[{"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.).","scopus_import":1,"date_updated":"2021-01-12T06:54:04Z","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","language":[{"iso":"eng"}],"doi":"10.1073/pnas.1303317110","citation":{"short":"W. Aziz, W. Wang, S. Kesaf, A. Mohamed, Y. Fukazawa, R. Shigemoto, PNAS 111 (2014) E194–E202.","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>","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>","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>.","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.","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.","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>."},"title":"Distinct kinetics of synaptic structural plasticity, memory formation, and memory decay in massed and spaced learning","day":"07","publist_id":"5175","type":"journal_article","author":[{"first_name":"Wajeeha","full_name":"Aziz, Wajeeha","last_name":"Aziz"},{"first_name":"Wen","full_name":"Wang, Wen","last_name":"Wang"},{"id":"401AB46C-F248-11E8-B48F-1D18A9856A87","last_name":"Kesaf","full_name":"Kesaf, Sebnem","first_name":"Sebnem"},{"last_name":"Mohamed","first_name":"Alsayed","full_name":"Mohamed, Alsayed"},{"first_name":"Yugo","full_name":"Fukazawa, Yugo","last_name":"Fukazawa"},{"orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto","first_name":"Ryuichi","full_name":"Shigemoto, Ryuichi"}],"oa_version":"Submitted Version","year":"2014","publication_status":"published","publisher":"National Academy of Sciences","oa":1,"main_file_link":[{"open_access":"1","url":"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890840/"}],"publication":"PNAS","department":[{"_id":"RySh"}],"status":"public","intvolume":"       111","volume":111,"page":"E194 - E202","issue":"1","month":"01","_id":"1919","date_published":"2014-01-07T00:00:00Z","date_created":"2018-12-11T11:54:43Z","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."}]},{"_id":"1920","date_created":"2018-12-11T11:54:43Z","abstract":[{"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.","lang":"eng"}],"date_published":"2014-01-07T00:00:00Z","month":"01","issue":"1","page":"E188 - E193","volume":111,"status":"public","intvolume":"       111","department":[{"_id":"RySh"}],"publication":"PNAS","main_file_link":[{"url":"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890858/","open_access":"1"}],"oa":1,"publisher":"National Academy of Sciences","publication_status":"published","year":"2014","oa_version":"Submitted Version","type":"journal_article","author":[{"first_name":"Wen","full_name":"Wang, Wen","last_name":"Wang"},{"last_name":"Nakadate","full_name":"Nakadate, Kazuhiko","first_name":"Kazuhiko"},{"full_name":"Masugi Tokita, Miwako","first_name":"Miwako","last_name":"Masugi Tokita"},{"first_name":"Fumihiro","full_name":"Shutoh, Fumihiro","last_name":"Shutoh"},{"last_name":"Aziz","first_name":"Wajeeha","full_name":"Aziz, Wajeeha"},{"first_name":"Etsuko","full_name":"Tarusawa, Etsuko","last_name":"Tarusawa"},{"last_name":"Lörincz","full_name":"Lörincz, Andrea","first_name":"Andrea"},{"full_name":"Molnár, Elek","first_name":"Elek","last_name":"Molnár"},{"id":"401AB46C-F248-11E8-B48F-1D18A9856A87","full_name":"Kesaf, Sebnem","first_name":"Sebnem","last_name":"Kesaf"},{"first_name":"Yunqing","full_name":"Li, Yunqing","last_name":"Li"},{"last_name":"Fukazawa","full_name":"Fukazawa, Yugo","first_name":"Yugo"},{"last_name":"Nagao","first_name":"Soichi","full_name":"Nagao, Soichi"},{"last_name":"Shigemoto","first_name":"Ryuichi","full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87"}],"day":"07","publist_id":"5174","title":"Distinct cerebellar engrams in short-term and long-term motor learning","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>.","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>.","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>","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>","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."},"doi":"10.1073/pnas.1315541111","date_updated":"2021-01-12T06:54:05Z","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","language":[{"iso":"eng"}],"scopus_import":1,"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.)."},{"month":"04","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."}],"_id":"1933","date_created":"2018-12-11T11:54:47Z","date_published":"2014-04-01T00:00:00Z","page":"1671 - 1682","issue":"8","quality_controlled":"1","department":[{"_id":"RySh"}],"publication":"Development","volume":141,"intvolume":"       141","status":"public","publication_status":"published","publisher":"Company of Biologists","day":"01","publist_id":"5161","oa_version":"None","year":"2014","author":[{"last_name":"Hatakeyama","first_name":"Jun","full_name":"Hatakeyama, Jun"},{"last_name":"Wakamatsu","full_name":"Wakamatsu, Yoshio","first_name":"Yoshio"},{"first_name":"Akira","full_name":"Nagafuchi, Akira","last_name":"Nagafuchi"},{"first_name":"Ryoichiro","full_name":"Kageyama, Ryoichiro","last_name":"Kageyama"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","first_name":"Ryuichi","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto"},{"last_name":"Shimamura","first_name":"Kenji","full_name":"Shimamura, Kenji"}],"type":"journal_article","citation":{"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>.","short":"J. Hatakeyama, Y. Wakamatsu, A. Nagafuchi, R. Kageyama, R. Shigemoto, K. Shimamura, Development 141 (2014) 1671–1682.","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>","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>"},"title":"Cadherin-based adhesions in the apical endfoot are required for active Notch signaling to control neurogenesis in vertebrates","date_updated":"2021-01-12T06:54:10Z","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","language":[{"iso":"eng"}],"scopus_import":1,"doi":"10.1242/dev.102988"},{"page":"15779 - 15792","month":"11","date_created":"2018-12-11T11:55:14Z","publisher":"Society for Neuroscience","department":[{"_id":"RySh"}],"quality_controlled":"1","publication":"Journal of Neuroscience","status":"public","intvolume":"        34","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.","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>.","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>.","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>","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>"},"title":"Netrin-G/NGL complexes encode functional synaptic diversification","day":"19","author":[{"last_name":"Matsukawa","full_name":"Matsukawa, Hiroshi","first_name":"Hiroshi"},{"full_name":"Akiyoshi Nishimura, Sachiko","first_name":"Sachiko","last_name":"Akiyoshi Nishimura"},{"last_name":"Zhang","full_name":"Zhang, Qi","first_name":"Qi"},{"last_name":"Luján","first_name":"Rafael","full_name":"Luján, Rafael"},{"last_name":"Yamaguchi","first_name":"Kazuhiko","full_name":"Yamaguchi, Kazuhiko"},{"last_name":"Goto","first_name":"Hiromichi","full_name":"Goto, Hiromichi"},{"last_name":"Yaguchi","full_name":"Yaguchi, Kunio","first_name":"Kunio"},{"first_name":"Tsutomu","full_name":"Hashikawa, Tsutomu","last_name":"Hashikawa"},{"last_name":"Sano","full_name":"Sano, Chie","first_name":"Chie"},{"orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto"},{"last_name":"Nakashiba","full_name":"Nakashiba, Toshiaki","first_name":"Toshiaki"},{"first_name":"Shigeyoshi","full_name":"Itohara, Shigeyoshi","last_name":"Itohara"}],"type":"journal_article","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.","pmid":1,"language":[{"iso":"eng"}],"ddc":["570"],"doi":"10.1523/JNEUROSCI.1141-14.2014","issue":"47","article_processing_charge":"No","file":[{"file_size":3963728,"creator":"dernst","file_name":"2014_JournNeuroscience_Matsukawa.pdf","access_level":"open_access","date_updated":"2022-05-24T08:41:41Z","checksum":"6913e9bc26e9fc1c0441a739a4199229","file_id":"11410","relation":"main_file","content_type":"application/pdf","success":1,"date_created":"2022-05-24T08:41:41Z"}],"date_published":"2014-11-19T00:00:00Z","_id":"2018","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"}],"publication_status":"published","oa":1,"file_date_updated":"2022-05-24T08:41:41Z","volume":34,"publist_id":"5054","article_type":"original","has_accepted_license":"1","oa_version":"Published Version","year":"2014","date_updated":"2022-05-24T08:54:54Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","external_id":{"pmid":["25411505"]},"scopus_import":"1","publication_identifier":{"eissn":["1529-2401"],"issn":["0270-6474"]}},{"main_file_link":[{"open_access":"1","url":"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198489/"}],"oa":1,"publication_status":"published","volume":522,"issue":"18","_id":"2064","abstract":[{"lang":"eng","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."}],"date_published":"2014-07-29T00:00:00Z","date_updated":"2021-01-12T06:55:05Z","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","scopus_import":1,"year":"2014","oa_version":"Submitted Version","publist_id":"4974","publisher":"Wiley-Blackwell","status":"public","intvolume":"       522","quality_controlled":"1","department":[{"_id":"RySh"}],"publication":"Journal of Comparative Neurology","page":"4023 - 4042","date_created":"2018-12-11T11:55:30Z","month":"07","acknowledgement":"National Institutes of Health (NIH) Grant Number: 1R01DC013048‐0; Biotechnology and Biological Sciences Research Council, UK Grant Number: BB/J015938/1\r\n","doi":"10.1002/cne.23654","language":[{"iso":"eng"}],"title":"Target- and input-dependent organization of AMPA and NMDA receptors in synaptic connections of the cochlear nucleus","citation":{"short":"M. Rubio, Y. Fukazawa, N. Kamasawa, C. Clarkson, E. Molnár, R. Shigemoto, Journal of Comparative Neurology 522 (2014) 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>","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>.","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.","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>."},"author":[{"last_name":"Rubio","full_name":"Rubio, Maía","first_name":"Maía"},{"first_name":"Yugo","full_name":"Fukazawa, Yugo","last_name":"Fukazawa"},{"last_name":"Kamasawa","full_name":"Kamasawa, Naomi","first_name":"Naomi"},{"last_name":"Clarkson","full_name":"Clarkson, Cheryl","first_name":"Cheryl"},{"full_name":"Molnár, Elek","first_name":"Elek","last_name":"Molnár"},{"last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444"}],"type":"journal_article","day":"29"},{"doi":"10.1016/j.neuron.2013.11.011","publication_identifier":{"issn":["08966273"]},"language":[{"iso":"eng"}],"user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","date_updated":"2021-01-12T06:56:14Z","scopus_import":1,"year":"2014","oa_version":"None","author":[{"full_name":"Beppu, Kaoru","first_name":"Kaoru","last_name":"Beppu"},{"last_name":"Sasaki","full_name":"Sasaki, Takuya","first_name":"Takuya"},{"last_name":"Tanaka","full_name":"Tanaka, Kenji","first_name":"Kenji"},{"first_name":"Akihiro","full_name":"Yamanaka, Akihiro","last_name":"Yamanaka"},{"full_name":"Fukazawa, Yugo","first_name":"Yugo","last_name":"Fukazawa"},{"full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444"},{"last_name":"Matsui","first_name":"Ko","full_name":"Matsui, Ko"}],"type":"journal_article","day":"22","publist_id":"4715","title":"Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage","citation":{"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>.","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>.","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.","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>","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>","short":"K. Beppu, T. Sasaki, K. Tanaka, A. Yamanaka, Y. Fukazawa, R. Shigemoto, K. Matsui, Neuron 81 (2014) 314–320."},"volume":81,"intvolume":"        81","status":"public","department":[{"_id":"RySh"}],"quality_controlled":"1","publication":"Neuron","publisher":"Elsevier","publication_status":"published","_id":"2241","abstract":[{"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.","lang":"eng"}],"date_published":"2014-01-22T00:00:00Z","date_created":"2018-12-11T11:56:31Z","month":"01","issue":"2","page":"314 - 320"}]