[{"author":[{"last_name":"Miki","first_name":"Takafumi","full_name":"Miki, Takafumi"},{"full_name":"Kaufmann, Walter","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","last_name":"Kaufmann","orcid":"0000-0001-9735-5315","first_name":"Walter"},{"full_name":"Malagon, Gerardo","last_name":"Malagon","first_name":"Gerardo"},{"first_name":"Laura","last_name":"Gomez","full_name":"Gomez, Laura"},{"full_name":"Tabuchi, Katsuhiko","last_name":"Tabuchi","first_name":"Katsuhiko"},{"last_name":"Watanabe","first_name":"Masahiko","full_name":"Watanabe, Masahiko"},{"full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","orcid":"0000-0001-8761-9444","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Marty, Alain","last_name":"Marty","first_name":"Alain"}],"_id":"693","file_date_updated":"2020-07-14T12:47:44Z","citation":{"ama":"Miki T, Kaufmann W, Malagon G, et al. Numbers of presynaptic Ca2+ channel clusters match those of functionally defined vesicular docking sites in single central synapses. <i>PNAS</i>. 2017;114(26):E5246-E5255. doi:<a href=\"https://doi.org/10.1073/pnas.1704470114\">10.1073/pnas.1704470114</a>","mla":"Miki, Takafumi, et al. “Numbers of Presynaptic Ca2+ Channel Clusters Match Those of Functionally Defined Vesicular Docking Sites in Single Central Synapses.” <i>PNAS</i>, vol. 114, no. 26, National Academy of Sciences, 2017, pp. E5246–55, doi:<a href=\"https://doi.org/10.1073/pnas.1704470114\">10.1073/pnas.1704470114</a>.","ieee":"T. Miki <i>et al.</i>, “Numbers of presynaptic Ca2+ channel clusters match those of functionally defined vesicular docking sites in single central synapses,” <i>PNAS</i>, vol. 114, no. 26. National Academy of Sciences, pp. E5246–E5255, 2017.","ista":"Miki T, Kaufmann W, Malagon G, Gomez L, Tabuchi K, Watanabe M, Shigemoto R, Marty A. 2017. Numbers of presynaptic Ca2+ channel clusters match those of functionally defined vesicular docking sites in single central synapses. PNAS. 114(26), E5246–E5255.","chicago":"Miki, Takafumi, Walter Kaufmann, Gerardo Malagon, Laura Gomez, Katsuhiko Tabuchi, Masahiko Watanabe, Ryuichi Shigemoto, and Alain Marty. “Numbers of Presynaptic Ca2+ Channel Clusters Match Those of Functionally Defined Vesicular Docking Sites in Single Central Synapses.” <i>PNAS</i>. National Academy of Sciences, 2017. <a href=\"https://doi.org/10.1073/pnas.1704470114\">https://doi.org/10.1073/pnas.1704470114</a>.","apa":"Miki, T., Kaufmann, W., Malagon, G., Gomez, L., Tabuchi, K., Watanabe, M., … Marty, A. (2017). Numbers of presynaptic Ca2+ channel clusters match those of functionally defined vesicular docking sites in single central synapses. <i>PNAS</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.1704470114\">https://doi.org/10.1073/pnas.1704470114</a>","short":"T. Miki, W. Kaufmann, G. Malagon, L. Gomez, K. Tabuchi, M. Watanabe, R. Shigemoto, A. Marty, PNAS 114 (2017) E5246–E5255."},"has_accepted_license":"1","scopus_import":"1","quality_controlled":"1","type":"journal_article","isi":1,"publisher":"National Academy of Sciences","intvolume":"       114","year":"2017","publication":"PNAS","external_id":{"isi":["000404108400028"],"pmid":["28607047"]},"title":"Numbers of presynaptic Ca2+ channel clusters match those of functionally defined vesicular docking sites in single central synapses","volume":114,"page":"E5246 - E5255","publist_id":"7013","department":[{"_id":"EM-Fac"},{"_id":"RySh"}],"publication_identifier":{"issn":["0027-8424"]},"date_created":"2018-12-11T11:47:57Z","article_processing_charge":"Yes (in subscription journal)","language":[{"iso":"eng"}],"oa":1,"issue":"26","oa_version":"Published Version","date_updated":"2025-09-10T14:00:03Z","file":[{"access_level":"open_access","creator":"kschuh","date_updated":"2020-07-14T12:47:44Z","relation":"main_file","content_type":"application/pdf","checksum":"2ab75d554f3df4a34d20fa8040589b7e","file_id":"7223","date_created":"2020-01-03T13:27:29Z","file_name":"2017_PNAS_Miki.pdf","file_size":2721544}],"corr_author":"1","day":"27","status":"public","date_published":"2017-06-27T00:00:00Z","abstract":[{"text":"Many central synapses contain a single presynaptic active zone and a single postsynaptic density. Vesicular release statistics at such “simple synapses” indicate that they contain a small complement of docking sites where vesicles repetitively dock and fuse. In this work, we investigate functional and morphological aspects of docking sites at simple synapses made between cerebellar parallel fibers and molecular layer interneurons. Using immunogold labeling of SDS-treated freeze-fracture replicas, we find that Cav2.1 channels form several clusters per active zone with about nine channels per cluster. The mean value and range of intersynaptic variation are similar for Cav2.1 cluster numbers and for functional estimates of docking-site numbers obtained from the maximum numbers of released vesicles per action potential. Both numbers grow in relation with synaptic size and decrease by a similar extent with age between 2 wk and 4 wk postnatal. Thus, the mean docking-site numbers were 3.15 at 2 wk (range: 1–10) and 2.03 at 4 wk (range: 1–4), whereas the mean numbers of Cav2.1 clusters were 2.84 at 2 wk (range: 1–8) and 2.37 at 4 wk (range: 1–5). These changes were accompanied by decreases of miniature current amplitude (from 93 pA to 56 pA), active-zone surface area (from 0.0427 μm2 to 0.0234 μm2), and initial success rate (from 0.609 to 0.353), indicating a tightening of synaptic transmission with development. Altogether, these results suggest a close correspondence between the number of functionally defined vesicular docking sites and that of clusters of voltage-gated calcium channels. ","lang":"eng"}],"publication_status":"published","ddc":["570"],"doi":"10.1073/pnas.1704470114","pmid":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","month":"06"},{"publication_status":"published","abstract":[{"text":"Adipose tissues play key roles in energy homeostasis. Brown adipocytes and beige adipocytes in white adipose tissue (WAT) share the similar characters of thermogenesis, both of them could be potential targets for obesity management. Several thermo-sensitive transient receptor potential channels (thermoTRPs) are shown to be involved in adipocyte biology. However, the expression pattern of thermoTRPs in adipose tissues from obese mice is still unknown. The mRNA expression of thermoTRPs in subcutaneous WAT (sWAT) and interscapular brown adipose tissue (iBAT) from lean and obese mice were measured using reverse transcriptase-quantitative PCRs (RT-qPCR). The results demonstrated that all 10 thermoTRPs are expressed in both iBAT and sWAT, and without significant difference in the mRNA expression level of thermoTRPs between these two tissues. Moreover, Trpv1 and Trpv3 mRNA expression levels in both iBAT and sWAT were significantly decreased in high fat diet (HFD)-induced obese mice and db/db (leptin receptor deficient) mice. Trpm2 mRNA expression level was significantly decreased only in sWAT from HFD-induced obese mice and db/db mice. On the other hand, Trpv2 and Trpv4 mRNA expression levels in iBAT and sWAT were significantly increased in HFD-induced obese mice and db/db mice. Taken together, we conclude that all 10 thermoTRPs are expressed in iBAT and sWAT. And several thermoTRPs differentially expressed in adipose tissues from HFD-induced obese mice and db/db mice, suggesting a potential involvement in anti-obesity regulations.","lang":"eng"}],"date_published":"2017-08-01T00:00:00Z","status":"public","month":"08","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","doi":"10.1002/cbin.10783","oa_version":"None","date_updated":"2025-09-10T11:03:51Z","issue":"8","language":[{"iso":"eng"}],"day":"01","publist_id":"6981","page":"908 - 913","volume":41,"external_id":{"isi":["000406246300010"]},"title":"Gene expression changes of thermo sensitive transient receptor potential channels in obese mice","publication":"Cell Biology International","year":"2017","article_processing_charge":"No","date_created":"2018-12-11T11:48:04Z","publication_identifier":{"issn":["1065-6995"]},"department":[{"_id":"RySh"}],"scopus_import":"1","quality_controlled":"1","citation":{"ama":"Sun W, Li C, Zhang Y, et al. Gene expression changes of thermo sensitive transient receptor potential channels in obese mice. <i>Cell Biology International</i>. 2017;41(8):908-913. doi:<a href=\"https://doi.org/10.1002/cbin.10783\">10.1002/cbin.10783</a>","mla":"Sun, Wuping, et al. “Gene Expression Changes of Thermo Sensitive Transient Receptor Potential Channels in Obese Mice.” <i>Cell Biology International</i>, vol. 41, no. 8, Wiley-Blackwell, 2017, pp. 908–13, doi:<a href=\"https://doi.org/10.1002/cbin.10783\">10.1002/cbin.10783</a>.","ieee":"W. Sun <i>et al.</i>, “Gene expression changes of thermo sensitive transient receptor potential channels in obese mice,” <i>Cell Biology International</i>, vol. 41, no. 8. Wiley-Blackwell, pp. 908–913, 2017.","ista":"Sun W, Li C, Zhang Y, Jiang C, Zhai M-Z, Zhou Q, Xiao L, Deng Q. 2017. Gene expression changes of thermo sensitive transient receptor potential channels in obese mice. Cell Biology International. 41(8), 908–913.","chicago":"Sun, Wuping, Chen Li, Yonghong Zhang, Changyu Jiang, Ming-Zhu Zhai, Qian Zhou, Lizu Xiao, and Qiwen Deng. “Gene Expression Changes of Thermo Sensitive Transient Receptor Potential Channels in Obese Mice.” <i>Cell Biology International</i>. Wiley-Blackwell, 2017. <a href=\"https://doi.org/10.1002/cbin.10783\">https://doi.org/10.1002/cbin.10783</a>.","short":"W. Sun, C. Li, Y. Zhang, C. Jiang, M.-Z. Zhai, Q. Zhou, L. Xiao, Q. Deng, Cell Biology International 41 (2017) 908–913.","apa":"Sun, W., Li, C., Zhang, Y., Jiang, C., Zhai, M.-Z., Zhou, Q., … Deng, Q. (2017). Gene expression changes of thermo sensitive transient receptor potential channels in obese mice. <i>Cell Biology International</i>. Wiley-Blackwell. <a href=\"https://doi.org/10.1002/cbin.10783\">https://doi.org/10.1002/cbin.10783</a>"},"_id":"709","author":[{"full_name":"Sun, Wuping","first_name":"Wuping","last_name":"Sun"},{"full_name":"Li, Chen","first_name":"Chen","last_name":"Li"},{"full_name":"Zhang, Yonghong","first_name":"Yonghong","last_name":"Zhang"},{"last_name":"Jiang","first_name":"Changyu","full_name":"Jiang, Changyu"},{"full_name":"Zhai, Ming-Zhu","last_name":"Zhai","id":"34009CFA-F248-11E8-B48F-1D18A9856A87","first_name":"Ming-Zhu"},{"full_name":"Zhou, Qian","last_name":"Zhou","first_name":"Qian"},{"first_name":"Lizu","last_name":"Xiao","full_name":"Xiao, Lizu"},{"full_name":"Deng, Qiwen","last_name":"Deng","first_name":"Qiwen"}],"intvolume":"        41","publisher":"Wiley-Blackwell","isi":1,"type":"journal_article"},{"isi":1,"type":"journal_article","intvolume":"       222","publisher":"Springer","_id":"736","file_date_updated":"2020-07-14T12:47:56Z","author":[{"full_name":"Rubio, María","first_name":"María","last_name":"Rubio"},{"full_name":"Matsui, Ko","first_name":"Ko","last_name":"Matsui"},{"full_name":"Fukazawa, Yugo","first_name":"Yugo","last_name":"Fukazawa"},{"last_name":"Kamasawa","first_name":"Naomi","full_name":"Kamasawa, Naomi"},{"full_name":"Harada, Harumi","first_name":"Harumi","last_name":"Harada","id":"2E55CDF2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7429-7896"},{"first_name":"Makoto","last_name":"Itakura","full_name":"Itakura, Makoto"},{"full_name":"Molnár, Elek","first_name":"Elek","last_name":"Molnár"},{"first_name":"Manabu","last_name":"Abe","full_name":"Abe, Manabu"},{"full_name":"Sakimura, Kenji","last_name":"Sakimura","first_name":"Kenji"},{"full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto","orcid":"0000-0001-8761-9444","first_name":"Ryuichi"}],"quality_controlled":"1","scopus_import":"1","has_accepted_license":"1","citation":{"mla":"Rubio, María, et al. “The Number and Distribution of AMPA Receptor Channels Containing Fast Kinetic GluA3 and GluA4 Subunits at Auditory Nerve Synapses Depend on the Target Cells.” <i>Brain Structure and Function</i>, vol. 222, no. 8, Springer, 2017, pp. 3375–93, doi:<a href=\"https://doi.org/10.1007/s00429-017-1408-0\">10.1007/s00429-017-1408-0</a>.","ieee":"M. Rubio <i>et al.</i>, “The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells,” <i>Brain Structure and Function</i>, vol. 222, no. 8. Springer, pp. 3375–3393, 2017.","ista":"Rubio M, Matsui K, Fukazawa Y, Kamasawa N, Harada H, Itakura M, Molnár E, Abe M, Sakimura K, Shigemoto R. 2017. The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells. Brain Structure and Function. 222(8), 3375–3393.","ama":"Rubio M, Matsui K, Fukazawa Y, et al. The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells. <i>Brain Structure and Function</i>. 2017;222(8):3375-3393. doi:<a href=\"https://doi.org/10.1007/s00429-017-1408-0\">10.1007/s00429-017-1408-0</a>","apa":"Rubio, M., Matsui, K., Fukazawa, Y., Kamasawa, N., Harada, H., Itakura, M., … Shigemoto, R. (2017). The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells. <i>Brain Structure and Function</i>. Springer. <a href=\"https://doi.org/10.1007/s00429-017-1408-0\">https://doi.org/10.1007/s00429-017-1408-0</a>","short":"M. Rubio, K. Matsui, Y. Fukazawa, N. Kamasawa, H. Harada, M. Itakura, E. Molnár, M. Abe, K. Sakimura, R. Shigemoto, Brain Structure and Function 222 (2017) 3375–3393.","chicago":"Rubio, María, Ko Matsui, Yugo Fukazawa, Naomi Kamasawa, Harumi Harada, Makoto Itakura, Elek Molnár, Manabu Abe, Kenji Sakimura, and Ryuichi Shigemoto. “The Number and Distribution of AMPA Receptor Channels Containing Fast Kinetic GluA3 and GluA4 Subunits at Auditory Nerve Synapses Depend on the Target Cells.” <i>Brain Structure and Function</i>. Springer, 2017. <a href=\"https://doi.org/10.1007/s00429-017-1408-0\">https://doi.org/10.1007/s00429-017-1408-0</a>."},"department":[{"_id":"RySh"}],"article_processing_charge":"No","date_created":"2018-12-11T11:48:14Z","publication_identifier":{"issn":["1863-2653"]},"volume":222,"external_id":{"isi":["000414761700002"]},"title":"The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells","publication":"Brain Structure and Function","year":"2017","publist_id":"6932","page":"3375 - 3393","pubrep_id":"881","file":[{"date_created":"2018-12-12T10:10:20Z","file_id":"4806","checksum":"73787a22507de8fb585bb598e1418ca7","file_size":4011126,"file_name":"IST-2017-881-v1+1_s00429-017-1408-0.pdf","date_updated":"2020-07-14T12:47:56Z","creator":"system","access_level":"open_access","content_type":"application/pdf","relation":"main_file"}],"day":"01","oa":1,"language":[{"iso":"eng"}],"oa_version":"Published Version","date_updated":"2025-07-10T11:54:32Z","issue":"8","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","doi":"10.1007/s00429-017-1408-0","month":"11","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"date_published":"2017-11-01T00:00:00Z","status":"public","ddc":["571"],"abstract":[{"text":"The neurotransmitter receptor subtype, number, density, and distribution relative to the location of transmitter release sites are key determinants of signal transmission. AMPA-type ionotropic glutamate receptors (AMPARs) containing GluA3 and GluA4 subunits are prominently expressed in subsets of neurons capable of firing action potentials at high frequencies, such as auditory relay neurons. The auditory nerve (AN) forms glutamatergic synapses on two types of relay neurons, bushy cells (BCs) and fusiform cells (FCs) of the cochlear nucleus. AN-BC and AN-FC synapses have distinct kinetics; thus, we investigated whether the number, density, and localization of GluA3 and GluA4 subunits in these synapses are differentially organized using quantitative freeze-fracture replica immunogold labeling. We identify a positive correlation between the number of AMPARs and the size of AN-BC and AN-FC synapses. Both types of AN synapses have similar numbers of AMPARs; however, the AN-BC have a higher density of AMPARs than AN-FC synapses, because the AN-BC synapses are smaller. A higher number and density of GluA3 subunits are observed at AN-BC synapses, whereas a higher number and density of GluA4 subunits are observed at AN-FC synapses. The intrasynaptic distribution of immunogold labeling revealed that AMPAR subunits, particularly GluA3, are concentrated at the center of the AN-BC synapses. The central distribution of AMPARs is absent in GluA3-knockout mice, and gold particles are evenly distributed along the postsynaptic density. GluA4 gold labeling was homogenously distributed along both synapse types. Thus, GluA3 and GluA4 subunits are distributed at AN synapses in a target-cell-dependent manner.","lang":"eng"}],"publication_status":"published"},{"corr_author":"1","file":[{"content_type":"application/pdf","relation":"main_file","creator":"dernst","access_level":"open_access","date_updated":"2020-07-14T12:47:57Z","file_size":1647787,"file_name":"2017_WIREs_Shigemoto.pdf","checksum":"a9370f27b1591773b7a0de299bc81c8c","date_created":"2019-11-19T07:36:18Z","file_id":"7045"}],"day":"11","language":[{"iso":"eng"}],"oa":1,"oa_version":"Submitted Version","date_updated":"2025-07-10T11:54:34Z","issue":"6","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","doi":"10.1002/wdev.288","pmid":1,"month":"08","tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","short":"CC BY-NC (4.0)","image":"/images/cc_by_nc.png"},"date_published":"2017-08-11T00:00:00Z","status":"public","ddc":["570"],"publication_status":"published","abstract":[{"lang":"eng","text":"Developments in bioengineering and molecular biology have introduced a palette of genetically encoded probes for identification of specific cell populations in electron microscopy. These probes can be targeted to distinct cellular compartments, rendering them electron dense through a subsequent chemical reaction. These electron densities strongly increase the local contrast in samples prepared for electron microscopy, allowing three major advances in ultrastructural mapping of circuits: genetic identification of circuit components, targeted imaging of regions of interest and automated analysis of the tagged circuits. Together, the gains from these advances can decrease the time required for the analysis of targeted circuit motifs by over two orders of magnitude. These genetic encoded tags for electron microscopy promise to simplify the analysis of circuit motifs and become a central tool for structure‐function studies of synaptic connections in the brain. We review the current state‐of‐the‐art with an emphasis on connectomics, the quantitative analysis of neuronal structures and motifs."}],"isi":1,"type":"journal_article","intvolume":"         6","publisher":"Wiley-Blackwell","file_date_updated":"2020-07-14T12:47:57Z","_id":"740","author":[{"full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto","orcid":"0000-0001-8761-9444","first_name":"Ryuichi"},{"full_name":"Jösch, Maximilian A","first_name":"Maximilian A","orcid":"0000-0002-3937-1330","last_name":"Jösch","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87"}],"scopus_import":"1","quality_controlled":"1","article_number":"e288","has_accepted_license":"1","citation":{"apa":"Shigemoto, R., &#38; Jösch, M. A. (2017). The genetic encoded toolbox for electron microscopy and connectomics. <i>WIREs Developmental Biology</i>. Wiley-Blackwell. <a href=\"https://doi.org/10.1002/wdev.288\">https://doi.org/10.1002/wdev.288</a>","short":"R. Shigemoto, M.A. Jösch, WIREs Developmental Biology 6 (2017).","chicago":"Shigemoto, Ryuichi, and Maximilian A Jösch. “The Genetic Encoded Toolbox for Electron Microscopy and Connectomics.” <i>WIREs Developmental Biology</i>. Wiley-Blackwell, 2017. <a href=\"https://doi.org/10.1002/wdev.288\">https://doi.org/10.1002/wdev.288</a>.","mla":"Shigemoto, Ryuichi, and Maximilian A. Jösch. “The Genetic Encoded Toolbox for Electron Microscopy and Connectomics.” <i>WIREs Developmental Biology</i>, vol. 6, no. 6, e288, Wiley-Blackwell, 2017, doi:<a href=\"https://doi.org/10.1002/wdev.288\">10.1002/wdev.288</a>.","ista":"Shigemoto R, Jösch MA. 2017. The genetic encoded toolbox for electron microscopy and connectomics. WIREs Developmental Biology. 6(6), e288.","ieee":"R. Shigemoto and M. A. Jösch, “The genetic encoded toolbox for electron microscopy and connectomics,” <i>WIREs Developmental Biology</i>, vol. 6, no. 6. Wiley-Blackwell, 2017.","ama":"Shigemoto R, Jösch MA. The genetic encoded toolbox for electron microscopy and connectomics. <i>WIREs Developmental Biology</i>. 2017;6(6). doi:<a href=\"https://doi.org/10.1002/wdev.288\">10.1002/wdev.288</a>"},"department":[{"_id":"RySh"},{"_id":"MaJö"}],"article_processing_charge":"No","date_created":"2018-12-11T11:48:15Z","publication_identifier":{"issn":["1759-7684"]},"volume":6,"external_id":{"isi":["000412827400005"],"pmid":["28800674"]},"title":"The genetic encoded toolbox for electron microscopy and connectomics","article_type":"original","publication":"WIREs Developmental Biology","year":"2017","publist_id":"6927"},{"intvolume":"         8","publisher":"Nature Publishing Group","type":"journal_article","isi":1,"has_accepted_license":"1","article_number":"1103","scopus_import":"1","quality_controlled":"1","citation":{"ieee":"E. Aloisi <i>et al.</i>, “Altered surface mGluR5 dynamics provoke synaptic NMDAR dysfunction and cognitive defects in Fmr1 knockout mice,” <i>Nature Communications</i>, vol. 8, no. 1. Nature Publishing Group, 2017.","mla":"Aloisi, Elisabetta, et al. “Altered Surface MGluR5 Dynamics Provoke Synaptic NMDAR Dysfunction and Cognitive Defects in Fmr1 Knockout Mice.” <i>Nature Communications</i>, vol. 8, no. 1, 1103, Nature Publishing Group, 2017, doi:<a href=\"https://doi.org/10.1038/s41467-017-01191-2\">10.1038/s41467-017-01191-2</a>.","ista":"Aloisi E, Le Corf K, Dupuis J, Zhang P, Ginger M, Labrousse V, Spatuzza M, Georg Haberl M, Costa L, Shigemoto R, Tappe Theodor A, Drago F, Vincenzo Piazza P, Mulle C, Groc L, Ciranna L, Catania M, Frick A. 2017. Altered surface mGluR5 dynamics provoke synaptic NMDAR dysfunction and cognitive defects in Fmr1 knockout mice. Nature Communications. 8(1), 1103.","ama":"Aloisi E, Le Corf K, Dupuis J, et al. Altered surface mGluR5 dynamics provoke synaptic NMDAR dysfunction and cognitive defects in Fmr1 knockout mice. <i>Nature Communications</i>. 2017;8(1). doi:<a href=\"https://doi.org/10.1038/s41467-017-01191-2\">10.1038/s41467-017-01191-2</a>","short":"E. Aloisi, K. Le Corf, J. Dupuis, P. Zhang, M. Ginger, V. Labrousse, M. Spatuzza, M. Georg Haberl, L. Costa, R. Shigemoto, A. Tappe Theodor, F. Drago, P. Vincenzo Piazza, C. Mulle, L. Groc, L. Ciranna, M. Catania, A. Frick, Nature Communications 8 (2017).","apa":"Aloisi, E., Le Corf, K., Dupuis, J., Zhang, P., Ginger, M., Labrousse, V., … Frick, A. (2017). Altered surface mGluR5 dynamics provoke synaptic NMDAR dysfunction and cognitive defects in Fmr1 knockout mice. <i>Nature Communications</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/s41467-017-01191-2\">https://doi.org/10.1038/s41467-017-01191-2</a>","chicago":"Aloisi, Elisabetta, Katy Le Corf, Julien Dupuis, Pei Zhang, Melanie Ginger, Virginie Labrousse, Michela Spatuzza, et al. “Altered Surface MGluR5 Dynamics Provoke Synaptic NMDAR Dysfunction and Cognitive Defects in Fmr1 Knockout Mice.” <i>Nature Communications</i>. Nature Publishing Group, 2017. <a href=\"https://doi.org/10.1038/s41467-017-01191-2\">https://doi.org/10.1038/s41467-017-01191-2</a>."},"author":[{"full_name":"Aloisi, Elisabetta","last_name":"Aloisi","first_name":"Elisabetta"},{"first_name":"Katy","last_name":"Le Corf","full_name":"Le Corf, Katy"},{"last_name":"Dupuis","first_name":"Julien","full_name":"Dupuis, Julien"},{"first_name":"Pei","last_name":"Zhang","full_name":"Zhang, Pei"},{"last_name":"Ginger","first_name":"Melanie","full_name":"Ginger, Melanie"},{"first_name":"Virginie","last_name":"Labrousse","full_name":"Labrousse, Virginie"},{"full_name":"Spatuzza, Michela","last_name":"Spatuzza","first_name":"Michela"},{"full_name":"Georg Haberl, Matthias","last_name":"Georg Haberl","first_name":"Matthias"},{"full_name":"Costa, Lara","last_name":"Costa","first_name":"Lara"},{"full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto","orcid":"0000-0001-8761-9444","first_name":"Ryuichi"},{"last_name":"Tappe Theodor","first_name":"Anke","full_name":"Tappe Theodor, Anke"},{"first_name":"Fillippo","last_name":"Drago","full_name":"Drago, Fillippo"},{"first_name":"Pier","last_name":"Vincenzo Piazza","full_name":"Vincenzo Piazza, Pier"},{"full_name":"Mulle, Christophe","last_name":"Mulle","first_name":"Christophe"},{"first_name":"Laurent","last_name":"Groc","full_name":"Groc, Laurent"},{"first_name":"Lucia","last_name":"Ciranna","full_name":"Ciranna, Lucia"},{"full_name":"Catania, Maria","last_name":"Catania","first_name":"Maria"},{"full_name":"Frick, Andreas","first_name":"Andreas","last_name":"Frick"}],"file_date_updated":"2020-07-14T12:47:58Z","_id":"746","date_created":"2018-12-11T11:48:17Z","article_processing_charge":"No","publication_identifier":{"issn":["2041-1723"]},"department":[{"_id":"RySh"}],"pubrep_id":"915","publist_id":"6921","title":"Altered surface mGluR5 dynamics provoke synaptic NMDAR dysfunction and cognitive defects in Fmr1 knockout mice","external_id":{"isi":["000413571300004"]},"volume":8,"year":"2017","publication":"Nature Communications","day":"01","file":[{"file_size":1841650,"file_name":"IST-2017-915-v1+1_s41467-017-01191-2.pdf","date_created":"2018-12-12T10:17:32Z","file_id":"5287","checksum":"99ceee57549dc0461e3adfc037ec70a9","content_type":"application/pdf","relation":"main_file","date_updated":"2020-07-14T12:47:58Z","creator":"system","access_level":"open_access"}],"issue":"1","oa_version":"Published Version","date_updated":"2025-07-10T11:54:38Z","language":[{"iso":"eng"}],"oa":1,"tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"month":"12","doi":"10.1038/s41467-017-01191-2","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_status":"published","abstract":[{"text":"Metabotropic glutamate receptor subtype 5 (mGluR5) is crucially implicated in the pathophysiology of Fragile X Syndrome (FXS); however, its dysfunction at the sub-cellular level, and related synaptic and cognitive phenotypes are unexplored. Here, we probed the consequences of mGluR5/Homer scaffold disruption for mGluR5 cell-surface mobility, synaptic N-methyl-D-Aspartate receptor (NMDAR) function, and behavioral phenotypes in the second-generation Fmr1 knockout (KO) mouse. Using single-molecule tracking, we found that mGluR5 was significantly more mobile at synapses in hippocampal Fmr1 KO neurons, causing an increased synaptic surface co-clustering of mGluR5 and NMDAR. This correlated with a reduced amplitude of synaptic NMDAR currents, a lack of their mGluR5-Activated long-Term depression, and NMDAR/hippocampus dependent cognitive deficits. These synaptic and behavioral phenomena were reversed by knocking down Homer1a in Fmr1 KO mice. Our study provides a mechanistic link between changes of mGluR5 dynamics and pathological phenotypes of FXS, unveiling novel targets for mGluR5-based therapeutics.","lang":"eng"}],"ddc":["571"],"date_published":"2017-12-01T00:00:00Z","status":"public"},{"publication_identifier":{"issn":["1932-6203"]},"date_created":"2018-12-11T11:47:54Z","article_processing_charge":"No","department":[{"_id":"RySh"}],"related_material":{"record":[{"id":"51","status":"public","relation":"dissertation_contains"}]},"pubrep_id":"897","publist_id":"7034","year":"2017","publication":"PLoS One","external_id":{"isi":["000402923200125"]},"article_type":"original","title":"PirB regulates asymmetries in hippocampal circuitry","volume":12,"publisher":"Public Library of Science","intvolume":"        12","type":"journal_article","isi":1,"citation":{"apa":"Ukai, H., Kawahara, A., Hirayama, K., Case, M. J., Aino, S., Miyabe, M., … Ito, I. (2017). PirB regulates asymmetries in hippocampal circuitry. <i>PLoS One</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pone.0179377\">https://doi.org/10.1371/journal.pone.0179377</a>","short":"H. Ukai, A. Kawahara, K. Hirayama, M.J. Case, S. Aino, M. Miyabe, K. Wakita, R. Oogi, M. Kasayuki, S. Kawashima, S. Sugimoto, K. Chikamatsu, N. Nitta, T. Koga, R. Shigemoto, T. Takai, I. Ito, PLoS One 12 (2017).","chicago":"Ukai, Hikari, Aiko Kawahara, Keiko Hirayama, Matthew J Case, Shotaro Aino, Masahiro Miyabe, Ken Wakita, et al. “PirB Regulates Asymmetries in Hippocampal Circuitry.” <i>PLoS One</i>. Public Library of Science, 2017. <a href=\"https://doi.org/10.1371/journal.pone.0179377\">https://doi.org/10.1371/journal.pone.0179377</a>.","mla":"Ukai, Hikari, et al. “PirB Regulates Asymmetries in Hippocampal Circuitry.” <i>PLoS One</i>, vol. 12, no. 6, e0179377, Public Library of Science, 2017, doi:<a href=\"https://doi.org/10.1371/journal.pone.0179377\">10.1371/journal.pone.0179377</a>.","ieee":"H. Ukai <i>et al.</i>, “PirB regulates asymmetries in hippocampal circuitry,” <i>PLoS One</i>, vol. 12, no. 6. Public Library of Science, 2017.","ista":"Ukai H, Kawahara A, Hirayama K, Case MJ, Aino S, Miyabe M, Wakita K, Oogi R, Kasayuki M, Kawashima S, Sugimoto S, Chikamatsu K, Nitta N, Koga T, Shigemoto R, Takai T, Ito I. 2017. PirB regulates asymmetries in hippocampal circuitry. PLoS One. 12(6), e0179377.","ama":"Ukai H, Kawahara A, Hirayama K, et al. PirB regulates asymmetries in hippocampal circuitry. <i>PLoS One</i>. 2017;12(6). doi:<a href=\"https://doi.org/10.1371/journal.pone.0179377\">10.1371/journal.pone.0179377</a>"},"has_accepted_license":"1","article_number":"e0179377","quality_controlled":"1","scopus_import":"1","author":[{"last_name":"Ukai","first_name":"Hikari","full_name":"Ukai, Hikari"},{"first_name":"Aiko","last_name":"Kawahara","full_name":"Kawahara, Aiko"},{"first_name":"Keiko","last_name":"Hirayama","full_name":"Hirayama, Keiko"},{"full_name":"Case, Matthew J","last_name":"Case","id":"44B7CA5A-F248-11E8-B48F-1D18A9856A87","first_name":"Matthew J"},{"full_name":"Aino, Shotaro","first_name":"Shotaro","last_name":"Aino"},{"last_name":"Miyabe","first_name":"Masahiro","full_name":"Miyabe, Masahiro"},{"first_name":"Ken","last_name":"Wakita","full_name":"Wakita, Ken"},{"full_name":"Oogi, Ryohei","last_name":"Oogi","first_name":"Ryohei"},{"full_name":"Kasayuki, Michiyo","first_name":"Michiyo","last_name":"Kasayuki"},{"last_name":"Kawashima","first_name":"Shihomi","full_name":"Kawashima, Shihomi"},{"full_name":"Sugimoto, Shunichi","first_name":"Shunichi","last_name":"Sugimoto"},{"last_name":"Chikamatsu","first_name":"Kanako","full_name":"Chikamatsu, Kanako"},{"last_name":"Nitta","first_name":"Noritaka","full_name":"Nitta, Noritaka"},{"full_name":"Koga, Tsuneyuki","first_name":"Tsuneyuki","last_name":"Koga"},{"full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444"},{"full_name":"Takai, Toshiyuki","last_name":"Takai","first_name":"Toshiyuki"},{"full_name":"Ito, Isao","first_name":"Isao","last_name":"Ito"}],"file_date_updated":"2020-07-14T12:47:40Z","_id":"682","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"month":"06","doi":"10.1371/journal.pone.0179377","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","publication_status":"published","abstract":[{"text":"Left-right asymmetry is a fundamental feature of higher-order brain structure; however, the molecular basis of brain asymmetry remains unclear. We recently identified structural and functional asymmetries in mouse hippocampal circuitry that result from the asymmetrical distribution of two distinct populations of pyramidal cell synapses that differ in the density of the NMDA receptor subunit GluRε2 (also known as NR2B, GRIN2B or GluN2B). By examining the synaptic distribution of ε2 subunits, we previously found that β2-microglobulin-deficient mice, which lack cell surface expression of the vast majority of major histocompatibility complex class I (MHCI) proteins, do not exhibit circuit asymmetry. In the present study, we conducted electrophysiological and anatomical analyses on the hippocampal circuitry of mice with a knockout of the paired immunoglobulin-like receptor B (PirB), an MHCI receptor. As in β2-microglobulin-deficient mice, the PirB-deficient hippocampus lacked circuit asymmetries. This finding that MHCI loss-of-function mice and PirB knockout mice have identical phenotypes suggests that MHCI signals that produce hippocampal asymmetries are transduced through PirB. Our results provide evidence for a critical role of the MHCI/PirB signaling system in the generation of asymmetries in hippocampal circuitry.","lang":"eng"}],"ddc":["571"],"status":"public","date_published":"2017-06-01T00:00:00Z","day":"01","file":[{"file_name":"IST-2017-897-v1+1_journal.pone.0179377.pdf","file_size":5798454,"file_id":"4934","date_created":"2018-12-12T10:12:16Z","checksum":"24dd19c46fb1c761b0bcbbcd1025a3a8","relation":"main_file","content_type":"application/pdf","date_updated":"2020-07-14T12:47:40Z","access_level":"open_access","creator":"system"}],"issue":"6","oa_version":"Published Version","date_updated":"2026-05-02T22:30:55Z","language":[{"iso":"eng"}],"oa":1},{"publist_id":"6038","pubrep_id":"689","volume":11,"external_id":{"isi":["000385697600069"]},"article_type":"original","title":"Distribution and structure of synapses on medial vestibular nuclear neurons targeted by cerebellar flocculus purkinje cells and vestibular nerve in mice: Light and electron microscopy studies","publication":"PLoS One","year":"2016","article_processing_charge":"No","date_created":"2018-12-11T11:51:06Z","acknowledgement":"This work was supported by RIKEN [to SN]; Grant-in-Aid from the Japan Society for the Promotion of Science, https://www.jsps.go.jp/english/e-grants/ [22300112 to SN].","department":[{"_id":"RySh"}],"scopus_import":"1","quality_controlled":"1","article_number":"e0164037","has_accepted_license":"1","citation":{"ama":"Matsuno H, Kudoh M, Watakabe A, Yamamori T, Shigemoto R, Nagao S. Distribution and structure of synapses on medial vestibular nuclear neurons targeted by cerebellar flocculus purkinje cells and vestibular nerve in mice: Light and electron microscopy studies. <i>PLoS One</i>. 2016;11(10). doi:<a href=\"https://doi.org/10.1371/journal.pone.0164037\">10.1371/journal.pone.0164037</a>","ista":"Matsuno H, Kudoh M, Watakabe A, Yamamori T, Shigemoto R, Nagao S. 2016. Distribution and structure of synapses on medial vestibular nuclear neurons targeted by cerebellar flocculus purkinje cells and vestibular nerve in mice: Light and electron microscopy studies. PLoS One. 11(10), e0164037.","mla":"Matsuno, Hitomi, et al. “Distribution and Structure of Synapses on Medial Vestibular Nuclear Neurons Targeted by Cerebellar Flocculus Purkinje Cells and Vestibular Nerve in Mice: Light and Electron Microscopy Studies.” <i>PLoS One</i>, vol. 11, no. 10, e0164037, Public Library of Science, 2016, doi:<a href=\"https://doi.org/10.1371/journal.pone.0164037\">10.1371/journal.pone.0164037</a>.","ieee":"H. Matsuno, M. Kudoh, A. Watakabe, T. Yamamori, R. Shigemoto, and S. Nagao, “Distribution and structure of synapses on medial vestibular nuclear neurons targeted by cerebellar flocculus purkinje cells and vestibular nerve in mice: Light and electron microscopy studies,” <i>PLoS One</i>, vol. 11, no. 10. Public Library of Science, 2016.","chicago":"Matsuno, Hitomi, Moeko Kudoh, Akiya Watakabe, Tetsuo Yamamori, Ryuichi Shigemoto, and Soichi Nagao. “Distribution and Structure of Synapses on Medial Vestibular Nuclear Neurons Targeted by Cerebellar Flocculus Purkinje Cells and Vestibular Nerve in Mice: Light and Electron Microscopy Studies.” <i>PLoS One</i>. Public Library of Science, 2016. <a href=\"https://doi.org/10.1371/journal.pone.0164037\">https://doi.org/10.1371/journal.pone.0164037</a>.","apa":"Matsuno, H., Kudoh, M., Watakabe, A., Yamamori, T., Shigemoto, R., &#38; Nagao, S. (2016). Distribution and structure of synapses on medial vestibular nuclear neurons targeted by cerebellar flocculus purkinje cells and vestibular nerve in mice: Light and electron microscopy studies. <i>PLoS One</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pone.0164037\">https://doi.org/10.1371/journal.pone.0164037</a>","short":"H. Matsuno, M. Kudoh, A. Watakabe, T. Yamamori, R. Shigemoto, S. Nagao, PLoS One 11 (2016)."},"_id":"1278","file_date_updated":"2020-07-14T12:44:42Z","author":[{"last_name":"Matsuno","first_name":"Hitomi","full_name":"Matsuno, Hitomi"},{"last_name":"Kudoh","first_name":"Moeko","full_name":"Kudoh, Moeko"},{"first_name":"Akiya","last_name":"Watakabe","full_name":"Watakabe, Akiya"},{"full_name":"Yamamori, Tetsuo","first_name":"Tetsuo","last_name":"Yamamori"},{"first_name":"Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi"},{"first_name":"Soichi","last_name":"Nagao","full_name":"Nagao, Soichi"}],"intvolume":"        11","publisher":"Public Library of Science","isi":1,"type":"journal_article","ddc":["570","571"],"publication_status":"published","abstract":[{"text":"Adaptations of vestibulo-ocular and optokinetic response eye movements have been studied as an experimental model of cerebellum-dependent motor learning. Several previous physiological and pharmacological studies have consistently suggested that the cerebellar flocculus (FL) Purkinje cells (P-cells) and the medial vestibular nucleus (MVN) neurons targeted by FL (FL-targeted MVN neurons) may respectively maintain the memory traces of short- and long-term adaptation. To study the basic structures of the FL-MVN synapses by light microscopy (LM) and electron microscopy (EM), we injected green florescence protein (GFP)-expressing lentivirus into FL to anterogradely label the FL P-cell axons in C57BL/6J mice. The FL P-cell axonal boutons were distributed in the magnocellular MVN and in the border region of parvocellular MVN and prepositus hypoglossi (PrH). In the magnocellular MVN, the FL-P cell axons mainly terminated on somata and proximal dendrites. On the other hand, in the parvocellular MVN/PrH, the FL P-cell axonal synaptic boutons mainly terminated on the relatively small-diameter (&lt; 1 μm) distal dendrites of MVN neurons, forming symmetrical synapses. The majority of such parvocellular MVN/PrH neurons were determined to be glutamatergic by immunocytochemistry and in-situ hybridization of GFP expressing transgenic mice. To further examine the spatial relationship between the synapses of FL P-cells and those of vestibular nerve on the neurons of the parvocellular MVN/ PrH, we added injections of biotinylated dextran amine into the semicircular canal and anterogradely labeled vestibular nerve axons in some mice. The MVN dendrites receiving the FL P-cell axonal synaptic boutons often closely apposed vestibular nerve synaptic boutons in both LM and EM studies. Such a partial overlap of synaptic boutons of FL P-cell axons with those of vestibular nerve axons in the distal dendrites of MVN neurons suggests that inhibitory synapses of FL P-cells may influence the function of neighboring excitatory synapses of vestibular nerve in the parvocellular MVN/PrH neurons.","lang":"eng"}],"date_published":"2016-10-06T00:00:00Z","status":"public","month":"10","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","doi":"10.1371/journal.pone.0164037","oa_version":"Published Version","date_updated":"2025-09-22T08:37:04Z","issue":"10","oa":1,"language":[{"iso":"eng"}],"day":"06","file":[{"access_level":"open_access","creator":"system","date_updated":"2020-07-14T12:44:42Z","relation":"main_file","content_type":"application/pdf","checksum":"7c0ba0ca6d79844059158059d2a38d25","file_id":"5269","date_created":"2018-12-12T10:17:16Z","file_size":3657084,"file_name":"IST-2016-689-v1+1_journal.pone.0164037.PDF"}]},{"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","doi":"10.1093/cercor/bhw090","month":"04","status":"public","date_published":"2016-04-12T00:00:00Z","abstract":[{"lang":"eng","text":" Cholecystokinin-expressing interneurons (CCK-INs) mediate behavior state-dependent inhibition in cortical circuits and themselves receive strong GABAergic input. However, it remains unclear to what extent GABABreceptors (GABABRs) contribute to their inhibitory control. Using immunoelectron microscopy, we found that CCK-INs in the rat hippocampus possessed high levels of dendritic GABABRs and KCTD12 auxiliary proteins, whereas postsynaptic effector Kir3 channels were present at lower levels. Consistently, whole-cell recordings revealed slow GABABR-mediated inhibitory postsynaptic currents (IPSCs) in most CCK-INs. In spite of the higher surface density of GABABRs in CCK-INs than in CA1 principal cells, the amplitudes of IPSCs were comparable, suggesting that the expression of Kir3 channels is the limiting factor for the GABABR currents in these INs. Morphological analysis showed that CCK-INs were diverse, comprising perisomatic-targeting basket cells (BCs), as well as dendrite-targeting (DT) interneurons, including a previously undescribed DT type. GABABR-mediated IPSCs in CCK-INs were large in BCs, but small in DT subtypes. In response to prolonged activation, GABABR-mediated currents displayed strong desensitization, which was absent in KCTD12-deficient mice. This study highlights that GABABRs differentially control CCK-IN subtypes, and the kinetics and desensitization of GABABR-mediated currents are modulated by KCTD12 proteins. "}],"publication_status":"published","day":"12","language":[{"iso":"eng"}],"oa_version":"None","date_updated":"2025-09-22T14:19:11Z","issue":"3","department":[{"_id":"RySh"}],"article_processing_charge":"No","date_created":"2018-12-11T11:50:03Z","acknowledgement":"This work was supported by the Deutsche Forschungsgemeinschaft (DFG SFB 780 A2, A.K.; SFB TR3 I.V. and EXC 257, I.V.; FOR 2143, A.K. and I.V.), Spemann Graduate School (D.A.), BIOSS-2 (A6, A.K.), the Swiss National Science Foundation (3100A0-117816, B.B.), The McNaught Bequest (S.A.B. and I.V.), and Tenovus Scotland (I.V.).\r\n\r\n\r\nWe thank Cheryl Hutton and Chinmaya Sadangi for their contributions to neuronal reconstruction as well as Natalie Wernet, Sigrun Nestel, Anikó Schneider, Ina Wolter, and Ulrich Noeller for their excellent technical support. VGAT-Venus transgenic rats were generated by Drs Y. Yanagawa, M. Hirabayashi, and Y. Kawaguchi in National Institute for Physiological Sciences, Okazaki, Japan, using pCS2-Venus provided by Dr A. Miyawaki. The monoclonal mouse CCK antibody was generously provided by Dr G.V. Ohning, CURE Center, UCLA, CA. ","publication":"Cerebral Cortex","year":"2016","volume":27,"title":"KCTD12 auxiliary proteins modulate kinetics of GABAB receptor-mediated inhibition in Cholecystokinin-containing interneurons","external_id":{"isi":["000397636600048"]},"publist_id":"6297","page":"2318 - 2334","isi":1,"type":"journal_article","publisher":"Oxford University Press","intvolume":"        27","_id":"1083","author":[{"full_name":"Booker, Sam","last_name":"Booker","first_name":"Sam"},{"first_name":"Daniel","last_name":"Althof","full_name":"Althof, Daniel"},{"full_name":"Gross, Anna","first_name":"Anna","last_name":"Gross"},{"first_name":"Desiree","last_name":"Loreth","full_name":"Loreth, Desiree"},{"full_name":"Müller, Johanna","first_name":"Johanna","last_name":"Müller"},{"last_name":"Unger","first_name":"Andreas","full_name":"Unger, Andreas"},{"full_name":"Fakler, Bernd","last_name":"Fakler","first_name":"Bernd"},{"last_name":"Varro","first_name":"Andrea","full_name":"Varro, Andrea"},{"full_name":"Watanabe, Masahiko","last_name":"Watanabe","first_name":"Masahiko"},{"first_name":"Martin","last_name":"Gassmann","full_name":"Gassmann, Martin"},{"full_name":"Bettler, Bernhard","last_name":"Bettler","first_name":"Bernhard"},{"full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto","first_name":"Ryuichi"},{"full_name":"Vida, Imre","last_name":"Vida","first_name":"Imre"},{"full_name":"Kulik, Ákos","first_name":"Ákos","last_name":"Kulik"}],"citation":{"short":"S. Booker, D. Althof, A. Gross, D. Loreth, J. Müller, A. Unger, B. Fakler, A. Varro, M. Watanabe, M. Gassmann, B. Bettler, R. Shigemoto, I. Vida, Á. Kulik, Cerebral Cortex 27 (2016) 2318–2334.","apa":"Booker, S., Althof, D., Gross, A., Loreth, D., Müller, J., Unger, A., … Kulik, Á. (2016). KCTD12 auxiliary proteins modulate kinetics of GABAB receptor-mediated inhibition in Cholecystokinin-containing interneurons. <i>Cerebral Cortex</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/cercor/bhw090\">https://doi.org/10.1093/cercor/bhw090</a>","chicago":"Booker, Sam, Daniel Althof, Anna Gross, Desiree Loreth, Johanna Müller, Andreas Unger, Bernd Fakler, et al. “KCTD12 Auxiliary Proteins Modulate Kinetics of GABAB Receptor-Mediated Inhibition in Cholecystokinin-Containing Interneurons.” <i>Cerebral Cortex</i>. Oxford University Press, 2016. <a href=\"https://doi.org/10.1093/cercor/bhw090\">https://doi.org/10.1093/cercor/bhw090</a>.","ieee":"S. Booker <i>et al.</i>, “KCTD12 auxiliary proteins modulate kinetics of GABAB receptor-mediated inhibition in Cholecystokinin-containing interneurons,” <i>Cerebral Cortex</i>, vol. 27, no. 3. Oxford University Press, pp. 2318–2334, 2016.","ista":"Booker S, Althof D, Gross A, Loreth D, Müller J, Unger A, Fakler B, Varro A, Watanabe M, Gassmann M, Bettler B, Shigemoto R, Vida I, Kulik Á. 2016. KCTD12 auxiliary proteins modulate kinetics of GABAB receptor-mediated inhibition in Cholecystokinin-containing interneurons. Cerebral Cortex. 27(3), 2318–2334.","mla":"Booker, Sam, et al. “KCTD12 Auxiliary Proteins Modulate Kinetics of GABAB Receptor-Mediated Inhibition in Cholecystokinin-Containing Interneurons.” <i>Cerebral Cortex</i>, vol. 27, no. 3, Oxford University Press, 2016, pp. 2318–34, doi:<a href=\"https://doi.org/10.1093/cercor/bhw090\">10.1093/cercor/bhw090</a>.","ama":"Booker S, Althof D, Gross A, et al. KCTD12 auxiliary proteins modulate kinetics of GABAB receptor-mediated inhibition in Cholecystokinin-containing interneurons. <i>Cerebral Cortex</i>. 2016;27(3):2318-2334. doi:<a href=\"https://doi.org/10.1093/cercor/bhw090\">10.1093/cercor/bhw090</a>"},"quality_controlled":"1","scopus_import":"1"},{"author":[{"orcid":"0000-0001-7429-7896","last_name":"Harada","id":"2E55CDF2-F248-11E8-B48F-1D18A9856A87","first_name":"Harumi","full_name":"Harada, Harumi"},{"full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto"}],"_id":"1094","quality_controlled":"1","citation":{"apa":"Harada, H., &#38; Shigemoto, R. (2016). Immunogold protein localization on grid-glued freeze-fracture replicas. In <i>High-Resolution Imaging of Cellular Proteins</i> (Vol. 1474, pp. 203–216). Springer. <a href=\"https://doi.org/10.1007/978-1-4939-6352-2_12\">https://doi.org/10.1007/978-1-4939-6352-2_12</a>","short":"H. Harada, R. Shigemoto, in:, High-Resolution Imaging of Cellular Proteins, Springer, 2016, pp. 203–216.","chicago":"Harada, Harumi, and Ryuichi Shigemoto. “Immunogold Protein Localization on Grid-Glued Freeze-Fracture Replicas.” In <i>High-Resolution Imaging of Cellular Proteins</i>, 1474:203–16. Springer, 2016. <a href=\"https://doi.org/10.1007/978-1-4939-6352-2_12\">https://doi.org/10.1007/978-1-4939-6352-2_12</a>.","ieee":"H. Harada and R. Shigemoto, “Immunogold protein localization on grid-glued freeze-fracture replicas,” in <i>High-Resolution Imaging of Cellular Proteins</i>, vol. 1474, Springer, 2016, pp. 203–216.","mla":"Harada, Harumi, and Ryuichi Shigemoto. “Immunogold Protein Localization on Grid-Glued Freeze-Fracture Replicas.” <i>High-Resolution Imaging of Cellular Proteins</i>, vol. 1474, Springer, 2016, pp. 203–16, doi:<a href=\"https://doi.org/10.1007/978-1-4939-6352-2_12\">10.1007/978-1-4939-6352-2_12</a>.","ista":"Harada H, Shigemoto R. 2016.Immunogold protein localization on grid-glued freeze-fracture replicas. In: High-Resolution Imaging of Cellular Proteins. Methods in Molecular Biology, vol. 1474, 203–216.","ama":"Harada H, Shigemoto R. Immunogold protein localization on grid-glued freeze-fracture replicas. In: <i>High-Resolution Imaging of Cellular Proteins</i>. Vol 1474. Springer; 2016:203-216. doi:<a href=\"https://doi.org/10.1007/978-1-4939-6352-2_12\">10.1007/978-1-4939-6352-2_12</a>"},"type":"book_chapter","intvolume":"      1474","publisher":"Springer","title":"Immunogold protein localization on grid-glued freeze-fracture replicas","volume":1474,"year":"2016","publication":"High-Resolution Imaging of Cellular Proteins","project":[{"grant_number":"604102","call_identifier":"FP7","_id":"25CD3DD2-B435-11E9-9278-68D0E5697425","name":"Localization of ion channels and receptors by two and three-dimensional immunoelectron microscopic approaches"}],"page":"203 - 216","publist_id":"6281","department":[{"_id":"RySh"}],"acknowledgement":"We thank Prof. Elek Molnár for providing us a pan-AMPAR anti-body used in Fig.2 and Dr. Ludek Lovicar for technical assistance in scanning electron microscope imaging. This work was supported by the European Union (HBP—Project Ref. 604102). ","date_created":"2018-12-11T11:50:06Z","article_processing_charge":"No","publication_identifier":{"issn":["0302-9743"],"eissn":["1611-3349"]},"acknowledged_ssus":[{"_id":"EM-Fac"}],"ec_funded":1,"language":[{"iso":"eng"}],"alternative_title":["Methods in Molecular Biology"],"date_updated":"2025-04-15T07:12:21Z","oa_version":"None","day":"12","date_published":"2016-08-12T00:00:00Z","status":"public","abstract":[{"text":"Immunogold labeling of freeze-fracture replicas has recently been used for high-resolution visualization of protein localization in electron microscopy. This method has higher labeling efficiency than conventional immunogold methods for membrane molecules allowing precise quantitative measurements. However, one of the limitations of freeze-fracture replica immunolabeling is difficulty in keeping structural orientation and identifying labeled profiles in complex tissues like brain. The difficulty is partly due to fragmentation of freeze-fracture replica preparations during labeling procedures and limited morphological clues on the replica surface. To overcome these issues, we introduce here a grid-glued replica method combined with SEM observation. This method allows histological staining before dissolving the tissue and easy handling of replicas during immunogold labeling, and keeps the whole replica surface intact without fragmentation. The procedure described here is also useful for matched double-replica analysis allowing further identification of labeled profiles in corresponding P-face and E-face.","lang":"eng"}],"publication_status":"published","doi":"10.1007/978-1-4939-6352-2_12","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","month":"08"},{"status":"public","year":"2016","publication":"Receptor and Ion Channel Detection in the Brain","title":"High-Resolution Localization of Membrane Proteins by SDS-Digested Freeze-Fracture Replica Labeling (SDS-FRL)","date_published":"2016-02-02T00:00:00Z","page":"233-245","publication_status":"published","abstract":[{"text":"Visualizing molecular localization at high resolution contributes to understanding of their functions and roles in physiological and pathological conditions. Sodium dodecyl sulfate-digested freeze-fracture replica labeling (SDS-FRL) is a powerful electron microscopy method to study high-resolution two-dimensional distribution of transmembrane proteins and their tightly associated proteins on platinum-carbon replica. During treatment with SDS, unfixed proteins and intracellular organelle are dissolved and integral membrane proteins captured and stabilized by carbon and platinum deposition are denatured, retaining most of their antigenicity, and exposed on exoplasmic and protoplasmic surfaces of lipid monolayers. The exposure of these antigens on the surface of replica facilitates the accessibility of antibodies and therefore provides 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 an additional procedure for fluorescence-guided electron microscopy for replica immunolabeling.","lang":"eng"}],"doi":"10.1007/978-1-4939-3064-7_17","department":[{"_id":"RySh"}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","publication_identifier":{"issn":["0893-2336"],"eissn":["1940-6045"],"eisbn":["9781493930647"],"isbn":["9781493930630"]},"acknowledgement":"We thank Mitsuru Ikeda for preparing replica images used in Fig. 2.","date_created":"2025-07-10T13:56:06Z","OA_type":"closed access","article_processing_charge":"No","month":"02","author":[{"first_name":"Harumi","orcid":"0000-0001-7429-7896","id":"2E55CDF2-F248-11E8-B48F-1D18A9856A87","last_name":"Harada","full_name":"Harada, Harumi"},{"full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto"}],"language":[{"iso":"eng"}],"_id":"19990","citation":{"mla":"Harada, Harumi, and Ryuichi Shigemoto. “High-Resolution Localization of Membrane Proteins by SDS-Digested Freeze-Fracture Replica Labeling (SDS-FRL).” <i>Receptor and Ion Channel Detection in the Brain</i>, Springer Nature, 2016, pp. 233–45, doi:<a href=\"https://doi.org/10.1007/978-1-4939-3064-7_17\">10.1007/978-1-4939-3064-7_17</a>.","ieee":"H. Harada and R. Shigemoto, “High-Resolution Localization of Membrane Proteins by SDS-Digested Freeze-Fracture Replica Labeling (SDS-FRL),” in <i>Receptor and Ion Channel Detection in the Brain</i>, Springer Nature, 2016, pp. 233–245.","ista":"Harada H, Shigemoto R. 2016.High-Resolution Localization of Membrane Proteins by SDS-Digested Freeze-Fracture Replica Labeling (SDS-FRL). In: Receptor and Ion Channel Detection in the Brain. , 233–245.","ama":"Harada H, Shigemoto R. High-Resolution Localization of Membrane Proteins by SDS-Digested Freeze-Fracture Replica Labeling (SDS-FRL). In: <i>Receptor and Ion Channel Detection in the Brain</i>. Neuromethods. Springer Nature; 2016:233-245. doi:<a href=\"https://doi.org/10.1007/978-1-4939-3064-7_17\">10.1007/978-1-4939-3064-7_17</a>","apa":"Harada, H., &#38; Shigemoto, R. (2016). High-Resolution Localization of Membrane Proteins by SDS-Digested Freeze-Fracture Replica Labeling (SDS-FRL). In <i>Receptor and Ion Channel Detection in the Brain</i> (pp. 233–245). Springer Nature. <a href=\"https://doi.org/10.1007/978-1-4939-3064-7_17\">https://doi.org/10.1007/978-1-4939-3064-7_17</a>","short":"H. Harada, R. Shigemoto, in:, Receptor and Ion Channel Detection in the Brain, Springer Nature, 2016, pp. 233–245.","chicago":"Harada, Harumi, and Ryuichi Shigemoto. “High-Resolution Localization of Membrane Proteins by SDS-Digested Freeze-Fracture Replica Labeling (SDS-FRL).” In <i>Receptor and Ion Channel Detection in the Brain</i>, 233–45. Neuromethods. Springer Nature, 2016. <a href=\"https://doi.org/10.1007/978-1-4939-3064-7_17\">https://doi.org/10.1007/978-1-4939-3064-7_17</a>."},"series_title":"Neuromethods","date_updated":"2026-04-07T08:32:03Z","quality_controlled":"1","oa_version":"None","type":"book_chapter","corr_author":"1","publisher":"Springer Nature","day":"02"},{"language":[{"iso":"eng"}],"oa":1,"issue":"1","oa_version":"Published Version","date_updated":"2025-09-23T09:38:39Z","file":[{"relation":"main_file","content_type":"application/pdf","access_level":"open_access","creator":"system","date_updated":"2020-07-14T12:45:01Z","file_size":3080111,"file_name":"IST-2016-482-v1+1_1-s2.0-S0896627314010472-main.pdf","checksum":"725f4d5be2dbb44b283ce722645ef37d","file_id":"5170","date_created":"2018-12-12T10:15:47Z"}],"day":"07","date_published":"2015-01-07T00:00:00Z","status":"public","publication_status":"published","abstract":[{"lang":"eng","text":"Synaptic efficacy and precision are influenced by the coupling of voltage-gated Ca2+ channels (VGCCs) to vesicles. But because the topography of VGCCs and their proximity to vesicles is unknown, a quantitative understanding of the determinants of vesicular release at nanometer scale is lacking. To investigate this, we combined freeze-fracture replica immunogold labeling of Cav2.1 channels, local [Ca2+] imaging, and patch pipette perfusion of EGTA at the calyx of Held. Between postnatal day 7 and 21, VGCCs formed variable sized clusters and vesicular release became less sensitive to EGTA, whereas fixed Ca2+ buffer properties remained constant. Experimentally constrained reaction-diffusion simulations suggest that Ca2+ sensors for vesicular release are located at the perimeter of VGCC clusters (&lt;30nm) and predict that VGCC number per cluster determines vesicular release probability without altering release time course. This &quot;perimeter release model&quot; provides a unifying framework accounting for developmental changes in both synaptic efficacy and time course."}],"ddc":["570"],"doi":"10.1016/j.neuron.2014.11.019","pmid":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/3.0/legalcode","name":"Creative Commons Attribution 3.0 Unported (CC BY 3.0)","image":"/images/cc_by.png","short":"CC BY (3.0)"},"month":"01","OA_type":"hybrid","author":[{"full_name":"Nakamura, Yukihiro","first_name":"Yukihiro","last_name":"Nakamura"},{"last_name":"Harada","id":"2E55CDF2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7429-7896","first_name":"Harumi","full_name":"Harada, Harumi"},{"full_name":"Kamasawa, Naomi","first_name":"Naomi","last_name":"Kamasawa"},{"first_name":"Ko","last_name":"Matsui","full_name":"Matsui, Ko"},{"full_name":"Rothman, Jason","last_name":"Rothman","first_name":"Jason"},{"full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444"},{"full_name":"Silver, R Angus","last_name":"Silver","first_name":"R Angus"},{"first_name":"David","last_name":"Digregorio","full_name":"Digregorio, David"},{"first_name":"Tomoyuki","last_name":"Takahashi","full_name":"Takahashi, Tomoyuki"}],"_id":"1546","file_date_updated":"2020-07-14T12:45:01Z","has_accepted_license":"1","scopus_import":"1","quality_controlled":"1","citation":{"chicago":"Nakamura, Yukihiro, Harumi Harada, Naomi Kamasawa, Ko Matsui, Jason Rothman, Ryuichi Shigemoto, R Angus Silver, David Digregorio, and Tomoyuki Takahashi. “Nanoscale Distribution of Presynaptic Ca2+ Channels and Its Impact on Vesicular Release during Development.” <i>Neuron</i>. Elsevier, 2015. <a href=\"https://doi.org/10.1016/j.neuron.2014.11.019\">https://doi.org/10.1016/j.neuron.2014.11.019</a>.","apa":"Nakamura, Y., Harada, H., Kamasawa, N., Matsui, K., Rothman, J., Shigemoto, R., … Takahashi, T. (2015). Nanoscale distribution of presynaptic Ca2+ channels and its impact on vesicular release during development. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2014.11.019\">https://doi.org/10.1016/j.neuron.2014.11.019</a>","short":"Y. Nakamura, H. Harada, N. Kamasawa, K. Matsui, J. Rothman, R. Shigemoto, R.A. Silver, D. Digregorio, T. Takahashi, Neuron 85 (2015) 145–158.","ama":"Nakamura Y, Harada H, Kamasawa N, et al. Nanoscale distribution of presynaptic Ca2+ channels and its impact on vesicular release during development. <i>Neuron</i>. 2015;85(1):145-158. doi:<a href=\"https://doi.org/10.1016/j.neuron.2014.11.019\">10.1016/j.neuron.2014.11.019</a>","ista":"Nakamura Y, Harada H, Kamasawa N, Matsui K, Rothman J, Shigemoto R, Silver RA, Digregorio D, Takahashi T. 2015. Nanoscale distribution of presynaptic Ca2+ channels and its impact on vesicular release during development. Neuron. 85(1), 145–158.","mla":"Nakamura, Yukihiro, et al. “Nanoscale Distribution of Presynaptic Ca2+ Channels and Its Impact on Vesicular Release during Development.” <i>Neuron</i>, vol. 85, no. 1, Elsevier, 2015, pp. 145–58, doi:<a href=\"https://doi.org/10.1016/j.neuron.2014.11.019\">10.1016/j.neuron.2014.11.019</a>.","ieee":"Y. Nakamura <i>et al.</i>, “Nanoscale distribution of presynaptic Ca2+ channels and its impact on vesicular release during development,” <i>Neuron</i>, vol. 85, no. 1. Elsevier, pp. 145–158, 2015."},"type":"journal_article","isi":1,"intvolume":"        85","publisher":"Elsevier","title":"Nanoscale distribution of presynaptic Ca2+ channels and its impact on vesicular release during development","article_type":"original","external_id":{"isi":["000348295100015"],"pmid":["25533484"]},"volume":85,"year":"2015","publication":"Neuron","pubrep_id":"482","page":"145 - 158","OA_place":"publisher","publist_id":"5625","department":[{"_id":"RySh"}],"date_created":"2018-12-11T11:52:39Z","acknowledgement":"This work was supported by the Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Agency to T.T. and R.S.; by the funding provided by Okinawa Institute of Science and Technology (OIST) to T.T. and Y.N.; by JSPS Core-to-Core Program, A. Advanced Networks to T.T.; by the Grant-in-Aid for Young Scientists from the Japanese Ministry of Education, Culture, Sports, Science and Technology (#23700474) to Y.N.; by the Centre National de la Recherche Scientifique through the Actions Thematiques et Initatives sur Programme, Fondation Fyssen, Fondation pour la Recherche Medicale, Federation pour la Recherche sur le Cerveau, Agence Nationale de la Recherche (ANR-2007-Neuro-008-01 and ANR-2010-BLAN-1411-01) to D.D. and Y.N.; and by the European Commission Coordination Action ENINET (LSHM-CT-2005-19063) to D.D. and R.A.S. R.A.S. and J.S.R. were funded by Wellcome Trust Senior (064413) and Principal (095667) Research Fellowship and an ERC advance grant (294667) to RAS.","article_processing_charge":"Yes (in subscription journal)","publication_identifier":{"eissn":["1097-4199"],"issn":["0896-6273"]}},{"month":"09","doi":"10.1002/cne.23774","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","abstract":[{"lang":"eng","text":"γ-Aminobutyric acid (GABA)- and glycine-mediated hyperpolarizing inhibition is associated with a chloride influx that depends on the inwardly directed chloride electrochemical gradient. In neurons, the extrusion of chloride from the cytosol primarily depends on the expression of an isoform of potassium-chloride cotransporters (KCC2s). KCC2 is crucial in the regulation of the inhibitory tone of neural circuits, including pain processing neural assemblies. Thus we investigated the cellular distribution of KCC2 in neurons underlying pain processing in the superficial spinal dorsal horn of rats by using high-resolution immunocytochemical methods. We demonstrated that perikarya and dendrites widely expressed KCC2, but axon terminals proved to be negative for KCC2. In single ultrathin sections, silver deposits labeling KCC2 molecules showed different densities on the surface of dendritic profiles, some of which were negative for KCC2. In freeze fracture replicas and tissue sections double stained for the β3-subunit of GABAA receptors and KCC2, GABAA receptors were revealed on dendritic segments with high and also with low KCC2 densities. By measuring the distances between spots immunoreactive for gephyrin (a scaffolding protein of GABAA and glycine receptors) and KCC2 on the surface of neurokinin 1 (NK1) receptor-immunoreactive dendrites, we found that gephyrin-immunoreactive spots were located at various distances from KCC2 cotransporters; 5.7 % of them were recovered in the middle of 4-10-μm-long dendritic segments that were free of KCC2 immunostaining. The variable local densities of KCC2 may result in variable postsynaptic potentials evoked by the activation of GABAA and glycine receptors along the dendrites of spinal neurons."}],"publication_status":"published","date_published":"2015-09-01T00:00:00Z","status":"public","day":"01","issue":"13","oa_version":"None","date_updated":"2025-09-23T08:26:48Z","language":[{"iso":"eng"}],"date_created":"2018-12-11T11:52:42Z","acknowledgement":"Funded by:\r\nHungarian Academy of Sciences. Grant Number: MTA-TKI 242\r\nHungarian Brain Research Program. Grant Number: KTIA_NAP_13-1-2013-0001\r\nSolution Oriented Research for Science and Technology from the Japan Science and Technology Agency Japanese Ministry of Education, Culture, Sports, Science and Technology","article_processing_charge":"No","department":[{"_id":"RySh"}],"page":"1967 - 1983","publist_id":"5614","external_id":{"isi":["000358228700006"]},"title":"Differential expression patterns of K+Cl- cotransporter 2 in neurons within the superficial spinal dorsal horn of rats","volume":523,"year":"2015","publication":"Journal of Comparative Neurology","intvolume":"       523","publisher":"Wiley-Blackwell","type":"journal_article","isi":1,"quality_controlled":"1","scopus_import":"1","citation":{"ama":"Javdani F, Holló K, Hegedűs K, et al. Differential expression patterns of K+Cl- cotransporter 2 in neurons within the superficial spinal dorsal horn of rats. <i>Journal of Comparative Neurology</i>. 2015;523(13):1967-1983. doi:<a href=\"https://doi.org/10.1002/cne.23774\">10.1002/cne.23774</a>","ieee":"F. Javdani <i>et al.</i>, “Differential expression patterns of K+Cl- cotransporter 2 in neurons within the superficial spinal dorsal horn of rats,” <i>Journal of Comparative Neurology</i>, vol. 523, no. 13. Wiley-Blackwell, pp. 1967–1983, 2015.","mla":"Javdani, Fariba, et al. “Differential Expression Patterns of K+Cl- Cotransporter 2 in Neurons within the Superficial Spinal Dorsal Horn of Rats.” <i>Journal of Comparative Neurology</i>, vol. 523, no. 13, Wiley-Blackwell, 2015, pp. 1967–83, doi:<a href=\"https://doi.org/10.1002/cne.23774\">10.1002/cne.23774</a>.","ista":"Javdani F, Holló K, Hegedűs K, Kis G, Hegyi Z, Dócs K, Kasugai Y, Fukazawa Y, Shigemoto R, Antal M. 2015. Differential expression patterns of K+Cl- cotransporter 2 in neurons within the superficial spinal dorsal horn of rats. Journal of Comparative Neurology. 523(13), 1967–1983.","chicago":"Javdani, Fariba, Krisztina Holló, Krisztina Hegedűs, Gréta Kis, Zoltán Hegyi, Klaudia Dócs, Yu Kasugai, Yugo Fukazawa, Ryuichi Shigemoto, and Miklós Antal. “Differential Expression Patterns of K+Cl- Cotransporter 2 in Neurons within the Superficial Spinal Dorsal Horn of Rats.” <i>Journal of Comparative Neurology</i>. Wiley-Blackwell, 2015. <a href=\"https://doi.org/10.1002/cne.23774\">https://doi.org/10.1002/cne.23774</a>.","short":"F. Javdani, K. Holló, K. Hegedűs, G. Kis, Z. Hegyi, K. Dócs, Y. Kasugai, Y. Fukazawa, R. Shigemoto, M. Antal, Journal of Comparative Neurology 523 (2015) 1967–1983.","apa":"Javdani, F., Holló, K., Hegedűs, K., Kis, G., Hegyi, Z., Dócs, K., … Antal, M. (2015). Differential expression patterns of K+Cl- cotransporter 2 in neurons within the superficial spinal dorsal horn of rats. <i>Journal of Comparative Neurology</i>. Wiley-Blackwell. <a href=\"https://doi.org/10.1002/cne.23774\">https://doi.org/10.1002/cne.23774</a>"},"author":[{"first_name":"Fariba","last_name":"Javdani","full_name":"Javdani, Fariba"},{"full_name":"Holló, Krisztina","first_name":"Krisztina","last_name":"Holló"},{"full_name":"Hegedűs, Krisztina","last_name":"Hegedűs","first_name":"Krisztina"},{"full_name":"Kis, Gréta","first_name":"Gréta","last_name":"Kis"},{"last_name":"Hegyi","first_name":"Zoltán","full_name":"Hegyi, Zoltán"},{"first_name":"Klaudia","last_name":"Dócs","full_name":"Dócs, Klaudia"},{"last_name":"Kasugai","first_name":"Yu","full_name":"Kasugai, Yu"},{"full_name":"Fukazawa, Yugo","last_name":"Fukazawa","first_name":"Yugo"},{"first_name":"Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi"},{"first_name":"Miklós","last_name":"Antal","full_name":"Antal, Miklós"}],"_id":"1557"},{"type":"journal_article","isi":1,"publisher":"Society for Neuroscience","intvolume":"        34","author":[{"full_name":"Matsukawa, Hiroshi","first_name":"Hiroshi","last_name":"Matsukawa"},{"full_name":"Akiyoshi Nishimura, Sachiko","last_name":"Akiyoshi Nishimura","first_name":"Sachiko"},{"full_name":"Zhang, Qi","first_name":"Qi","last_name":"Zhang"},{"last_name":"Luján","first_name":"Rafael","full_name":"Luján, Rafael"},{"full_name":"Yamaguchi, Kazuhiko","last_name":"Yamaguchi","first_name":"Kazuhiko"},{"full_name":"Goto, Hiromichi","first_name":"Hiromichi","last_name":"Goto"},{"full_name":"Yaguchi, Kunio","last_name":"Yaguchi","first_name":"Kunio"},{"first_name":"Tsutomu","last_name":"Hashikawa","full_name":"Hashikawa, Tsutomu"},{"last_name":"Sano","first_name":"Chie","full_name":"Sano, Chie"},{"full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto"},{"full_name":"Nakashiba, Toshiaki","last_name":"Nakashiba","first_name":"Toshiaki"},{"full_name":"Itohara, Shigeyoshi","first_name":"Shigeyoshi","last_name":"Itohara"}],"_id":"2018","file_date_updated":"2022-05-24T08:41:41Z","citation":{"ista":"Matsukawa H, Akiyoshi Nishimura S, Zhang Q, Luján R, Yamaguchi K, Goto H, Yaguchi K, Hashikawa T, Sano C, Shigemoto R, Nakashiba T, Itohara S. 2014. Netrin-G/NGL complexes encode functional synaptic diversification. Journal of Neuroscience. 34(47), 15779–15792.","ieee":"H. Matsukawa <i>et al.</i>, “Netrin-G/NGL complexes encode functional synaptic diversification,” <i>Journal of Neuroscience</i>, vol. 34, no. 47. Society for Neuroscience, pp. 15779–15792, 2014.","mla":"Matsukawa, Hiroshi, et al. “Netrin-G/NGL Complexes Encode Functional Synaptic Diversification.” <i>Journal of Neuroscience</i>, vol. 34, no. 47, Society for Neuroscience, 2014, pp. 15779–92, doi:<a href=\"https://doi.org/10.1523/JNEUROSCI.1141-14.2014\">10.1523/JNEUROSCI.1141-14.2014</a>.","ama":"Matsukawa H, Akiyoshi Nishimura S, Zhang Q, et al. Netrin-G/NGL complexes encode functional synaptic diversification. <i>Journal of Neuroscience</i>. 2014;34(47):15779-15792. doi:<a href=\"https://doi.org/10.1523/JNEUROSCI.1141-14.2014\">10.1523/JNEUROSCI.1141-14.2014</a>","short":"H. Matsukawa, S. Akiyoshi Nishimura, Q. Zhang, R. Luján, K. Yamaguchi, H. Goto, K. Yaguchi, T. Hashikawa, C. Sano, R. Shigemoto, T. Nakashiba, S. Itohara, Journal of Neuroscience 34 (2014) 15779–15792.","apa":"Matsukawa, H., Akiyoshi Nishimura, S., Zhang, Q., Luján, R., Yamaguchi, K., Goto, H., … Itohara, S. (2014). Netrin-G/NGL complexes encode functional synaptic diversification. <i>Journal of Neuroscience</i>. Society for Neuroscience. <a href=\"https://doi.org/10.1523/JNEUROSCI.1141-14.2014\">https://doi.org/10.1523/JNEUROSCI.1141-14.2014</a>","chicago":"Matsukawa, Hiroshi, Sachiko Akiyoshi Nishimura, Qi Zhang, Rafael Luján, Kazuhiko Yamaguchi, Hiromichi Goto, Kunio Yaguchi, et al. “Netrin-G/NGL Complexes Encode Functional Synaptic Diversification.” <i>Journal of Neuroscience</i>. Society for Neuroscience, 2014. <a href=\"https://doi.org/10.1523/JNEUROSCI.1141-14.2014\">https://doi.org/10.1523/JNEUROSCI.1141-14.2014</a>."},"has_accepted_license":"1","scopus_import":"1","quality_controlled":"1","department":[{"_id":"RySh"}],"publication_identifier":{"eissn":["1529-2401"],"issn":["0270-6474"]},"date_created":"2018-12-11T11:55:14Z","acknowledgement":"This work was supported by “Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program)” initiated by the Council for Science and Technology Policy.","article_processing_charge":"No","year":"2014","publication":"Journal of Neuroscience","external_id":{"pmid":["25411505"],"isi":["000345907500026"]},"title":"Netrin-G/NGL complexes encode functional synaptic diversification","article_type":"original","volume":34,"page":"15779 - 15792","publist_id":"5054","file":[{"date_updated":"2022-05-24T08:41:41Z","creator":"dernst","access_level":"open_access","content_type":"application/pdf","relation":"main_file","date_created":"2022-05-24T08:41:41Z","file_id":"11410","checksum":"6913e9bc26e9fc1c0441a739a4199229","success":1,"file_size":3963728,"file_name":"2014_JournNeuroscience_Matsukawa.pdf"}],"day":"19","language":[{"iso":"eng"}],"oa":1,"issue":"47","date_updated":"2025-09-29T12:00:37Z","oa_version":"Published Version","doi":"10.1523/JNEUROSCI.1141-14.2014","pmid":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","month":"11","status":"public","date_published":"2014-11-19T00:00:00Z","publication_status":"published","abstract":[{"text":"Synaptic cell adhesion molecules are increasingly gaining attention for conferring specific properties to individual synapses. Netrin-G1 and netrin-G2 are trans-synaptic adhesion molecules that distribute on distinct axons, and their presence restricts the expression of their cognate receptors, NGL1 and NGL2, respectively, to specific subdendritic segments of target neurons. However, the neural circuits and functional roles of netrin-G isoform complexes remain unclear. Here, we use netrin-G-KO and NGL-KO mice to reveal that netrin-G1/NGL1 and netrin-G2/NGL2 interactions specify excitatory synapses in independent hippocampal pathways. In the hippocampal CA1 area, netrin-G1/NGL1 and netrin-G2/NGL2 were expressed in the temporoammonic and Schaffer collateral pathways, respectively. The lack of presynaptic netrin-Gs led to the dispersion of NGLs from postsynaptic membranes. In accord, netrin-G mutant synapses displayed opposing phenotypes in long-term and short-term plasticity through discrete biochemical pathways. The plasticity phenotypes in netrin-G-KOs were phenocopied in NGL-KOs, with a corresponding loss of netrin-Gs from presynaptic membranes. Our findings show that netrin-G/NGL interactions differentially control synaptic plasticity in distinct circuits via retrograde signaling mechanisms and explain how synaptic inputs are diversified to control neuronal activity.","lang":"eng"}],"ddc":["570"]},{"publication_status":"published","abstract":[{"text":"We examined the synaptic structure, quantity, and distribution of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)- and N-methyl-D-aspartate (NMDA)-type glutamate receptors (AMPARs and NMDARs, respectively) in rat cochlear nuclei by a highly sensitive freeze-fracture replica labeling technique. Four excitatory synapses formed by two distinct inputs, auditory nerve (AN) and parallel fibers (PF), on different cell types were analyzed. These excitatory synapse types included AN synapses on bushy cells (AN-BC synapses) and fusiform cells (AN-FC synapses) and PF synapses on FC (PF-FC synapses) and cartwheel cell spines (PF-CwC synapses). Immunogold labeling revealed differences in synaptic structure as well as AMPAR and NMDAR number and/or density in both AN and PF synapses, indicating a target-dependent organization. The immunogold receptor labeling also identified differences in the synaptic organization of FCs based on AN or PF connections, indicating an input-dependent organization in FCs. Among the four excitatory synapse types, the AN-BC synapses were the smallest and had the most densely packed intramembrane particles (IMPs), whereas the PF-CwC synapses were the largest and had sparsely packed IMPs. All four synapse types showed positive correlations between the IMP-cluster area and the AMPAR number, indicating a common intrasynapse-type relationship for glutamatergic synapses. Immunogold particles for AMPARs were distributed over the entire area of individual AN synapses; PF synapses often showed synaptic areas devoid of labeling. The gold-labeling for NMDARs occurred in a mosaic fashion, with less positive correlations between the IMP-cluster area and the NMDAR number. Our observations reveal target- and input-dependent features in the structure, number, and organization of AMPARs and NMDARs in AN and PF synapses.","lang":"eng"}],"date_published":"2014-07-29T00:00:00Z","status":"public","month":"07","main_file_link":[{"url":"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198489/","open_access":"1"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","doi":"10.1002/cne.23654","oa_version":"Submitted Version","date_updated":"2025-09-29T11:47:23Z","issue":"18","oa":1,"language":[{"iso":"eng"}],"day":"29","publist_id":"4974","page":"4023 - 4042","volume":522,"title":"Target- and input-dependent organization of AMPA and NMDA receptors in synaptic connections of the cochlear nucleus","external_id":{"isi":["000343973100005"]},"publication":"Journal of Comparative Neurology","year":"2014","article_processing_charge":"No","date_created":"2018-12-11T11:55:30Z","acknowledgement":"National Institutes of Health (NIH) Grant Number: 1R01DC013048‐0; Biotechnology and Biological Sciences Research Council, UK Grant Number: BB/J015938/1\r\n","department":[{"_id":"RySh"}],"quality_controlled":"1","scopus_import":"1","citation":{"short":"M. Rubio, Y. Fukazawa, N. Kamasawa, C. Clarkson, E. Molnár, R. Shigemoto, Journal of Comparative Neurology 522 (2014) 4023–4042.","apa":"Rubio, M., Fukazawa, Y., Kamasawa, N., Clarkson, C., Molnár, E., &#38; Shigemoto, R. (2014). Target- and input-dependent organization of AMPA and NMDA receptors in synaptic connections of the cochlear nucleus. <i>Journal of Comparative Neurology</i>. Wiley-Blackwell. <a href=\"https://doi.org/10.1002/cne.23654\">https://doi.org/10.1002/cne.23654</a>","chicago":"Rubio, Maía, Yugo Fukazawa, Naomi Kamasawa, Cheryl Clarkson, Elek Molnár, and Ryuichi Shigemoto. “Target- and Input-Dependent Organization of AMPA and NMDA Receptors in Synaptic Connections of the Cochlear Nucleus.” <i>Journal of Comparative Neurology</i>. Wiley-Blackwell, 2014. <a href=\"https://doi.org/10.1002/cne.23654\">https://doi.org/10.1002/cne.23654</a>.","ieee":"M. Rubio, Y. Fukazawa, N. Kamasawa, C. Clarkson, E. Molnár, and R. Shigemoto, “Target- and input-dependent organization of AMPA and NMDA receptors in synaptic connections of the cochlear nucleus,” <i>Journal of Comparative Neurology</i>, vol. 522, no. 18. Wiley-Blackwell, pp. 4023–4042, 2014.","mla":"Rubio, Maía, et al. “Target- and Input-Dependent Organization of AMPA and NMDA Receptors in Synaptic Connections of the Cochlear Nucleus.” <i>Journal of Comparative Neurology</i>, vol. 522, no. 18, Wiley-Blackwell, 2014, pp. 4023–42, doi:<a href=\"https://doi.org/10.1002/cne.23654\">10.1002/cne.23654</a>.","ista":"Rubio M, Fukazawa Y, Kamasawa N, Clarkson C, Molnár E, Shigemoto R. 2014. Target- and input-dependent organization of AMPA and NMDA receptors in synaptic connections of the cochlear nucleus. Journal of Comparative Neurology. 522(18), 4023–4042.","ama":"Rubio M, Fukazawa Y, Kamasawa N, Clarkson C, Molnár E, Shigemoto R. Target- and input-dependent organization of AMPA and NMDA receptors in synaptic connections of the cochlear nucleus. <i>Journal of Comparative Neurology</i>. 2014;522(18):4023-4042. doi:<a href=\"https://doi.org/10.1002/cne.23654\">10.1002/cne.23654</a>"},"_id":"2064","author":[{"first_name":"Maía","last_name":"Rubio","full_name":"Rubio, Maía"},{"full_name":"Fukazawa, Yugo","first_name":"Yugo","last_name":"Fukazawa"},{"last_name":"Kamasawa","first_name":"Naomi","full_name":"Kamasawa, Naomi"},{"full_name":"Clarkson, Cheryl","first_name":"Cheryl","last_name":"Clarkson"},{"first_name":"Elek","last_name":"Molnár","full_name":"Molnár, Elek"},{"full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto","orcid":"0000-0001-8761-9444"}],"intvolume":"       522","publisher":"Wiley-Blackwell","isi":1,"type":"journal_article"},{"department":[{"_id":"RySh"}],"article_processing_charge":"No","acknowledgement":"This work was supported in part by a Grant-in-Aid for Scientific Research on Innovative Areas (Comprehensive Brain Science Network) and (B) 17330153, from the Ministry of Education, Culture, Sports, Science and Technology of Japan.","date_created":"2018-12-11T11:54:35Z","publication":"PLoS One","year":"2014","volume":9,"external_id":{"isi":["000343671700028"]},"title":"Functional deficiency of MHC class i enhances LTP and abolishes LTD in the nucleus accumbens of mice","publist_id":"5200","pubrep_id":"439","isi":1,"type":"journal_article","publisher":"Public Library of Science","intvolume":"         9","_id":"1895","file_date_updated":"2020-07-14T12:45:20Z","author":[{"full_name":"Edamura, Mitsuhiro","first_name":"Mitsuhiro","last_name":"Edamura"},{"first_name":"Gen","last_name":"Murakami","full_name":"Murakami, Gen"},{"last_name":"Meng","first_name":"Hongrui","full_name":"Meng, Hongrui"},{"full_name":"Itakura, Makoto","first_name":"Makoto","last_name":"Itakura"},{"first_name":"Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi"},{"full_name":"Fukuda, Atsuo","first_name":"Atsuo","last_name":"Fukuda"},{"full_name":"Nakahara, Daiichiro","last_name":"Nakahara","first_name":"Daiichiro"}],"citation":{"chicago":"Edamura, Mitsuhiro, Gen Murakami, Hongrui Meng, Makoto Itakura, Ryuichi Shigemoto, Atsuo Fukuda, and Daiichiro Nakahara. “Functional Deficiency of MHC Class i Enhances LTP and Abolishes LTD in the Nucleus Accumbens of Mice.” <i>PLoS One</i>. Public Library of Science, 2014. <a href=\"https://doi.org/10.1371/journal.pone.0107099\">https://doi.org/10.1371/journal.pone.0107099</a>.","short":"M. Edamura, G. Murakami, H. Meng, M. Itakura, R. Shigemoto, A. Fukuda, D. Nakahara, PLoS One 9 (2014).","apa":"Edamura, M., Murakami, G., Meng, H., Itakura, M., Shigemoto, R., Fukuda, A., &#38; Nakahara, D. (2014). Functional deficiency of MHC class i enhances LTP and abolishes LTD in the nucleus accumbens of mice. <i>PLoS One</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pone.0107099\">https://doi.org/10.1371/journal.pone.0107099</a>","ama":"Edamura M, Murakami G, Meng H, et al. Functional deficiency of MHC class i enhances LTP and abolishes LTD in the nucleus accumbens of mice. <i>PLoS One</i>. 2014;9(9). doi:<a href=\"https://doi.org/10.1371/journal.pone.0107099\">10.1371/journal.pone.0107099</a>","ieee":"M. Edamura <i>et al.</i>, “Functional deficiency of MHC class i enhances LTP and abolishes LTD in the nucleus accumbens of mice,” <i>PLoS One</i>, vol. 9, no. 9. Public Library of Science, 2014.","mla":"Edamura, Mitsuhiro, et al. “Functional Deficiency of MHC Class i Enhances LTP and Abolishes LTD in the Nucleus Accumbens of Mice.” <i>PLoS One</i>, vol. 9, no. 9, e107099, Public Library of Science, 2014, doi:<a href=\"https://doi.org/10.1371/journal.pone.0107099\">10.1371/journal.pone.0107099</a>.","ista":"Edamura M, Murakami G, Meng H, Itakura M, Shigemoto R, Fukuda A, Nakahara D. 2014. Functional deficiency of MHC class i enhances LTP and abolishes LTD in the nucleus accumbens of mice. PLoS One. 9(9), e107099."},"article_number":"e107099","scopus_import":"1","has_accepted_license":"1","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","doi":"10.1371/journal.pone.0107099","month":"09","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"status":"public","date_published":"2014-09-30T00:00:00Z","ddc":["570"],"publication_status":"published","abstract":[{"lang":"eng","text":"Major histocompatibility complex class I (MHCI) molecules were recently identified as novel regulators of synaptic plasticity. These molecules are expressed in various brain areas, especially in regions undergoing activity-dependent synaptic plasticity, but their role in the nucleus accumbens (NAc) is unknown. In this study, we investigated the effects of genetic disruption of MHCI function, through deletion of β2-microblobulin, which causes lack of cell surface expression of MHCI. First, we confirmed that MHCI molecules are expressed in the NAc core in wild-type mice. Second, we performed electrophysiological recordings with NAc core slices from wild-type and β2-microglobulin knock-out mice lacking cell surface expression of MHCI. We found that low frequency stimulation induced long-term depression in wild-type but not knock-out mice, whereas high frequency stimulation induced long-term potentiation in both genotypes, with a larger magnitude in knock-out mice. Furthermore, we demonstrated that knock-out mice showed more persistent behavioral sensitization to cocaine, which is a NAc-related behavior. Using this model, we analyzed the density of total AMPA receptors and their subunits GluR1 and GluR2 in the NAc core, by SDS-digested freeze-fracture replica labeling. After repeated cocaine exposure, the density of GluR1 was increased, but there was no change in total AMPA receptors and GluR2 levels in wildtype mice. In contrast, following repeated cocaine exposure, increased densities of total AMPA receptors, GluR1 and GluR2 were observed in knock-out mice. These results indicate that functional deficiency of MHCI enhances synaptic potentiation, induced by electrical and pharmacological stimulation."}],"file":[{"content_type":"application/pdf","relation":"main_file","date_updated":"2020-07-14T12:45:20Z","creator":"system","access_level":"open_access","file_name":"IST-2016-439-v1+1_journal.pone.0107099.pdf","file_size":6262085,"date_created":"2018-12-12T10:09:01Z","file_id":"4724","checksum":"1f3be936be93114596d61ba44cacee69"}],"day":"30","oa":1,"language":[{"iso":"eng"}],"oa_version":"Published Version","date_updated":"2025-09-29T13:04:38Z","issue":"9"},{"publisher":"Elsevier","intvolume":"        84","type":"journal_article","isi":1,"citation":{"ama":"Ritzau Jost A, Delvendahl I, Rings A, et al. Ultrafast action potentials mediate kilohertz signaling at a central synapse. <i>Neuron</i>. 2014;84(1):152-163. doi:<a href=\"https://doi.org/10.1016/j.neuron.2014.08.036\">10.1016/j.neuron.2014.08.036</a>","ieee":"A. Ritzau Jost <i>et al.</i>, “Ultrafast action potentials mediate kilohertz signaling at a central synapse,” <i>Neuron</i>, vol. 84, no. 1. Elsevier, pp. 152–163, 2014.","ista":"Ritzau Jost A, Delvendahl I, Rings A, Byczkowicz N, Harada H, Shigemoto R, Hirrlinger J, Eilers J, Hallermann S. 2014. Ultrafast action potentials mediate kilohertz signaling at a central synapse. Neuron. 84(1), 152–163.","mla":"Ritzau Jost, Andreas, et al. “Ultrafast Action Potentials Mediate Kilohertz Signaling at a Central Synapse.” <i>Neuron</i>, vol. 84, no. 1, Elsevier, 2014, pp. 152–63, doi:<a href=\"https://doi.org/10.1016/j.neuron.2014.08.036\">10.1016/j.neuron.2014.08.036</a>.","chicago":"Ritzau Jost, Andreas, Igor Delvendahl, Annika Rings, Niklas Byczkowicz, Harumi Harada, Ryuichi Shigemoto, Johannes Hirrlinger, Jens Eilers, and Stefan Hallermann. “Ultrafast Action Potentials Mediate Kilohertz Signaling at a Central Synapse.” <i>Neuron</i>. Elsevier, 2014. <a href=\"https://doi.org/10.1016/j.neuron.2014.08.036\">https://doi.org/10.1016/j.neuron.2014.08.036</a>.","short":"A. Ritzau Jost, I. Delvendahl, A. Rings, N. Byczkowicz, H. Harada, R. Shigemoto, J. Hirrlinger, J. Eilers, S. Hallermann, Neuron 84 (2014) 152–163.","apa":"Ritzau Jost, A., Delvendahl, I., Rings, A., Byczkowicz, N., Harada, H., Shigemoto, R., … Hallermann, S. (2014). Ultrafast action potentials mediate kilohertz signaling at a central synapse. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2014.08.036\">https://doi.org/10.1016/j.neuron.2014.08.036</a>"},"quality_controlled":"1","scopus_import":"1","author":[{"first_name":"Andreas","last_name":"Ritzau Jost","full_name":"Ritzau Jost, Andreas"},{"last_name":"Delvendahl","first_name":"Igor","full_name":"Delvendahl, Igor"},{"last_name":"Rings","first_name":"Annika","full_name":"Rings, Annika"},{"full_name":"Byczkowicz, Niklas","last_name":"Byczkowicz","first_name":"Niklas"},{"first_name":"Harumi","orcid":"0000-0001-7429-7896","id":"2E55CDF2-F248-11E8-B48F-1D18A9856A87","last_name":"Harada","full_name":"Harada, Harumi"},{"full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto","first_name":"Ryuichi"},{"first_name":"Johannes","last_name":"Hirrlinger","full_name":"Hirrlinger, Johannes"},{"last_name":"Eilers","first_name":"Jens","full_name":"Eilers, Jens"},{"first_name":"Stefan","last_name":"Hallermann","full_name":"Hallermann, Stefan"}],"_id":"1898","date_created":"2018-12-11T11:54:36Z","article_processing_charge":"No","department":[{"_id":"RySh"}],"page":"152 - 163","publist_id":"5197","year":"2014","publication":"Neuron","title":"Ultrafast action potentials mediate kilohertz signaling at a central synapse","external_id":{"isi":["000342502800017"]},"volume":84,"day":"01","issue":"1","date_updated":"2025-09-29T13:03:03Z","oa_version":"None","language":[{"iso":"eng"}],"month":"10","doi":"10.1016/j.neuron.2014.08.036","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","abstract":[{"lang":"eng","text":"Fast synaptic transmission is important for rapid information processing. To explore the maximal rate of neuronal signaling and to analyze the presynaptic mechanisms, we focused on the input layer of the cerebellar cortex, where exceptionally high action potential (AP) frequencies have been reported invivo. With paired recordings between presynaptic cerebellar mossy fiber boutons and postsynaptic granule cells, we demonstrate reliable neurotransmission upto ~1 kHz. Presynaptic APs are ultrafast, with ~100μs half-duration. Both Kv1 and Kv3 potassium channels mediate the fast repolarization, rapidly inactivating sodium channels ensure metabolic efficiency, and little AP broadening occurs during bursts of up to 1.5 kHz. Presynaptic Cav2.1 (P/Q-type) calcium channels open efficiently during ultrafast APs. Furthermore, a subset of synaptic vesicles is tightly coupled to Ca2+ channels, and vesicles are rapidly recruited to the release site. These data reveal mechanisms of presynaptic AP generation and transmitter release underlying neuronal kHz signaling."}],"publication_status":"published","status":"public","date_published":"2014-10-01T00:00:00Z"},{"issue":"1","date_updated":"2025-09-29T12:19:01Z","oa_version":"Submitted Version","oa":1,"language":[{"iso":"eng"}],"day":"07","corr_author":"1","publication_status":"published","abstract":[{"lang":"eng","text":"Long-lasting memories are formed when the stimulus is temporally distributed (spacing effect). However, the synaptic mechanisms underlying this robust phenomenon and the precise time course of the synaptic modifications that occur during learning remain unclear. Here we examined the adaptation of horizontal optokinetic response in mice that underwent 1 h of massed and spaced training at varying intervals. Despite similar acquisition by all training protocols, 1 h of spacing produced the highest memory retention at 24 h, which lasted for 1 mo. The distinct kinetics of memory are strongly correlated with the reduction of floccular parallel fiber-Purkinje cell synapses but not with AMPA receptor (AMPAR) number and synapse size. After the spaced training, we observed 25%, 23%, and 12% reduction in AMPAR density, synapse size, and synapse number, respectively. Four hours after the spaced training, half of the synapses and Purkinje cell spines had been eliminated, whereas AMPAR density and synapse size were recovered in remaining synapses. Surprisingly, massed training also produced long-term memory and halving of synapses; however, this occurred slowly over days, and the memory lasted for only 1 wk. This distinct kinetics of structural plasticity may serve as a basis for unique temporal profiles in the formation and decay of memory with or without intervals."}],"status":"public","date_published":"2014-01-07T00:00:00Z","main_file_link":[{"open_access":"1","url":"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890840/"}],"month":"01","doi":"10.1073/pnas.1303317110","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","citation":{"chicago":"Aziz, Wajeeha, Wen Wang, Sebnem Kesaf, Alsayed Mohamed, Yugo Fukazawa, and Ryuichi Shigemoto. “Distinct Kinetics of Synaptic Structural Plasticity, Memory Formation, and Memory Decay in Massed and Spaced Learning.” <i>PNAS</i>. National Academy of Sciences, 2014. <a href=\"https://doi.org/10.1073/pnas.1303317110\">https://doi.org/10.1073/pnas.1303317110</a>.","short":"W. Aziz, W. Wang, S. Kesaf, A. Mohamed, Y. Fukazawa, R. Shigemoto, PNAS 111 (2014) E194–E202.","apa":"Aziz, W., Wang, W., Kesaf, S., Mohamed, A., Fukazawa, Y., &#38; Shigemoto, R. (2014). Distinct kinetics of synaptic structural plasticity, memory formation, and memory decay in massed and spaced learning. <i>PNAS</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.1303317110\">https://doi.org/10.1073/pnas.1303317110</a>","ama":"Aziz W, Wang W, Kesaf S, Mohamed A, Fukazawa Y, Shigemoto R. Distinct kinetics of synaptic structural plasticity, memory formation, and memory decay in massed and spaced learning. <i>PNAS</i>. 2014;111(1):E194-E202. doi:<a href=\"https://doi.org/10.1073/pnas.1303317110\">10.1073/pnas.1303317110</a>","mla":"Aziz, Wajeeha, et al. “Distinct Kinetics of Synaptic Structural Plasticity, Memory Formation, and Memory Decay in Massed and Spaced Learning.” <i>PNAS</i>, vol. 111, no. 1, National Academy of Sciences, 2014, pp. E194–202, doi:<a href=\"https://doi.org/10.1073/pnas.1303317110\">10.1073/pnas.1303317110</a>.","ieee":"W. Aziz, W. Wang, S. Kesaf, A. Mohamed, Y. Fukazawa, and R. Shigemoto, “Distinct kinetics of synaptic structural plasticity, memory formation, and memory decay in massed and spaced learning,” <i>PNAS</i>, vol. 111, no. 1. National Academy of Sciences, pp. E194–E202, 2014.","ista":"Aziz W, Wang W, Kesaf S, Mohamed A, Fukazawa Y, Shigemoto R. 2014. Distinct kinetics of synaptic structural plasticity, memory formation, and memory decay in massed and spaced learning. PNAS. 111(1), E194–E202."},"scopus_import":"1","author":[{"last_name":"Aziz","first_name":"Wajeeha","full_name":"Aziz, Wajeeha"},{"full_name":"Wang, Wen","last_name":"Wang","first_name":"Wen"},{"full_name":"Kesaf, Sebnem","first_name":"Sebnem","id":"401AB46C-F248-11E8-B48F-1D18A9856A87","last_name":"Kesaf"},{"last_name":"Mohamed","first_name":"Alsayed","full_name":"Mohamed, Alsayed"},{"full_name":"Fukazawa, Yugo","first_name":"Yugo","last_name":"Fukazawa"},{"last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","first_name":"Ryuichi","full_name":"Shigemoto, Ryuichi"}],"_id":"1919","publisher":"National Academy of Sciences","intvolume":"       111","type":"journal_article","isi":1,"page":"E194 - E202","publist_id":"5175","year":"2014","publication":"PNAS","external_id":{"isi":["000329350700025"]},"title":"Distinct kinetics of synaptic structural plasticity, memory formation, and memory decay in massed and spaced learning","volume":111,"acknowledgement":"his work was supported by Solution Oriented Research for Science and Technology (R.S.), Core Research for Evolutional Science and Technology, Japan Science and Technology Agency (Y.F.), and Grants-in-Aid for Scientific Research on Priority Areas-Molecular Brain Sciences 16300114 (to R.S.) and 18022043 (to Y.F.).","date_created":"2018-12-11T11:54:43Z","article_processing_charge":"No","department":[{"_id":"RySh"}]},{"publisher":"National Academy of Sciences","intvolume":"       111","isi":1,"type":"journal_article","citation":{"mla":"Wang, Wen, et al. “Distinct Cerebellar Engrams in Short-Term and Long-Term Motor Learning.” <i>PNAS</i>, vol. 111, no. 1, National Academy of Sciences, 2014, pp. E188–93, doi:<a href=\"https://doi.org/10.1073/pnas.1315541111\">10.1073/pnas.1315541111</a>.","ieee":"W. Wang <i>et al.</i>, “Distinct cerebellar engrams in short-term and long-term motor learning,” <i>PNAS</i>, vol. 111, no. 1. National Academy of Sciences, pp. E188–E193, 2014.","ista":"Wang W, Nakadate K, Masugi Tokita M, Shutoh F, Aziz W, Tarusawa E, Lörincz A, Molnár E, Kesaf S, Li Y, Fukazawa Y, Nagao S, Shigemoto R. 2014. Distinct cerebellar engrams in short-term and long-term motor learning. PNAS. 111(1), E188–E193.","ama":"Wang W, Nakadate K, Masugi Tokita M, et al. Distinct cerebellar engrams in short-term and long-term motor learning. <i>PNAS</i>. 2014;111(1):E188-E193. doi:<a href=\"https://doi.org/10.1073/pnas.1315541111\">10.1073/pnas.1315541111</a>","short":"W. Wang, K. Nakadate, M. Masugi Tokita, F. Shutoh, W. Aziz, E. Tarusawa, A. Lörincz, E. Molnár, S. Kesaf, Y. Li, Y. Fukazawa, S. Nagao, R. Shigemoto, PNAS 111 (2014) E188–E193.","apa":"Wang, W., Nakadate, K., Masugi Tokita, M., Shutoh, F., Aziz, W., Tarusawa, E., … Shigemoto, R. (2014). Distinct cerebellar engrams in short-term and long-term motor learning. <i>PNAS</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.1315541111\">https://doi.org/10.1073/pnas.1315541111</a>","chicago":"Wang, Wen, Kazuhiko Nakadate, Miwako Masugi Tokita, Fumihiro Shutoh, Wajeeha Aziz, Etsuko Tarusawa, Andrea Lörincz, et al. “Distinct Cerebellar Engrams in Short-Term and Long-Term Motor Learning.” <i>PNAS</i>. National Academy of Sciences, 2014. <a href=\"https://doi.org/10.1073/pnas.1315541111\">https://doi.org/10.1073/pnas.1315541111</a>."},"scopus_import":"1","_id":"1920","author":[{"full_name":"Wang, Wen","last_name":"Wang","first_name":"Wen"},{"full_name":"Nakadate, Kazuhiko","first_name":"Kazuhiko","last_name":"Nakadate"},{"last_name":"Masugi Tokita","first_name":"Miwako","full_name":"Masugi Tokita, Miwako"},{"last_name":"Shutoh","first_name":"Fumihiro","full_name":"Shutoh, Fumihiro"},{"full_name":"Aziz, Wajeeha","first_name":"Wajeeha","last_name":"Aziz"},{"first_name":"Etsuko","last_name":"Tarusawa","full_name":"Tarusawa, Etsuko"},{"last_name":"Lörincz","first_name":"Andrea","full_name":"Lörincz, Andrea"},{"first_name":"Elek","last_name":"Molnár","full_name":"Molnár, Elek"},{"full_name":"Kesaf, Sebnem","first_name":"Sebnem","last_name":"Kesaf","id":"401AB46C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Li, Yunqing","first_name":"Yunqing","last_name":"Li"},{"first_name":"Yugo","last_name":"Fukazawa","full_name":"Fukazawa, Yugo"},{"full_name":"Nagao, Soichi","last_name":"Nagao","first_name":"Soichi"},{"full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto","first_name":"Ryuichi"}],"article_processing_charge":"No","date_created":"2018-12-11T11:54:43Z","acknowledgement":"This work was supported by Solution-Oriented Research for Science and Technology from the Japan Science and Technology Agency; Ministry of Education, Culture, Sports, Science and Technology of Japan Grant 16300114 (to R.S.).","department":[{"_id":"RySh"}],"publist_id":"5174","page":"E188 - E193","publication":"PNAS","year":"2014","volume":111,"title":"Distinct cerebellar engrams in short-term and long-term motor learning","external_id":{"isi":["000329350700024"]},"day":"07","corr_author":"1","oa_version":"Submitted Version","date_updated":"2025-09-29T12:18:06Z","issue":"1","oa":1,"language":[{"iso":"eng"}],"main_file_link":[{"url":"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890858/","open_access":"1"}],"month":"01","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","doi":"10.1073/pnas.1315541111","abstract":[{"lang":"eng","text":"Cerebellar motor learning is suggested to be caused by long-term plasticity of excitatory parallel fiber-Purkinje cell (PF-PC) synapses associated with changes in the number of synaptic AMPA-type glutamate receptors (AMPARs). However, whether the AMPARs decrease or increase in individual PF-PC synapses occurs in physiological motor learning and accounts for memory that lasts over days remains elusive. We combined quantitative SDS-digested freeze-fracture replica labeling for AMPAR and physical dissector electron microscopy with a simple model of cerebellar motor learning, adaptation of horizontal optokinetic response (HOKR) in mouse. After 1-h training of HOKR, short-term adaptation (STA) was accompanied with transient decrease in AMPARs by 28% in target PF-PC synapses. STA was well correlated with AMPAR decrease in individual animals and both STA and AMPAR decrease recovered to basal levels within 24 h. Surprisingly, long-termadaptation (LTA) after five consecutive daily trainings of 1-h HOKR did not alter the number of AMPARs in PF-PC synapses but caused gradual and persistent synapse elimination by 45%, with corresponding PC spine loss by the fifth training day. Furthermore, recovery of LTA after 2 wk was well correlated with increase of PF-PC synapses to the control level. Our findings indicate that the AMPARs decrease in PF-PC synapses and the elimination of these synapses are in vivo engrams in short- and long-term motor learning, respectively, showing a unique type of synaptic plasticity that may contribute to memory consolidation."}],"publication_status":"published","status":"public","date_published":"2014-01-07T00:00:00Z"},{"citation":{"short":"J. Hatakeyama, Y. Wakamatsu, A. Nagafuchi, R. Kageyama, R. Shigemoto, K. Shimamura, Development 141 (2014) 1671–1682.","apa":"Hatakeyama, J., Wakamatsu, Y., Nagafuchi, A., Kageyama, R., Shigemoto, R., &#38; Shimamura, K. (2014). Cadherin-based adhesions in the apical endfoot are required for active Notch signaling to control neurogenesis in vertebrates. <i>Development</i>. Company of Biologists. <a href=\"https://doi.org/10.1242/dev.102988\">https://doi.org/10.1242/dev.102988</a>","chicago":"Hatakeyama, Jun, Yoshio Wakamatsu, Akira Nagafuchi, Ryoichiro Kageyama, Ryuichi Shigemoto, and Kenji Shimamura. “Cadherin-Based Adhesions in the Apical Endfoot Are Required for Active Notch Signaling to Control Neurogenesis in Vertebrates.” <i>Development</i>. Company of Biologists, 2014. <a href=\"https://doi.org/10.1242/dev.102988\">https://doi.org/10.1242/dev.102988</a>.","ista":"Hatakeyama J, Wakamatsu Y, Nagafuchi A, Kageyama R, Shigemoto R, Shimamura K. 2014. Cadherin-based adhesions in the apical endfoot are required for active Notch signaling to control neurogenesis in vertebrates. Development. 141(8), 1671–1682.","ieee":"J. Hatakeyama, Y. Wakamatsu, A. Nagafuchi, R. Kageyama, R. Shigemoto, and K. Shimamura, “Cadherin-based adhesions in the apical endfoot are required for active Notch signaling to control neurogenesis in vertebrates,” <i>Development</i>, vol. 141, no. 8. Company of Biologists, pp. 1671–1682, 2014.","mla":"Hatakeyama, Jun, et al. “Cadherin-Based Adhesions in the Apical Endfoot Are Required for Active Notch Signaling to Control Neurogenesis in Vertebrates.” <i>Development</i>, vol. 141, no. 8, Company of Biologists, 2014, pp. 1671–82, doi:<a href=\"https://doi.org/10.1242/dev.102988\">10.1242/dev.102988</a>.","ama":"Hatakeyama J, Wakamatsu Y, Nagafuchi A, Kageyama R, Shigemoto R, Shimamura K. Cadherin-based adhesions in the apical endfoot are required for active Notch signaling to control neurogenesis in vertebrates. <i>Development</i>. 2014;141(8):1671-1682. doi:<a href=\"https://doi.org/10.1242/dev.102988\">10.1242/dev.102988</a>"},"scopus_import":"1","quality_controlled":"1","_id":"1933","author":[{"full_name":"Hatakeyama, Jun","last_name":"Hatakeyama","first_name":"Jun"},{"full_name":"Wakamatsu, Yoshio","last_name":"Wakamatsu","first_name":"Yoshio"},{"first_name":"Akira","last_name":"Nagafuchi","full_name":"Nagafuchi, Akira"},{"first_name":"Ryoichiro","last_name":"Kageyama","full_name":"Kageyama, Ryoichiro"},{"full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","first_name":"Ryuichi"},{"full_name":"Shimamura, Kenji","last_name":"Shimamura","first_name":"Kenji"}],"publisher":"Company of Biologists","intvolume":"       141","isi":1,"type":"journal_article","publist_id":"5161","page":"1671 - 1682","publication":"Development","year":"2014","volume":141,"title":"Cadherin-based adhesions in the apical endfoot are required for active Notch signaling to control neurogenesis in vertebrates","external_id":{"isi":["000334347900007"]},"article_processing_charge":"No","date_created":"2018-12-11T11:54:47Z","department":[{"_id":"RySh"}],"date_updated":"2025-09-29T12:10:15Z","oa_version":"None","issue":"8","language":[{"iso":"eng"}],"day":"01","abstract":[{"lang":"eng","text":"The development of the vertebrate brain requires an exquisite balance between proliferation and differentiation of neural progenitors. Notch signaling plays a pivotal role in regulating this balance, yet the interaction between signaling and receiving cells remains poorly understood. We have found that numerous nascent neurons and/or intermediate neurogenic progenitors expressing the ligand of Notch retain apical endfeet transiently at the ventricular lumen that form adherens junctions (AJs) with the endfeet of progenitors. Forced detachment of the apical endfeet of those differentiating cells by disrupting AJs resulted in precocious neurogenesis that was preceded by the downregulation of Notch signaling. Both Notch1 and its ligand Dll1 are distributed around AJs in the apical endfeet, and these proteins physically interact with ZO-1, a constituent of the AJ. Furthermore, live imaging of a fluorescently tagged Notch1 demonstrated its trafficking from the apical endfoot to the nucleus upon cleavage. Our results identified the apical endfoot as the central site of active Notch signaling to securely prohibit inappropriate differentiation of neural progenitors."}],"publication_status":"published","status":"public","date_published":"2014-04-01T00:00:00Z","month":"04","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","doi":"10.1242/dev.102988"},{"article_processing_charge":"No","date_created":"2018-12-11T11:56:31Z","publication_identifier":{"issn":["0896-6273"]},"department":[{"_id":"RySh"}],"publist_id":"4715","page":"314 - 320","volume":81,"external_id":{"isi":["000330420700010"]},"title":"Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage","publication":"Neuron","year":"2014","intvolume":"        81","publisher":"Elsevier","isi":1,"type":"journal_article","scopus_import":"1","quality_controlled":"1","citation":{"ieee":"K. Beppu <i>et al.</i>, “Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage,” <i>Neuron</i>, vol. 81, no. 2. Elsevier, pp. 314–320, 2014.","mla":"Beppu, Kaoru, et al. “Optogenetic Countering of Glial Acidosis Suppresses Glial Glutamate Release and Ischemic Brain Damage.” <i>Neuron</i>, vol. 81, no. 2, Elsevier, 2014, pp. 314–20, doi:<a href=\"https://doi.org/10.1016/j.neuron.2013.11.011\">10.1016/j.neuron.2013.11.011</a>.","ista":"Beppu K, Sasaki T, Tanaka K, Yamanaka A, Fukazawa Y, Shigemoto R, Matsui K. 2014. Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage. Neuron. 81(2), 314–320.","ama":"Beppu K, Sasaki T, Tanaka K, et al. Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage. <i>Neuron</i>. 2014;81(2):314-320. doi:<a href=\"https://doi.org/10.1016/j.neuron.2013.11.011\">10.1016/j.neuron.2013.11.011</a>","short":"K. Beppu, T. Sasaki, K. Tanaka, A. Yamanaka, Y. Fukazawa, R. Shigemoto, K. Matsui, Neuron 81 (2014) 314–320.","apa":"Beppu, K., Sasaki, T., Tanaka, K., Yamanaka, A., Fukazawa, Y., Shigemoto, R., &#38; Matsui, K. (2014). Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2013.11.011\">https://doi.org/10.1016/j.neuron.2013.11.011</a>","chicago":"Beppu, Kaoru, Takuya Sasaki, Kenji Tanaka, Akihiro Yamanaka, Yugo Fukazawa, Ryuichi Shigemoto, and Ko Matsui. “Optogenetic Countering of Glial Acidosis Suppresses Glial Glutamate Release and Ischemic Brain Damage.” <i>Neuron</i>. Elsevier, 2014. <a href=\"https://doi.org/10.1016/j.neuron.2013.11.011\">https://doi.org/10.1016/j.neuron.2013.11.011</a>."},"_id":"2241","author":[{"full_name":"Beppu, Kaoru","last_name":"Beppu","first_name":"Kaoru"},{"full_name":"Sasaki, Takuya","first_name":"Takuya","last_name":"Sasaki"},{"full_name":"Tanaka, Kenji","first_name":"Kenji","last_name":"Tanaka"},{"full_name":"Yamanaka, Akihiro","first_name":"Akihiro","last_name":"Yamanaka"},{"full_name":"Fukazawa, Yugo","last_name":"Fukazawa","first_name":"Yugo"},{"full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444"},{"first_name":"Ko","last_name":"Matsui","full_name":"Matsui, Ko"}],"month":"01","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","doi":"10.1016/j.neuron.2013.11.011","abstract":[{"lang":"eng","text":"The brain demands high-energy supply and obstruction of blood flow causes rapid deterioration of the healthiness of brain cells. Two major events occur upon ischemia: acidosis and liberation of excess glutamate, which leads to excitotoxicity. However, cellular source of glutamate and its release mechanism upon ischemia remained unknown. Here we show a causal relationship between glial acidosis and neuronal excitotoxicity. As the major cation that flows through channelrhodopsin-2 (ChR2) is proton, this could be regarded as an optogenetic tool for instant intracellular acidification. Optical activation of ChR2 expressed in glial cells led to glial acidification and to release of glutamate. On the other hand, glial alkalization via optogenetic activation of a proton pump, archaerhodopsin (ArchT), led to cessation of glutamate release and to the relief of ischemic brain damage in vivo. Our results suggest that controlling glial pH may be an effective therapeutic strategy for intervention of ischemic brain damage."}],"publication_status":"published","date_published":"2014-01-22T00:00:00Z","status":"public","day":"22","oa_version":"None","date_updated":"2026-04-16T10:07:56Z","issue":"2","language":[{"iso":"eng"}]}]