The Number and Distinct Clustering Patterns of Voltage-Gated Calcium Channels in Nerve Terminals.” <i>Frontiers in Neuroanatomy</i>, vol. 16, 846615, Frontiers, 2022, doi:<a href=\"https://doi.org/10.3389/fnana.2022.846615\">10.3389/fnana.2022.846615</a>.","ama":"Eguchi K, Montanaro-Punzengruber J-C, Le Monnier E, Shigemoto R. The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals. <i>Frontiers in Neuroanatomy</i>. 2022;16. doi:<a href=\"https://doi.org/10.3389/fnana.2022.846615\">10.3389/fnana.2022.846615</a>","short":"K. Eguchi, J.-C. Montanaro-Punzengruber, E. Le Monnier, R. Shigemoto, Frontiers in Neuroanatomy 16 (2022).","chicago":"Eguchi, Kohgaku, Jacqueline-Claire Montanaro-Punzengruber, Elodie Le Monnier, and Ryuichi Shigemoto. “The Number and Distinct Clustering Patterns of Voltage-Gated Calcium Channels in Nerve Terminals.” <i>Frontiers in Neuroanatomy</i>. Frontiers, 2022. <a href=\"https://doi.org/10.3389/fnana.2022.846615\">https://doi.org/10.3389/fnana.2022.846615</a>.","ieee":"K. Eguchi, J.-C. Montanaro-Punzengruber, E. Le Monnier, and R. Shigemoto, “The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals,” <i>Frontiers in Neuroanatomy</i>, vol. 16. Frontiers, 2022."},"status":"public","external_id":{"pmid":["35280978"],"isi":["000766662700001"]},"date_published":"2022-02-24T00:00:00Z","ddc":["570"],"oa":1,"publication_status":"published","has_accepted_license":"1","_id":"10890","acknowledgement":"This work was supported by the European Research Council advanced grant No. 694539 and the joint German-Austrian DFG and FWF project SYNABS (FWF: I-4638-B) to RS.\r\nThe authors thank Walter Kaufmann for his critical comments on the manuscript.","year":"2022","volume":16,"date_created":"2022-03-20T23:01:39Z","file_date_updated":"2022-03-21T09:41:19Z","type":"journal_article","oa_version":"Published Version","month":"02","abstract":[{"text":"Upon the arrival of action potentials at nerve terminals, neurotransmitters are released from synaptic vesicles (SVs) by exocytosis. CaV2.1, 2.2, and 2.3 are the major subunits of the voltage-gated calcium channel (VGCC) responsible for increasing intraterminal calcium levels and triggering SV exocytosis in the central nervous system (CNS) synapses. The two-dimensional analysis of CaV2 distributions using sodium dodecyl sulfate (SDS)-digested freeze-fracture replica labeling (SDS-FRL) has revealed their numbers, densities, and nanoscale clustering patterns in individual presynaptic active zones. The variation in these properties affects the coupling of VGCCs with calcium sensors on SVs, synaptic efficacy, and temporal precision of transmission. In this study, we summarize how the morphological parameters of CaV2 distribution obtained using SDS-FRL differ depending on the different types of synapses and could correspond to functional properties in synaptic transmission.","lang":"eng"}],"date_updated":"2024-10-29T07:57:26Z"},{"file_date_updated":"2023-01-27T07:53:18Z","date_created":"2023-01-16T09:45:51Z","volume":14,"date_updated":"2023-08-04T09:23:10Z","abstract":[{"lang":"eng","text":"Alzheimer’s disease (AD) is characterized by a reorganization of brain activity determining network hyperexcitability and loss of synaptic plasticity. Precisely, a dysfunction in metabotropic GABAB receptor signalling through G protein-gated inwardly rectifying K+ (GIRK or Kir3) channels on the hippocampus has been postulated. Thus, we determined the impact of amyloid-β (Aβ) pathology in GIRK channel density, subcellular distribution, and its association with GABAB receptors in hippocampal CA1 pyramidal neurons from the APP/PS1 mouse model using quantitative SDS-digested freeze-fracture replica labelling (SDS-FRL) and proximity ligation in situ assay (P-LISA). In wild type mice, single SDS-FRL detection revealed a similar dendritic gradient for GIRK1 and GIRK2 in CA1 pyramidal cells, with higher densities in spines, and GIRK3 showed a lower and uniform distribution. Double SDS-FRL showed a co-clustering of GIRK2 and GIRK1 in post- and presynaptic compartments, but not for GIRK2 and GIRK3. Likewise, double GABAB1 and GIRK2 SDS-FRL detection displayed a high degree of co-clustering in nanodomains (40–50 nm) mostly in spines and axon terminals. In APP/PS1 mice, the density of GIRK2 and GIRK1, but not for GIRK3, was significantly reduced along the neuronal surface of CA1 pyramidal cells and in axon terminals contacting them. Importantly, GABAB1 and GIRK2 co-clustering was not present in APP/PS1 mice. Similarly, P-LISA experiments revealed a significant reduction in GABAB1 and GIRK2 interaction on the hippocampus of this animal model. Overall, our results provide compelling evidence showing a significant reduction on the cell surface density of pre- and postsynaptic GIRK1 and GIRK2, but not GIRK3, and a decline in GABAB receptors and GIRK2 channels co-clustering in hippocampal pyramidal neurons from APP/PS1 mice, thus suggesting that a disruption in the GABAB receptor–GIRK channel membrane assembly causes dysregulation in the GABAB signalling via GIRK channels in this AD animal model."}],"month":"09","type":"journal_article","oa_version":"Published Version","_id":"12212","year":"2022","acknowledgement":"We thank Ms. Diane Latawiec for the English revision of the manuscript. Funding sources were the Spanish Ministerio de Economía y Competitividad, Junta de Comunidades de Castilla-La Mancha (Spain), and Life Science Innovation Center at University of Fukui. We thank Centres de Recerca de Catalunya (CERCA) Programme/Generalitat de Catalunya for IDIBELL institutional support. We thank Hitoshi Takagi and Takako Maegawa at the University of Fukui for their technical assistance on SDS-FRL experiments.\r\nThis work was supported by grants from the Spanish Ministerio de Economía y Competitividad (BFU2015-63769-R, RTI2018-095812-B-I00, and PID2021-125875OB-I00) and Junta de Comunidades de Castilla-La Mancha (SBPLY/17/180501/000229 and SBPLY/21/180501/000064) to RL, Life Science Innovation Center at University of Fukui and JSPS KAKENHI (Grant Numbers 16H04662, 19H03323, and 20H05058) to YF, and Margarita Salas fellowship from Ministerio de Universidades and Universidad de Castilla-La Mancha to AMB.","ddc":["570"],"date_published":"2022-09-21T00:00:00Z","has_accepted_license":"1","publication_status":"published","oa":1,"citation":{"ama":"Martín-Belmonte A, Aguado C, Alfaro-Ruiz R, et al. Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice. <i>Alzheimer’s Research &#38; Therapy</i>. 2022;14. doi:<a href=\"https://doi.org/10.1186/s13195-022-01078-5\">10.1186/s13195-022-01078-5</a>","apa":"Martín-Belmonte, A., Aguado, C., Alfaro-Ruiz, R., Moreno-Martínez, A. E., de la Ossa, L., Aso, E., … Luján, R. (2022). Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice. <i>Alzheimer’s Research &#38; Therapy</i>. Springer Nature. <a href=\"https://doi.org/10.1186/s13195-022-01078-5\">https://doi.org/10.1186/s13195-022-01078-5</a>","mla":"Martín-Belmonte, Alejandro, et al. “Nanoscale Alterations in GABAB Receptors and GIRK Channel Organization on the Hippocampus of APP/PS1 Mice.” <i>Alzheimer’s Research &#38; Therapy</i>, vol. 14, 136, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1186/s13195-022-01078-5\">10.1186/s13195-022-01078-5</a>.","ista":"Martín-Belmonte A, Aguado C, Alfaro-Ruiz R, Moreno-Martínez AE, de la Ossa L, Aso E, Gómez-Acero L, Shigemoto R, Fukazawa Y, Ciruela F, Luján R. 2022. Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice. Alzheimer’s Research &#38; Therapy. 14, 136.","chicago":"Martín-Belmonte, Alejandro, Carolina Aguado, Rocío Alfaro-Ruiz, Ana Esther Moreno-Martínez, Luis de la Ossa, Ester Aso, Laura Gómez-Acero, et al. “Nanoscale Alterations in GABAB Receptors and GIRK Channel Organization on the Hippocampus of APP/PS1 Mice.” <i>Alzheimer’s Research &#38; Therapy</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1186/s13195-022-01078-5\">https://doi.org/10.1186/s13195-022-01078-5</a>.","ieee":"A. Martín-Belmonte <i>et al.</i>, “Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice,” <i>Alzheimer’s Research &#38; Therapy</i>, vol. 14. Springer Nature, 2022.","short":"A. Martín-Belmonte, C. Aguado, R. Alfaro-Ruiz, A.E. Moreno-Martínez, L. de la Ossa, E. Aso, L. Gómez-Acero, R. Shigemoto, Y. Fukazawa, F. Ciruela, R. Luján, Alzheimer’s Research &#38; Therapy 14 (2022)."},"intvolume":"        14","external_id":{"isi":["000857985500001"]},"status":"public","title":"Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice","article_number":"136","day":"21","file":[{"access_level":"open_access","date_created":"2023-01-27T07:53:18Z","checksum":"88e49715ad6a1abf0fdb27efd65368dc","file_id":"12413","date_updated":"2023-01-27T07:53:18Z","creator":"dernst","file_size":11013325,"content_type":"application/pdf","relation":"main_file","file_name":"2022_AlzheimersResearch_MartinBelmont.pdf","success":1}],"author":[{"full_name":"Martín-Belmonte, Alejandro","first_name":"Alejandro","last_name":"Martín-Belmonte"},{"full_name":"Aguado, Carolina","first_name":"Carolina","last_name":"Aguado"},{"full_name":"Alfaro-Ruiz, Rocío","last_name":"Alfaro-Ruiz","first_name":"Rocío"},{"first_name":"Ana Esther","last_name":"Moreno-Martínez","full_name":"Moreno-Martínez, Ana Esther"},{"first_name":"Luis","last_name":"de la Ossa","full_name":"de la Ossa, Luis"},{"full_name":"Aso, Ester","last_name":"Aso","first_name":"Ester"},{"first_name":"Laura","last_name":"Gómez-Acero","full_name":"Gómez-Acero, Laura"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","first_name":"Ryuichi"},{"first_name":"Yugo","last_name":"Fukazawa","full_name":"Fukazawa, Yugo"},{"full_name":"Ciruela, Francisco","last_name":"Ciruela","first_name":"Francisco"},{"full_name":"Luján, Rafael","first_name":"Rafael","last_name":"Luján"}],"article_processing_charge":"No","scopus_import":"1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","publication":"Alzheimer's Research & Therapy","department":[{"_id":"RySh"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"Springer Nature","quality_controlled":"1","doi":"10.1186/s13195-022-01078-5","publication_identifier":{"issn":["1758-9193"]},"language":[{"iso":"eng"}],"isi":1,"keyword":["Cognitive Neuroscience","Neurology (clinical)","Neurology"]},{"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"article_type":"original","ec_funded":1,"article_processing_charge":"No","publication":"Current Biology","department":[{"_id":"MaJö"},{"_id":"RySh"}],"publisher":"Elsevier","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","title":"Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation","day":"11","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","file":[{"checksum":"b7b9c8bc84a08befce365c675229a7d1","file_id":"8678","date_updated":"2020-10-19T13:31:28Z","access_level":"open_access","date_created":"2020-10-19T13:31:28Z","file_name":"2021_CurrentBiology_Fredes.pdf","success":1,"creator":"dernst","file_size":4915964,"content_type":"application/pdf","relation":"main_file"}],"author":[{"full_name":"Fredes Tolorza, Felipe A","id":"384825DA-F248-11E8-B48F-1D18A9856A87","last_name":"Fredes Tolorza","first_name":"Felipe A"},{"id":"371B3D6E-F248-11E8-B48F-1D18A9856A87","full_name":"Silva Sifuentes, Maria A","first_name":"Maria A","last_name":"Silva Sifuentes"},{"id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","full_name":"Koppensteiner, Peter","last_name":"Koppensteiner","first_name":"Peter"},{"first_name":"Kenta","last_name":"Kobayashi","full_name":"Kobayashi, Kenta"},{"first_name":"Maximilian A","last_name":"Jösch","full_name":"Jösch, Maximilian A","orcid":"0000-0002-3937-1330","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Shigemoto","first_name":"Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi"}],"issue":"1","language":[{"iso":"eng"}],"isi":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"}],"quality_controlled":"1","doi":"10.1016/j.cub.2020.09.074","_id":"7551","year":"2021","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.","file_date_updated":"2020-10-19T13:31:28Z","date_created":"2020-02-28T10:56:18Z","volume":31,"month":"01","type":"journal_article","oa_version":"Published Version","date_updated":"2023-08-04T10:47:11Z","abstract":[{"lang":"eng","text":"Novelty facilitates formation of memories. The detection of novelty and storage of contextual memories are both mediated by the hippocampus, yet the mechanisms that link these two functions remain to be defined. Dentate granule cells (GCs) of the dorsal hippocampus fire upon novelty exposure forming engrams of contextual memory. However, their key excitatory inputs from the entorhinal cortex are not responsive to novelty and are insufficient to make dorsal GCs fire reliably. Here we uncover a powerful glutamatergic pathway to dorsal GCs from ventral hippocampal mossy cells (MCs) that relays novelty, and is necessary and sufficient for driving dorsal GCs activation. Furthermore, manipulation of ventral MCs activity bidirectionally regulates novelty-induced contextual memory acquisition. Our results show that ventral MCs activity controls memory formation through an intra-hippocampal interaction mechanism gated by novelty."}],"page":"P25-38.E5","citation":{"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.","ieee":"F. A. Fredes Tolorza, M. A. Silva Sifuentes, P. Koppensteiner, K. Kobayashi, M. A. Jösch, and R. Shigemoto, “Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation,” <i>Current Biology</i>, vol. 31, no. 1. Elsevier, p. P25–38.E5, 2021.","chicago":"Fredes Tolorza, Felipe A, Maria A Silva Sifuentes, Peter Koppensteiner, Kenta Kobayashi, Maximilian A Jösch, and Ryuichi Shigemoto. “Ventro-Dorsal Hippocampal Pathway Gates Novelty-Induced Contextual Memory Formation.” <i>Current Biology</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.cub.2020.09.074\">https://doi.org/10.1016/j.cub.2020.09.074</a>.","mla":"Fredes Tolorza, Felipe A., et al. “Ventro-Dorsal Hippocampal Pathway Gates Novelty-Induced Contextual Memory Formation.” <i>Current Biology</i>, vol. 31, no. 1, Elsevier, 2021, p. P25–38.E5, doi:<a href=\"https://doi.org/10.1016/j.cub.2020.09.074\">10.1016/j.cub.2020.09.074</a>.","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.","apa":"Fredes Tolorza, F. A., Silva Sifuentes, M. A., Koppensteiner, P., Kobayashi, K., Jösch, M. A., &#38; Shigemoto, R. (2021). Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation. <i>Current Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cub.2020.09.074\">https://doi.org/10.1016/j.cub.2020.09.074</a>","ama":"Fredes Tolorza FA, Silva Sifuentes MA, Koppensteiner P, Kobayashi K, Jösch MA, Shigemoto R. Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation. <i>Current Biology</i>. 2021;31(1):P25-38.E5. doi:<a href=\"https://doi.org/10.1016/j.cub.2020.09.074\">10.1016/j.cub.2020.09.074</a>"},"intvolume":"        31","related_material":{"link":[{"relation":"press_release","description":"News on IST Homepage","url":"https://ist.ac.at/en/news/remembering-novelty/"}]},"external_id":{"isi":["000614361000020"]},"status":"public","date_published":"2021-01-11T00:00:00Z","ddc":["570"],"has_accepted_license":"1","oa":1,"publication_status":"published"},{"project":[{"grant_number":"694539","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","call_identifier":"H2020","_id":"25CA28EA-B435-11E9-9278-68D0E5697425"}],"issue":"14","language":[{"iso":"eng"}],"isi":1,"publication_identifier":{"eissn":["1091-6490"]},"quality_controlled":"1","doi":"10.1073/pnas.1920827118","department":[{"_id":"EM-Fac"},{"_id":"RySh"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"National Academy of Sciences","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","article_processing_charge":"No","ec_funded":1,"scopus_import":"1","publication":"PNAS","day":"06","file":[{"date_updated":"2021-04-19T10:10:56Z","file_id":"9340","checksum":"dd014f68ae9d7d8d8fc4139a24e04506","date_created":"2021-04-19T10:10:56Z","access_level":"open_access","success":1,"file_name":"2021_PNAS_Schoepf.pdf","relation":"main_file","content_type":"application/pdf","file_size":2603911,"creator":"dernst"}],"author":[{"full_name":"Schöpf, Clemens L.","last_name":"Schöpf","first_name":"Clemens L."},{"full_name":"Ablinger, Cornelia","last_name":"Ablinger","first_name":"Cornelia"},{"full_name":"Geisler, Stefanie M.","first_name":"Stefanie M.","last_name":"Geisler"},{"full_name":"Stanika, Ruslan I.","last_name":"Stanika","first_name":"Ruslan I."},{"full_name":"Campiglio, Marta","first_name":"Marta","last_name":"Campiglio"},{"full_name":"Kaufmann, Walter","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9735-5315","last_name":"Kaufmann","first_name":"Walter"},{"full_name":"Nimmervoll, Benedikt","last_name":"Nimmervoll","first_name":"Benedikt"},{"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","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi"},{"full_name":"Obermair, Gerald J.","first_name":"Gerald J.","last_name":"Obermair"}],"title":"Presynaptic α2δ subunits are key organizers of glutamatergic synapses","status":"public","external_id":{"isi":["000637398300002"]},"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).","ieee":"C. L. Schöpf <i>et al.</i>, “Presynaptic α2δ subunits are key organizers of glutamatergic synapses,” <i>PNAS</i>, vol. 118, no. 14. National Academy of Sciences, 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.” <i>PNAS</i>. National Academy of Sciences, 2021. <a href=\"https://doi.org/10.1073/pnas.1920827118\">https://doi.org/10.1073/pnas.1920827118</a>.","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).","mla":"Schöpf, Clemens L., et al. “Presynaptic Α2δ Subunits Are Key Organizers of Glutamatergic Synapses.” <i>PNAS</i>, vol. 118, no. 14, National Academy of Sciences, 2021, doi:<a href=\"https://doi.org/10.1073/pnas.1920827118\">10.1073/pnas.1920827118</a>.","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. <i>PNAS</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.1920827118\">https://doi.org/10.1073/pnas.1920827118</a>","ama":"Schöpf CL, Ablinger C, Geisler SM, et al. Presynaptic α2δ subunits are key organizers of glutamatergic synapses. <i>PNAS</i>. 2021;118(14). doi:<a href=\"https://doi.org/10.1073/pnas.1920827118\">10.1073/pnas.1920827118</a>"},"intvolume":"       118","has_accepted_license":"1","publication_status":"published","oa":1,"acknowledged_ssus":[{"_id":"EM-Fac"}],"ddc":["570"],"date_published":"2021-04-06T00:00:00Z","year":"2021","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.","_id":"9330","oa_version":"Published Version","type":"journal_article","month":"04","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"}],"date_updated":"2023-08-08T13:08:47Z","file_date_updated":"2021-04-19T10:10:56Z","date_created":"2021-04-18T22:01:40Z","volume":118},{"citation":{"chicago":"Bhandari, Pradeep, David H Vandael, Diego Fernández-Fernández, Thorsten Fritzius, David Kleindienst, Hüseyin C Önal, Jacqueline-Claire Montanaro-Punzengruber, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from Medial Habenula Terminals.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/ELIFE.68274\">https://doi.org/10.7554/ELIFE.68274</a>.","ieee":"P. Bhandari <i>et al.</i>, “GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","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).","ama":"Bhandari P, Vandael DH, Fernández-Fernández D, et al. GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/ELIFE.68274\">10.7554/ELIFE.68274</a>","apa":"Bhandari, P., Vandael, D. H., Fernández-Fernández, D., Fritzius, T., Kleindienst, D., Önal, H. C., … Koppensteiner, P. (2021). GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/ELIFE.68274\">https://doi.org/10.7554/ELIFE.68274</a>","mla":"Bhandari, Pradeep, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from Medial Habenula Terminals.” <i>ELife</i>, vol. 10, e68274, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/ELIFE.68274\">10.7554/ELIFE.68274</a>.","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."},"related_material":{"link":[{"url":"https://doi.org/10.1101/2020.04.16.045112","relation":"earlier_version"}],"record":[{"id":"9562","status":"public","relation":"dissertation_contains"}]},"intvolume":"        10","external_id":{"isi":["000651761700001"]},"status":"public","ddc":["570"],"date_published":"2021-04-29T00:00:00Z","has_accepted_license":"1","publication_status":"published","oa":1,"_id":"9437","year":"2021","acknowledgement":"We are grateful to Akari Hagiwara and Toshihisa Ohtsuka for CAST antibody, and Masahiko Watanabe for neurexin antibody. We thank David Adams for kindly providing the stable Cav2.3 cell line. Cav2.3 KO mice were kindly provided by Tsutomu Tanabe. This project has received funding from the European Research Council (ERC) and European Commission (EC), under the European Union’s Horizon 2020 research and innovation programme (ERC grant agreement no. 694539 to Ryuichi Shigemoto, no. 692692 to Peter Jonas, and the Marie Skłodowska-Curie grant agreement no. 665385 to Cihan Önal), the Swiss National Science Foundation Grant 31003A-172881 to Bernhard Bettler and Deutsche Forschungsgemeinschaft (For 2143) and BIOSS-2 to Akos Kulik.","date_created":"2021-05-30T22:01:23Z","file_date_updated":"2021-05-31T09:43:09Z","volume":10,"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"}],"date_updated":"2024-03-25T23:30:16Z","type":"journal_article","oa_version":"Published Version","month":"04","language":[{"iso":"eng"}],"isi":1,"project":[{"name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","_id":"25CA28EA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"694539"},{"grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse"},{"name":"International IST Doctoral Program","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385"}],"quality_controlled":"1","doi":"10.7554/ELIFE.68274","publication_identifier":{"eissn":["2050-084X"]},"ec_funded":1,"scopus_import":"1","article_processing_charge":"No","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","publication":"eLife","department":[{"_id":"RySh"},{"_id":"PeJo"}],"publisher":"eLife Sciences Publications","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","title":"GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals","article_number":"e68274","day":"29","file":[{"success":1,"file_name":"2021_eLife_Bhandari.pdf","relation":"main_file","content_type":"application/pdf","file_size":8174719,"creator":"cziletti","date_updated":"2021-05-31T09:43:09Z","file_id":"9440","checksum":"6ebcb79999f889766f7cd79ee134ad28","date_created":"2021-05-31T09:43:09Z","access_level":"open_access"}],"author":[{"full_name":"Bhandari, Pradeep","orcid":"0000-0003-0863-4481","id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","last_name":"Bhandari","first_name":"Pradeep"},{"last_name":"Vandael","first_name":"David H","full_name":"Vandael, David H","orcid":"0000-0001-7577-1676","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Diego","last_name":"Fernández-Fernández","full_name":"Fernández-Fernández, Diego"},{"full_name":"Fritzius, Thorsten","first_name":"Thorsten","last_name":"Fritzius"},{"first_name":"David","last_name":"Kleindienst","id":"42E121A4-F248-11E8-B48F-1D18A9856A87","full_name":"Kleindienst, David"},{"first_name":"Hüseyin C","last_name":"Önal","full_name":"Önal, Hüseyin C","id":"4659D740-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2771-2011"},{"full_name":"Montanaro-Punzengruber, Jacqueline-Claire","id":"3786AB44-F248-11E8-B48F-1D18A9856A87","last_name":"Montanaro-Punzengruber","first_name":"Jacqueline-Claire"},{"full_name":"Gassmann, Martin","first_name":"Martin","last_name":"Gassmann"},{"last_name":"Jonas","first_name":"Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M"},{"first_name":"Akos","last_name":"Kulik","full_name":"Kulik, Akos"},{"full_name":"Bettler, Bernhard","first_name":"Bernhard","last_name":"Bettler"},{"full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi","last_name":"Shigemoto"},{"orcid":"0000-0002-3509-1948","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","full_name":"Koppensteiner, Peter","last_name":"Koppensteiner","first_name":"Peter"}]},{"department":[{"_id":"RySh"}],"pmid":1,"publisher":"Elsevier","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"article_type":"original","ec_funded":1,"article_processing_charge":"No","scopus_import":"1","publication":"Neurobiology of Learning and Memory","file":[{"file_name":"2021_NeurobLearnMemory_Fredes.pdf","success":1,"file_size":1994793,"relation":"main_file","content_type":"application/pdf","creator":"cziletti","file_id":"9694","date_updated":"2021-07-19T13:46:06Z","checksum":"8e8298a9e8c7df146ad23f32c2a63929","date_created":"2021-07-19T13:46:06Z","access_level":"open_access"}],"day":"30","author":[{"full_name":"Fredes, Felipe","first_name":"Felipe","last_name":"Fredes"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","first_name":"Ryuichi"}],"article_number":"107486","title":"The role of hippocampal mossy cells in novelty detection","project":[{"grant_number":"694539","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","_id":"25CA28EA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"language":[{"iso":"eng"}],"isi":1,"publication_identifier":{"eissn":["10959564"],"issn":["10747427"]},"quality_controlled":"1","doi":"10.1016/j.nlm.2021.107486","year":"2021","acknowledgement":"This work was supported by a European Research Council Advanced Grant 694539 to Ryuichi Shigemoto.","_id":"9641","type":"journal_article","month":"06","oa_version":"Published Version","date_updated":"2023-08-10T14:10:37Z","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"}],"date_created":"2021-07-11T22:01:16Z","file_date_updated":"2021-07-19T13:46:06Z","volume":183,"status":"public","external_id":{"pmid":["34214666"],"isi":["000677694900004"]},"citation":{"short":"F. Fredes, R. Shigemoto, Neurobiology of Learning and Memory 183 (2021).","chicago":"Fredes, Felipe, and Ryuichi Shigemoto. “The Role of Hippocampal Mossy Cells in Novelty Detection.” <i>Neurobiology of Learning and Memory</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.nlm.2021.107486\">https://doi.org/10.1016/j.nlm.2021.107486</a>.","ieee":"F. Fredes and R. Shigemoto, “The role of hippocampal mossy cells in novelty detection,” <i>Neurobiology of Learning and Memory</i>, vol. 183. Elsevier, 2021.","apa":"Fredes, F., &#38; Shigemoto, R. (2021). The role of hippocampal mossy cells in novelty detection. <i>Neurobiology of Learning and Memory</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.nlm.2021.107486\">https://doi.org/10.1016/j.nlm.2021.107486</a>","mla":"Fredes, Felipe, and Ryuichi Shigemoto. “The Role of Hippocampal Mossy Cells in Novelty Detection.” <i>Neurobiology of Learning and Memory</i>, vol. 183, 107486, Elsevier, 2021, doi:<a href=\"https://doi.org/10.1016/j.nlm.2021.107486\">10.1016/j.nlm.2021.107486</a>.","ista":"Fredes F, Shigemoto R. 2021. The role of hippocampal mossy cells in novelty detection. Neurobiology of Learning and Memory. 183, 107486.","ama":"Fredes F, Shigemoto R. The role of hippocampal mossy cells in novelty detection. <i>Neurobiology of Learning and Memory</i>. 2021;183. doi:<a href=\"https://doi.org/10.1016/j.nlm.2021.107486\">10.1016/j.nlm.2021.107486</a>"},"intvolume":"       183","has_accepted_license":"1","oa":1,"publication_status":"published","ddc":["610"],"date_published":"2021-06-30T00:00:00Z"},{"_id":"10051","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.","year":"2021","volume":41,"date_created":"2021-09-27T14:33:13Z","file_date_updated":"2022-05-31T09:10:15Z","page":"7742-7767","date_updated":"2023-08-14T06:56:30Z","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."}],"oa_version":"Published Version","type":"journal_article","month":"09","intvolume":"        41","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.","chicago":"Butola, Tanvi, Theocharis Alvanos, Anika Hintze, Peter Koppensteiner, David Kleindienst, Ryuichi Shigemoto, Carolin Wichmann, and Tobias Moser. “RIM-Binding Protein 2 Organizes Ca<sup>21</sup> Channel Topography and Regulates Release Probability and Vesicle Replenishment at a Fast Central Synapse.” <i>Journal of Neuroscience</i>. Society for Neuroscience, 2021. <a href=\"https://doi.org/10.1523/JNEUROSCI.0586-21.2021\">https://doi.org/10.1523/JNEUROSCI.0586-21.2021</a>.","ieee":"T. Butola <i>et al.</i>, “RIM-binding protein 2 organizes Ca<sup>21</sup> channel topography and regulates release probability and vesicle replenishment at a fast central synapse,” <i>Journal of Neuroscience</i>, vol. 41, no. 37. Society for Neuroscience, pp. 7742–7767, 2021.","apa":"Butola, T., Alvanos, T., Hintze, A., Koppensteiner, P., Kleindienst, D., Shigemoto, R., … Moser, T. (2021). RIM-binding protein 2 organizes Ca<sup>21</sup> channel topography and regulates release probability and vesicle replenishment at a fast central synapse. <i>Journal of Neuroscience</i>. Society for Neuroscience. <a href=\"https://doi.org/10.1523/JNEUROSCI.0586-21.2021\">https://doi.org/10.1523/JNEUROSCI.0586-21.2021</a>","mla":"Butola, Tanvi, et al. “RIM-Binding Protein 2 Organizes Ca<sup>21</sup> Channel Topography and Regulates Release Probability and Vesicle Replenishment at a Fast Central Synapse.” <i>Journal of Neuroscience</i>, vol. 41, no. 37, Society for Neuroscience, 2021, pp. 7742–67, doi:<a href=\"https://doi.org/10.1523/JNEUROSCI.0586-21.2021\">10.1523/JNEUROSCI.0586-21.2021</a>.","ista":"Butola T, Alvanos T, Hintze A, Koppensteiner P, Kleindienst D, Shigemoto R, Wichmann C, Moser T. 2021. RIM-binding protein 2 organizes Ca<sup>21</sup> channel topography and regulates release probability and vesicle replenishment at a fast central synapse. Journal of Neuroscience. 41(37), 7742–7767.","ama":"Butola T, Alvanos T, Hintze A, et al. RIM-binding protein 2 organizes Ca<sup>21</sup> channel topography and regulates release probability and vesicle replenishment at a fast central synapse. <i>Journal of Neuroscience</i>. 2021;41(37):7742-7767. doi:<a href=\"https://doi.org/10.1523/JNEUROSCI.0586-21.2021\">10.1523/JNEUROSCI.0586-21.2021</a>"},"external_id":{"pmid":["34353898"],"isi":["000752287700005"]},"status":"public","date_published":"2021-09-15T00:00:00Z","ddc":["570"],"publication_status":"published","oa":1,"has_accepted_license":"1","publication":"Journal of Neuroscience","scopus_import":"1","article_processing_charge":"No","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"Society for Neuroscience","pmid":1,"department":[{"_id":"RySh"}],"title":"RIM-binding protein 2 organizes Ca<sup>21</sup> channel topography and regulates release probability and vesicle replenishment at a fast central synapse","author":[{"last_name":"Butola","first_name":"Tanvi","full_name":"Butola, Tanvi"},{"full_name":"Alvanos, Theocharis","first_name":"Theocharis","last_name":"Alvanos"},{"last_name":"Hintze","first_name":"Anika","full_name":"Hintze, Anika"},{"full_name":"Koppensteiner, Peter","orcid":"0000-0002-3509-1948","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","first_name":"Peter","last_name":"Koppensteiner"},{"full_name":"Kleindienst, David","id":"42E121A4-F248-11E8-B48F-1D18A9856A87","last_name":"Kleindienst","first_name":"David"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","first_name":"Ryuichi"},{"last_name":"Wichmann","first_name":"Carolin","full_name":"Wichmann, Carolin"},{"last_name":"Moser","first_name":"Tobias","full_name":"Moser, Tobias"}],"day":"15","file":[{"file_name":"2021_JourNeuroscience_Butola.pdf","success":1,"creator":"dernst","file_size":11571961,"content_type":"application/pdf","relation":"main_file","checksum":"769ab627c7355a50ccfd445e43a5f351","file_id":"11423","date_updated":"2022-05-31T09:10:15Z","access_level":"open_access","date_created":"2022-05-31T09:10:15Z"}],"isi":1,"language":[{"iso":"eng"}],"issue":"37","doi":"10.1523/JNEUROSCI.0586-21.2021","quality_controlled":"1","publication_identifier":{"eissn":["1529-2401"],"issn":["0270-6474"]}},{"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"eLife Sciences Publications","department":[{"_id":"RySh"}],"publication":"eLife","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","scopus_import":"1","article_processing_charge":"No","author":[{"full_name":"Biane, Celia","last_name":"Biane","first_name":"Celia"},{"full_name":"Rückerl, Florian","last_name":"Rückerl","first_name":"Florian"},{"full_name":"Abrahamsson, Therese","last_name":"Abrahamsson","first_name":"Therese"},{"first_name":"Cécile","last_name":"Saint-Cloment","full_name":"Saint-Cloment, Cécile"},{"full_name":"Mariani, Jean","last_name":"Mariani","first_name":"Jean"},{"orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","first_name":"Ryuichi"},{"first_name":"David A.","last_name":"Digregorio","full_name":"Digregorio, David A."},{"last_name":"Sherrard","first_name":"Rachel M.","full_name":"Sherrard, Rachel M."},{"last_name":"Cathala","first_name":"Laurence","full_name":"Cathala, Laurence"}],"day":"03","file":[{"date_updated":"2021-12-10T08:31:41Z","file_id":"10528","checksum":"c7c33c3319428d56e332e22349c50ed3","date_created":"2021-12-10T08:31:41Z","access_level":"open_access","success":1,"file_name":"2021_eLife_Biane.pdf","content_type":"application/pdf","relation":"main_file","file_size":13131322,"creator":"cchlebak"}],"article_number":"e65954","title":"Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons","isi":1,"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["2050-084X"]},"doi":"10.7554/eLife.65954","quality_controlled":"1","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","_id":"10403","month":"11","type":"journal_article","oa_version":"Published Version","abstract":[{"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.","lang":"eng"}],"date_updated":"2023-08-14T13:12:07Z","volume":10,"file_date_updated":"2021-12-10T08:31:41Z","date_created":"2021-12-05T23:01:40Z","external_id":{"isi":["000715789500001"]},"status":"public","intvolume":"        10","citation":{"ama":"Biane C, Rückerl F, Abrahamsson T, et al. Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/eLife.65954\">10.7554/eLife.65954</a>","mla":"Biane, Celia, et al. “Developmental Emergence of Two-Stage Nonlinear Synaptic Integration in Cerebellar Interneurons.” <i>ELife</i>, vol. 10, e65954, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/eLife.65954\">10.7554/eLife.65954</a>.","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. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.65954\">https://doi.org/10.7554/eLife.65954</a>","ieee":"C. Biane <i>et al.</i>, “Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","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.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/eLife.65954\">https://doi.org/10.7554/eLife.65954</a>.","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)."},"publication_status":"published","oa":1,"has_accepted_license":"1","ddc":["570"],"date_published":"2021-11-03T00:00:00Z"},{"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."}],"date_updated":"2024-03-25T23:30:16Z","type":"book_chapter","oa_version":"None","month":"07","page":"267-283","date_created":"2021-07-30T09:34:56Z","volume":169,"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.).","_id":"9756","has_accepted_license":"1","publication_status":"published","date_published":"2021-07-27T00:00:00Z","ddc":["573"],"status":"public","alternative_title":["Neuromethods"],"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: <i> Receptor and Ion Channel Detection in the Brain</i>. Vol 169. Neuromethods. New York: Humana; 2021:267-283. doi:<a href=\"https://doi.org/10.1007/978-1-0716-1522-5_19\">10.1007/978-1-0716-1522-5_19</a>","apa":"Kaufmann, W., Kleindienst, D., Harada, H., &#38; Shigemoto, R. (2021). High-Resolution localization and quantitation of membrane proteins by SDS-digested freeze-fracture replica labeling (SDS-FRL). In <i> Receptor and Ion Channel Detection in the Brain</i> (Vol. 169, pp. 267–283). New York: Humana. <a href=\"https://doi.org/10.1007/978-1-0716-1522-5_19\">https://doi.org/10.1007/978-1-0716-1522-5_19</a>","mla":"Kaufmann, Walter, et al. “High-Resolution Localization and Quantitation of Membrane Proteins by SDS-Digested Freeze-Fracture Replica Labeling (SDS-FRL).” <i> Receptor and Ion Channel Detection in the Brain</i>, vol. 169, Humana, 2021, pp. 267–83, doi:<a href=\"https://doi.org/10.1007/978-1-0716-1522-5_19\">10.1007/978-1-0716-1522-5_19</a>.","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.","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 <i> Receptor and Ion Channel Detection in the Brain</i>, 169:267–83. Neuromethods. New York: Humana, 2021. <a href=\"https://doi.org/10.1007/978-1-0716-1522-5_19\">https://doi.org/10.1007/978-1-0716-1522-5_19</a>.","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 <i> Receptor and Ion Channel Detection in the Brain</i>, vol. 169, New York: Humana, 2021, pp. 267–283.","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."},"intvolume":"       169","related_material":{"record":[{"relation":"dissertation_contains","id":"9562","status":"public"}]},"day":"27","author":[{"first_name":"Walter","last_name":"Kaufmann","full_name":"Kaufmann, Walter","orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87"},{"first_name":"David","last_name":"Kleindienst","full_name":"Kleindienst, David","id":"42E121A4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Harada, Harumi","orcid":"0000-0001-7429-7896","id":"2E55CDF2-F248-11E8-B48F-1D18A9856A87","last_name":"Harada","first_name":"Harumi"},{"last_name":"Shigemoto","first_name":"Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi"}],"title":"High-Resolution localization and quantitation of membrane proteins by SDS-digested freeze-fracture replica labeling (SDS-FRL)","place":"New York","department":[{"_id":"RySh"},{"_id":"EM-Fac"}],"publisher":"Humana","user_id":"D865714E-FA4E-11E9-B85B-F5C5E5697425","article_processing_charge":"No","ec_funded":1,"publication":" Receptor and Ion Channel Detection in the Brain","publication_identifier":{"eisbn":["9781071615225"],"isbn":["9781071615218"]},"quality_controlled":"1","doi":"10.1007/978-1-0716-1522-5_19","project":[{"grant_number":"694539","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","call_identifier":"H2020","_id":"25CA28EA-B435-11E9-9278-68D0E5697425"},{"grant_number":"720270","_id":"25CBA828-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Human Brain Project Specific Grant Agreement 1 (HBP SGA 1)"}],"language":[{"iso":"eng"}],"series_title":"Neuromethods","keyword":["Freeze-fracture replica: Deep learning","Immunogold labeling","Integral membrane protein","Electron microscopy"]},{"intvolume":"         9","citation":{"apa":"Bao, J., Graupner, M., Astorga, G., Collin, T., Jalil, A., Indriati, D. W., … Llano, I. (2020). Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.56839\">https://doi.org/10.7554/eLife.56839</a>","ista":"Bao J, Graupner M, Astorga G, Collin T, Jalil A, Indriati DW, Bradley J, Shigemoto R, Llano I. 2020. Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo. eLife. 9, e56839.","mla":"Bao, Jin, et al. “Synergism of Type 1 Metabotropic and Ionotropic Glutamate Receptors in Cerebellar Molecular Layer Interneurons in Vivo.” <i>ELife</i>, vol. 9, e56839, eLife Sciences Publications, 2020, doi:<a href=\"https://doi.org/10.7554/eLife.56839\">10.7554/eLife.56839</a>.","ama":"Bao J, Graupner M, Astorga G, et al. Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo. <i>eLife</i>. 2020;9. doi:<a href=\"https://doi.org/10.7554/eLife.56839\">10.7554/eLife.56839</a>","short":"J. Bao, M. Graupner, G. Astorga, T. Collin, A. Jalil, D.W. Indriati, J. Bradley, R. Shigemoto, I. Llano, ELife 9 (2020).","chicago":"Bao, Jin, Michael Graupner, Guadalupe Astorga, Thibault Collin, Abdelali Jalil, Dwi Wahyu Indriati, Jonathan Bradley, Ryuichi Shigemoto, and Isabel Llano. “Synergism of Type 1 Metabotropic and Ionotropic Glutamate Receptors in Cerebellar Molecular Layer Interneurons in Vivo.” <i>ELife</i>. eLife Sciences Publications, 2020. <a href=\"https://doi.org/10.7554/eLife.56839\">https://doi.org/10.7554/eLife.56839</a>.","ieee":"J. Bao <i>et al.</i>, “Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo,” <i>eLife</i>, vol. 9. eLife Sciences Publications, 2020."},"status":"public","external_id":{"pmid":["32401196"],"isi":["000535191600001"]},"ddc":["570"],"date_published":"2020-05-13T00:00:00Z","publication_status":"published","oa":1,"has_accepted_license":"1","_id":"7878","year":"2020","volume":9,"date_created":"2020-05-24T22:00:58Z","file_date_updated":"2020-07-14T12:48:04Z","date_updated":"2023-08-21T06:26:50Z","abstract":[{"lang":"eng","text":"Type 1 metabotropic glutamate receptors (mGluR1s) are key elements in neuronal signaling. While their function is well documented in slices, requirements for their activation in vivo are poorly understood. We examine this question in adult mice in vivo using 2-photon imaging of cerebellar molecular layer interneurons (MLIs) expressing GCaMP. In anesthetized mice, parallel fiber activation evokes beam-like Cai rises in postsynaptic MLIs which depend on co-activation of mGluR1s and ionotropic glutamate receptors (iGluRs). In awake mice, blocking mGluR1 decreases Cai rises associated with locomotion. In vitro studies and freeze-fracture electron microscopy show that the iGluR-mGluR1 interaction is synergistic and favored by close association of the two classes of receptors. Altogether our results suggest that mGluR1s, acting in synergy with iGluRs, potently contribute to processing cerebellar neuronal signaling under physiological conditions."}],"oa_version":"Published Version","month":"05","type":"journal_article","isi":1,"language":[{"iso":"eng"}],"doi":"10.7554/eLife.56839","quality_controlled":"1","publication_identifier":{"eissn":["2050084X"]},"publication":"eLife","scopus_import":"1","article_processing_charge":"No","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"publisher":"eLife Sciences Publications","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","pmid":1,"department":[{"_id":"RySh"}],"title":"Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo","article_number":"e56839","author":[{"full_name":"Bao, Jin","last_name":"Bao","first_name":"Jin"},{"first_name":"Michael","last_name":"Graupner","full_name":"Graupner, Michael"},{"full_name":"Astorga, Guadalupe","last_name":"Astorga","first_name":"Guadalupe"},{"last_name":"Collin","first_name":"Thibault","full_name":"Collin, Thibault"},{"first_name":"Abdelali","last_name":"Jalil","full_name":"Jalil, Abdelali"},{"last_name":"Indriati","first_name":"Dwi Wahyu","full_name":"Indriati, Dwi Wahyu"},{"full_name":"Bradley, Jonathan","last_name":"Bradley","first_name":"Jonathan"},{"full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","last_name":"Shigemoto","first_name":"Ryuichi"},{"full_name":"Llano, Isabel","first_name":"Isabel","last_name":"Llano"}],"day":"13","file":[{"file_name":"2020_eLife_Bao.pdf","creator":"dernst","file_size":4832050,"relation":"main_file","content_type":"application/pdf","checksum":"8ea99bb6660cc407dbdb00c173b01683","file_id":"7891","date_updated":"2020-07-14T12:48:04Z","access_level":"open_access","date_created":"2020-05-26T09:34:54Z"}]},{"title":"Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses","article_number":"6737","day":"14","file":[{"success":1,"file_name":"2020_JournMolecSciences_Kleindienst.pdf","content_type":"application/pdf","relation":"main_file","file_size":5748456,"creator":"dernst","date_updated":"2020-09-21T14:08:58Z","file_id":"8551","checksum":"2e4f62f3cfe945b7391fc3070e5a289f","date_created":"2020-09-21T14:08:58Z","access_level":"open_access"}],"author":[{"id":"42E121A4-F248-11E8-B48F-1D18A9856A87","full_name":"Kleindienst, David","first_name":"David","last_name":"Kleindienst"},{"last_name":"Montanaro-Punzengruber","first_name":"Jacqueline-Claire","id":"3786AB44-F248-11E8-B48F-1D18A9856A87","full_name":"Montanaro-Punzengruber, Jacqueline-Claire"},{"full_name":"Bhandari, Pradeep","id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0863-4481","first_name":"Pradeep","last_name":"Bhandari"},{"full_name":"Case, Matthew J","id":"44B7CA5A-F248-11E8-B48F-1D18A9856A87","first_name":"Matthew J","last_name":"Case"},{"last_name":"Fukazawa","first_name":"Yugo","full_name":"Fukazawa, Yugo"},{"orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","last_name":"Shigemoto"}],"ec_funded":1,"article_processing_charge":"No","scopus_import":"1","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"publication":"International Journal of Molecular Sciences","department":[{"_id":"RySh"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"MDPI","quality_controlled":"1","doi":"10.3390/ijms21186737","publication_identifier":{"eissn":["14220067"],"issn":["16616596"]},"language":[{"iso":"eng"}],"issue":"18","isi":1,"project":[{"grant_number":"694539","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","_id":"25CA28EA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"name":"Mechanism of formation and maintenance of input side-dependent asymmetry in the hippocampus","_id":"25D32BC0-B435-11E9-9278-68D0E5697425"},{"name":"Human Brain Project Specific Grant Agreement 2 (HBP SGA 2)","call_identifier":"H2020","_id":"26436750-B435-11E9-9278-68D0E5697425","grant_number":"785907"}],"date_created":"2020-09-20T22:01:35Z","file_date_updated":"2020-09-21T14:08:58Z","volume":21,"date_updated":"2024-03-25T23:30:16Z","abstract":[{"text":"The molecular anatomy of synapses defines their characteristics in transmission and plasticity. Precise measurements of the number and distribution of synaptic proteins are important for our understanding of synapse heterogeneity within and between brain regions. Freeze–fracture replica immunogold electron microscopy enables us to analyze them quantitatively on a two-dimensional membrane surface. Here, we introduce Darea software, which utilizes deep learning for analysis of replica images and demonstrate its usefulness for quick measurements of the pre- and postsynaptic areas, density and distribution of gold particles at synapses in a reproducible manner. We used Darea for comparing glutamate receptor and calcium channel distributions between hippocampal CA3-CA1 spine synapses on apical and basal dendrites, which differ in signaling pathways involved in synaptic plasticity. We found that apical synapses express a higher density of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and a stronger increase of AMPA receptors with synaptic size, while basal synapses show a larger increase in N-methyl-D-aspartate (NMDA) receptors with size. Interestingly, AMPA and NMDA receptors are segregated within postsynaptic sites and negatively correlated in density among both apical and basal synapses. In the presynaptic sites, Cav2.1 voltage-gated calcium channels show similar densities in apical and basal synapses with distributions consistent with an exclusion zone model of calcium channel-release site topography.","lang":"eng"}],"type":"journal_article","oa_version":"Published Version","month":"09","_id":"8532","year":"2020","acknowledgement":"This research was funded by Austrian Academy of Sciences, DOC fellowship to D.K., European Research\r\nCouncil Advanced Grant 694539 and European Union Human Brain Project (HBP) SGA2 785907 to R.S.\r\nWe acknowledge Elena Hollergschwandtner for technical support.","date_published":"2020-09-14T00:00:00Z","ddc":["570"],"has_accepted_license":"1","publication_status":"published","oa":1,"citation":{"chicago":"Kleindienst, David, Jacqueline-Claire Montanaro-Punzengruber, Pradeep Bhandari, Matthew J Case, Yugo Fukazawa, and Ryuichi Shigemoto. “Deep Learning-Assisted High-Throughput Analysis of Freeze-Fracture Replica Images Applied to Glutamate Receptors and Calcium Channels at Hippocampal Synapses.” <i>International Journal of Molecular Sciences</i>. MDPI, 2020. <a href=\"https://doi.org/10.3390/ijms21186737\">https://doi.org/10.3390/ijms21186737</a>.","ieee":"D. Kleindienst, J.-C. Montanaro-Punzengruber, P. Bhandari, M. J. Case, Y. Fukazawa, and R. Shigemoto, “Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses,” <i>International Journal of Molecular Sciences</i>, vol. 21, no. 18. MDPI, 2020.","short":"D. Kleindienst, J.-C. Montanaro-Punzengruber, P. Bhandari, M.J. Case, Y. Fukazawa, R. Shigemoto, International Journal of Molecular Sciences 21 (2020).","ama":"Kleindienst D, Montanaro-Punzengruber J-C, Bhandari P, Case MJ, Fukazawa Y, Shigemoto R. Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses. <i>International Journal of Molecular Sciences</i>. 2020;21(18). doi:<a href=\"https://doi.org/10.3390/ijms21186737\">10.3390/ijms21186737</a>","apa":"Kleindienst, D., Montanaro-Punzengruber, J.-C., Bhandari, P., Case, M. J., Fukazawa, Y., &#38; Shigemoto, R. (2020). Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses. <i>International Journal of Molecular Sciences</i>. MDPI. <a href=\"https://doi.org/10.3390/ijms21186737\">https://doi.org/10.3390/ijms21186737</a>","ista":"Kleindienst D, Montanaro-Punzengruber J-C, Bhandari P, Case MJ, Fukazawa Y, Shigemoto R. 2020. Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses. International Journal of Molecular Sciences. 21(18), 6737.","mla":"Kleindienst, David, et al. “Deep Learning-Assisted High-Throughput Analysis of Freeze-Fracture Replica Images Applied to Glutamate Receptors and Calcium Channels at Hippocampal Synapses.” <i>International Journal of Molecular Sciences</i>, vol. 21, no. 18, 6737, MDPI, 2020, doi:<a href=\"https://doi.org/10.3390/ijms21186737\">10.3390/ijms21186737</a>."},"intvolume":"        21","related_material":{"record":[{"relation":"dissertation_contains","id":"9562","status":"public"}]},"status":"public","external_id":{"isi":["000579945300001"]}},{"external_id":{"isi":["000496410200001"],"pmid":["31625608"]},"status":"public","intvolume":"       528","citation":{"ieee":"C. Nakamoto <i>et al.</i>, “Expression mapping, quantification, and complex formation of GluD1 and GluD2 glutamate receptors in adult mouse brain,” <i>Journal of Comparative Neurology</i>, vol. 528, no. 6. Wiley, pp. 1003–1027, 2020.","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.” <i>Journal of Comparative Neurology</i>. Wiley, 2020. <a href=\"https://doi.org/10.1002/cne.24792\">https://doi.org/10.1002/cne.24792</a>.","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.","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. <i>Journal of Comparative Neurology</i>. 2020;528(6):1003-1027. doi:<a href=\"https://doi.org/10.1002/cne.24792\">10.1002/cne.24792</a>","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.","mla":"Nakamoto, Chihiro, et al. “Expression Mapping, Quantification, and Complex Formation of GluD1 and GluD2 Glutamate Receptors in Adult Mouse Brain.” <i>Journal of Comparative Neurology</i>, vol. 528, no. 6, Wiley, 2020, pp. 1003–27, doi:<a href=\"https://doi.org/10.1002/cne.24792\">10.1002/cne.24792</a>.","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. <i>Journal of Comparative Neurology</i>. Wiley. <a href=\"https://doi.org/10.1002/cne.24792\">https://doi.org/10.1002/cne.24792</a>"},"publication_status":"published","has_accepted_license":"1","ddc":["571","599"],"date_published":"2020-04-01T00:00:00Z","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.","year":"2020","_id":"7148","page":"1003-1027","date_updated":"2023-08-17T14:06:50Z","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"}],"type":"journal_article","oa_version":"None","month":"04","volume":528,"date_created":"2019-12-04T16:09:29Z","isi":1,"language":[{"iso":"eng"}],"issue":"6","publication_identifier":{"eissn":["1096-9861"],"issn":["0021-9967"]},"doi":"10.1002/cne.24792","quality_controlled":"1","publisher":"Wiley","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","pmid":1,"department":[{"_id":"RySh"}],"publication":"Journal of Comparative Neurology","article_processing_charge":"No","scopus_import":"1","article_type":"original","author":[{"full_name":"Nakamoto, Chihiro","first_name":"Chihiro","last_name":"Nakamoto"},{"first_name":"Kohtarou","last_name":"Konno","full_name":"Konno, Kohtarou"},{"full_name":"Miyazaki, Taisuke","first_name":"Taisuke","last_name":"Miyazaki"},{"full_name":"Nakatsukasa, Ena","first_name":"Ena","last_name":"Nakatsukasa"},{"first_name":"Rie","last_name":"Natsume","full_name":"Natsume, Rie"},{"last_name":"Abe","first_name":"Manabu","full_name":"Abe, Manabu"},{"full_name":"Kawamura, Meiko","last_name":"Kawamura","first_name":"Meiko"},{"first_name":"Yugo","last_name":"Fukazawa","full_name":"Fukazawa, Yugo"},{"first_name":"Ryuichi","last_name":"Shigemoto","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi"},{"full_name":"Yamasaki, Miwako","first_name":"Miwako","last_name":"Yamasaki"},{"full_name":"Sakimura, Kenji","first_name":"Kenji","last_name":"Sakimura"},{"last_name":"Watanabe","first_name":"Masahiko","full_name":"Watanabe, Masahiko"}],"day":"01","title":"Expression mapping, quantification, and complex formation of GluD1 and GluD2 glutamate receptors in adult mouse brain"},{"page":"554-575","month":"05","type":"journal_article","oa_version":"Published Version","abstract":[{"text":"The hippocampus plays key roles in learning and memory and is a main target of Alzheimer's disease (AD), which causes progressive memory impairments. Despite numerous investigations about the processes required for the normal hippocampal functions, the neurotransmitter receptors involved in the synaptic deficits by which AD disables the hippocampus are not yet characterized. By combining histoblots, western blots, immunohistochemistry and high‐resolution immunoelectron microscopic methods for GABAB receptors, this study provides a quantitative description of the expression and the subcellular localization of GABAB1 in the hippocampus in a mouse model of AD at 1, 6 and 12 months of age. Western blots and histoblots showed that the total amount of protein and the laminar expression pattern of GABAB1 were similar in APP/PS1 mice and in age‐matched wild‐type mice. In contrast, immunoelectron microscopic techniques showed that the subcellular localization of GABAB1 subunit did not change significantly in APP/PS1 mice at 1 month of age, was significantly reduced in the stratum lacunosum‐moleculare of CA1 pyramidal cells at 6 months of age and significantly reduced at the membrane surface of CA1 pyramidal cells at 12 months of age. This reduction of plasma membrane GABAB1 was paralleled by a significant increase of the subunit at the intracellular sites. We further observed a decrease of membrane‐targeted GABAB receptors in axon terminals contacting CA1 pyramidal cells. Our data demonstrate compartment‐ and age‐dependent reduction of plasma membrane‐targeted GABAB receptors in the CA1 region of the hippocampus, suggesting that this decrease might be enough to alter the GABAB‐mediated synaptic transmission taking place in AD.","lang":"eng"}],"date_updated":"2023-09-06T14:48:01Z","volume":30,"date_created":"2019-12-22T23:00:43Z","file_date_updated":"2020-09-22T09:47:19Z","year":"2020","_id":"7207","oa":1,"publication_status":"published","has_accepted_license":"1","date_published":"2020-05-01T00:00:00Z","ddc":["570"],"status":"public","external_id":{"pmid":["31729777"],"isi":["000502270900001"]},"intvolume":"        30","citation":{"ama":"Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, et al. Reduction in the neuronal surface of post and presynaptic GABA&#62;B&#60; receptors in the hippocampus in a mouse model of Alzheimer’s disease. <i>Brain Pathology</i>. 2020;30(3):554-575. doi:<a href=\"https://doi.org/10.1111/bpa.12802\">10.1111/bpa.12802</a>","mla":"Martín-Belmonte, Alejandro, et al. “Reduction in the Neuronal Surface of Post and Presynaptic GABA&#62;B&#60; Receptors in the Hippocampus in a Mouse Model of Alzheimer’s Disease.” <i>Brain Pathology</i>, vol. 30, no. 3, Wiley, 2020, pp. 554–75, doi:<a href=\"https://doi.org/10.1111/bpa.12802\">10.1111/bpa.12802</a>.","ista":"Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, Moreno-Martínez AE, De La Ossa L, Martínez-Hernández J, Buisson A, Früh S, Bettler B, Shigemoto R, Fukazawa Y, Luján R. 2020. Reduction in the neuronal surface of post and presynaptic GABA&#62;B&#60; receptors in the hippocampus in a mouse model of Alzheimer’s disease. Brain Pathology. 30(3), 554–575.","apa":"Martín-Belmonte, A., Aguado, C., Alfaro-Ruíz, R., Moreno-Martínez, A. E., De La Ossa, L., Martínez-Hernández, J., … Luján, R. (2020). Reduction in the neuronal surface of post and presynaptic GABA&#62;B&#60; receptors in the hippocampus in a mouse model of Alzheimer’s disease. <i>Brain Pathology</i>. Wiley. <a href=\"https://doi.org/10.1111/bpa.12802\">https://doi.org/10.1111/bpa.12802</a>","ieee":"A. Martín-Belmonte <i>et al.</i>, “Reduction in the neuronal surface of post and presynaptic GABA&#62;B&#60; receptors in the hippocampus in a mouse model of Alzheimer’s disease,” <i>Brain Pathology</i>, vol. 30, no. 3. Wiley, pp. 554–575, 2020.","chicago":"Martín-Belmonte, Alejandro, Carolina Aguado, Rocío Alfaro-Ruíz, Ana Esther Moreno-Martínez, Luis De La Ossa, José Martínez-Hernández, Alain Buisson, et al. “Reduction in the Neuronal Surface of Post and Presynaptic GABA&#62;B&#60; Receptors in the Hippocampus in a Mouse Model of Alzheimer’s Disease.” <i>Brain Pathology</i>. Wiley, 2020. <a href=\"https://doi.org/10.1111/bpa.12802\">https://doi.org/10.1111/bpa.12802</a>.","short":"A. Martín-Belmonte, C. Aguado, R. Alfaro-Ruíz, A.E. Moreno-Martínez, L. De La Ossa, J. Martínez-Hernández, A. Buisson, S. Früh, B. Bettler, R. Shigemoto, Y. Fukazawa, R. Luján, Brain Pathology 30 (2020) 554–575."},"author":[{"first_name":"Alejandro","last_name":"Martín-Belmonte","full_name":"Martín-Belmonte, Alejandro"},{"full_name":"Aguado, Carolina","last_name":"Aguado","first_name":"Carolina"},{"last_name":"Alfaro-Ruíz","first_name":"Rocío","full_name":"Alfaro-Ruíz, Rocío"},{"first_name":"Ana Esther","last_name":"Moreno-Martínez","full_name":"Moreno-Martínez, Ana Esther"},{"last_name":"De La Ossa","first_name":"Luis","full_name":"De La Ossa, Luis"},{"last_name":"Martínez-Hernández","first_name":"José","full_name":"Martínez-Hernández, José"},{"full_name":"Buisson, Alain","last_name":"Buisson","first_name":"Alain"},{"full_name":"Früh, Simon","last_name":"Früh","first_name":"Simon"},{"first_name":"Bernhard","last_name":"Bettler","full_name":"Bettler, Bernhard"},{"orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","first_name":"Ryuichi"},{"last_name":"Fukazawa","first_name":"Yugo","full_name":"Fukazawa, Yugo"},{"first_name":"Rafael","last_name":"Luján","full_name":"Luján, Rafael"}],"day":"01","file":[{"date_created":"2020-09-22T09:47:19Z","access_level":"open_access","file_id":"8554","date_updated":"2020-09-22T09:47:19Z","checksum":"549cc1b18f638a21d17a939ba5563fa9","file_size":4220935,"relation":"main_file","content_type":"application/pdf","creator":"dernst","file_name":"2020_BrainPathology_MartinBelmonte.pdf","success":1}],"title":"Reduction in the neuronal surface of post and presynaptic GABA>B< receptors in the hippocampus in a mouse model of Alzheimer's disease","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publisher":"Wiley","department":[{"_id":"RySh"}],"pmid":1,"publication":"Brain Pathology","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","ec_funded":1,"article_processing_charge":"No","scopus_import":"1","publication_identifier":{"issn":["10156305"],"eissn":["17503639"]},"doi":"10.1111/bpa.12802","quality_controlled":"1","project":[{"grant_number":"720270","call_identifier":"H2020","_id":"25CBA828-B435-11E9-9278-68D0E5697425","name":"Human Brain Project Specific Grant Agreement 1 (HBP SGA 1)"},{"name":"Human Brain Project Specific Grant Agreement 2 (HBP SGA 2)","_id":"26436750-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"785907"}],"isi":1,"issue":"3","language":[{"iso":"eng"}]},{"department":[{"_id":"RySh"}],"pmid":1,"publisher":"MDPI","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"scopus_import":"1","article_processing_charge":"No","publication":"International journal of molecular sciences","day":"02","file":[{"file_id":"7669","date_updated":"2020-07-14T12:48:01Z","checksum":"b9d2f1657d8c4a74b01a62b474d009b0","date_created":"2020-04-20T11:43:18Z","access_level":"open_access","file_name":"2020_JournMolecSciences_Martin_Belmonte.pdf","file_size":2941197,"relation":"main_file","content_type":"application/pdf","creator":"dernst"}],"author":[{"full_name":"Martín-Belmonte, Alejandro","first_name":"Alejandro","last_name":"Martín-Belmonte"},{"full_name":"Aguado, Carolina","last_name":"Aguado","first_name":"Carolina"},{"first_name":"Rocío","last_name":"Alfaro-Ruíz","full_name":"Alfaro-Ruíz, Rocío"},{"last_name":"Moreno-Martínez","first_name":"Ana Esther","full_name":"Moreno-Martínez, Ana Esther"},{"last_name":"De La Ossa","first_name":"Luis","full_name":"De La Ossa, Luis"},{"last_name":"Martínez-Hernández","first_name":"José","full_name":"Martínez-Hernández, José"},{"last_name":"Buisson","first_name":"Alain","full_name":"Buisson, Alain"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","last_name":"Shigemoto"},{"first_name":"Yugo","last_name":"Fukazawa","full_name":"Fukazawa, Yugo"},{"last_name":"Luján","first_name":"Rafael","full_name":"Luján, Rafael"}],"article_number":"2459","title":"Density of GABAB receptors is reduced in granule cells of the hippocampus in a mouse model of Alzheimer's disease","issue":"7","language":[{"iso":"eng"}],"isi":1,"publication_identifier":{"eissn":["14220067"]},"quality_controlled":"1","doi":"10.3390/ijms21072459","year":"2020","_id":"7664","type":"journal_article","month":"04","oa_version":"Published Version","date_updated":"2023-08-21T06:13:19Z","abstract":[{"lang":"eng","text":"Metabotropic γ-aminobutyric acid (GABAB) receptors contribute to the control of network activity and information processing in hippocampal circuits by regulating neuronal excitability and synaptic transmission. The dysfunction in the dentate gyrus (DG) has been implicated in Alzheimer´s disease (AD). Given the involvement of GABAB receptors in AD, to determine their subcellular localisation and possible alteration in granule cells of the DG in a mouse model of AD at 12 months of age, we used high-resolution immunoelectron microscopic analysis. Immunohistochemistry at the light microscopic level showed that the regional and cellular expression pattern of GABAB1 was similar in an AD model mouse expressing mutated human amyloid precursor protein and presenilin1 (APP/PS1) and in age-matched wild type mice. High-resolution immunoelectron microscopy revealed a distance-dependent gradient of immunolabelling for GABAB receptors, increasing from proximal to distal dendrites in both wild type and APP/PS1 mice. However, the overall density of GABAB receptors at the neuronal surface of these postsynaptic compartments of granule cells was significantly reduced in APP/PS1 mice. Parallel to this reduction in surface receptors, we found a significant increase in GABAB1 at cytoplasmic sites. GABAB receptors were also detected at presynaptic sites in the molecular layer of the DG. We also found a decrease in plasma membrane GABAB receptors in axon terminals contacting dendritic spines of granule cells, which was more pronounced in the outer than in the inner molecular layer. Altogether, our data showing post- and presynaptic reduction in surface GABAB receptors in the DG suggest the alteration of the GABAB-mediated modulation of excitability and synaptic transmission in granule cells, which may contribute to the cognitive dysfunctions in the APP/PS1 model of AD"}],"file_date_updated":"2020-07-14T12:48:01Z","date_created":"2020-04-19T22:00:55Z","volume":21,"status":"public","external_id":{"isi":["000535574200201"],"pmid":["32252271"]},"citation":{"ama":"Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, et al. Density of GABAB receptors is reduced in granule cells of the hippocampus in a mouse model of Alzheimer’s disease. <i>International journal of molecular sciences</i>. 2020;21(7). doi:<a href=\"https://doi.org/10.3390/ijms21072459\">10.3390/ijms21072459</a>","apa":"Martín-Belmonte, A., Aguado, C., Alfaro-Ruíz, R., Moreno-Martínez, A. E., De La Ossa, L., Martínez-Hernández, J., … Luján, R. (2020). Density of GABAB receptors is reduced in granule cells of the hippocampus in a mouse model of Alzheimer’s disease. <i>International Journal of Molecular Sciences</i>. MDPI. <a href=\"https://doi.org/10.3390/ijms21072459\">https://doi.org/10.3390/ijms21072459</a>","mla":"Martín-Belmonte, Alejandro, et al. “Density of GABAB Receptors Is Reduced in Granule Cells of the Hippocampus in a Mouse Model of Alzheimer’s Disease.” <i>International Journal of Molecular Sciences</i>, vol. 21, no. 7, 2459, MDPI, 2020, doi:<a href=\"https://doi.org/10.3390/ijms21072459\">10.3390/ijms21072459</a>.","ista":"Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, Moreno-Martínez AE, De La Ossa L, Martínez-Hernández J, Buisson A, Shigemoto R, Fukazawa Y, Luján R. 2020. Density of GABAB receptors is reduced in granule cells of the hippocampus in a mouse model of Alzheimer’s disease. International journal of molecular sciences. 21(7), 2459.","chicago":"Martín-Belmonte, Alejandro, Carolina Aguado, Rocío Alfaro-Ruíz, Ana Esther Moreno-Martínez, Luis De La Ossa, José Martínez-Hernández, Alain Buisson, Ryuichi Shigemoto, Yugo Fukazawa, and Rafael Luján. “Density of GABAB Receptors Is Reduced in Granule Cells of the Hippocampus in a Mouse Model of Alzheimer’s Disease.” <i>International Journal of Molecular Sciences</i>. MDPI, 2020. <a href=\"https://doi.org/10.3390/ijms21072459\">https://doi.org/10.3390/ijms21072459</a>.","ieee":"A. Martín-Belmonte <i>et al.</i>, “Density of GABAB receptors is reduced in granule cells of the hippocampus in a mouse model of Alzheimer’s disease,” <i>International journal of molecular sciences</i>, vol. 21, no. 7. MDPI, 2020.","short":"A. Martín-Belmonte, C. Aguado, R. Alfaro-Ruíz, A.E. Moreno-Martínez, L. De La Ossa, J. Martínez-Hernández, A. Buisson, R. Shigemoto, Y. Fukazawa, R. Luján, International Journal of Molecular Sciences 21 (2020)."},"intvolume":"        21","has_accepted_license":"1","oa":1,"publication_status":"published","ddc":["570"],"date_published":"2020-04-02T00:00:00Z"}]