--- _id: '1278' abstract: - lang: eng 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 (< 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. 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]. article_number: e0164037 article_processing_charge: No article_type: original author: - first_name: Hitomi full_name: Matsuno, Hitomi last_name: Matsuno - first_name: Moeko full_name: Kudoh, Moeko last_name: Kudoh - first_name: Akiya full_name: Watakabe, Akiya last_name: Watakabe - first_name: Tetsuo full_name: Yamamori, Tetsuo last_name: Yamamori - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Soichi full_name: Nagao, Soichi last_name: Nagao 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. PLoS One. 2016;11(10). doi:10.1371/journal.pone.0164037' apa: '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. Public Library of Science. https://doi.org/10.1371/journal.pone.0164037' 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.” PLoS One. Public Library of Science, 2016. https://doi.org/10.1371/journal.pone.0164037.' 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,” PLoS One, vol. 11, no. 10. Public Library of Science, 2016.' 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.” PLoS One, vol. 11, no. 10, e0164037, Public Library of Science, 2016, doi:10.1371/journal.pone.0164037.' short: H. Matsuno, M. Kudoh, A. Watakabe, T. Yamamori, R. Shigemoto, S. Nagao, PLoS One 11 (2016). date_created: 2018-12-11T11:51:06Z date_published: 2016-10-06T00:00:00Z date_updated: 2021-01-12T06:49:34Z day: '06' ddc: - '570' - '571' department: - _id: RySh doi: 10.1371/journal.pone.0164037 file: - access_level: open_access checksum: 7c0ba0ca6d79844059158059d2a38d25 content_type: application/pdf creator: system date_created: 2018-12-12T10:17:16Z date_updated: 2020-07-14T12:44:42Z file_id: '5269' file_name: IST-2016-689-v1+1_journal.pone.0164037.PDF file_size: 3657084 relation: main_file file_date_updated: 2020-07-14T12:44:42Z has_accepted_license: '1' intvolume: ' 11' issue: '10' language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '10' oa: 1 oa_version: Published Version publication: PLoS One publication_status: published publisher: Public Library of Science publist_id: '6038' pubrep_id: '689' quality_controlled: '1' scopus_import: 1 status: public 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' tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 11 year: '2016' ... --- _id: '1094' abstract: - lang: eng 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. acknowledged_ssus: - _id: EM-Fac 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). ' alternative_title: - Methods in Molecular Biology article_processing_charge: No author: - first_name: Harumi full_name: Harada, Harumi id: 2E55CDF2-F248-11E8-B48F-1D18A9856A87 last_name: Harada orcid: 0000-0001-7429-7896 - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: ama: 'Harada H, Shigemoto R. Immunogold protein localization on grid-glued freeze-fracture replicas. In: High-Resolution Imaging of Cellular Proteins. Vol 1474. Springer; 2016:203-216. doi:10.1007/978-1-4939-6352-2_12' apa: Harada, H., & Shigemoto, R. (2016). Immunogold protein localization on grid-glued freeze-fracture replicas. In High-Resolution Imaging of Cellular Proteins (Vol. 1474, pp. 203–216). Springer. https://doi.org/10.1007/978-1-4939-6352-2_12 chicago: Harada, Harumi, and Ryuichi Shigemoto. “Immunogold Protein Localization on Grid-Glued Freeze-Fracture Replicas.” In High-Resolution Imaging of Cellular Proteins, 1474:203–16. Springer, 2016. https://doi.org/10.1007/978-1-4939-6352-2_12. ieee: H. Harada and R. Shigemoto, “Immunogold protein localization on grid-glued freeze-fracture replicas,” in High-Resolution Imaging of Cellular Proteins, vol. 1474, Springer, 2016, pp. 203–216. 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.' mla: Harada, Harumi, and Ryuichi Shigemoto. “Immunogold Protein Localization on Grid-Glued Freeze-Fracture Replicas.” High-Resolution Imaging of Cellular Proteins, vol. 1474, Springer, 2016, pp. 203–16, doi:10.1007/978-1-4939-6352-2_12. short: H. Harada, R. Shigemoto, in:, High-Resolution Imaging of Cellular Proteins, Springer, 2016, pp. 203–216. date_created: 2018-12-11T11:50:06Z date_published: 2016-08-12T00:00:00Z date_updated: 2023-09-05T14:09:01Z day: '12' department: - _id: RySh doi: 10.1007/978-1-4939-6352-2_12 ec_funded: 1 intvolume: ' 1474' language: - iso: eng month: '08' oa_version: None page: 203 - 216 project: - _id: 25CD3DD2-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '604102' name: Localization of ion channels and receptors by two and three-dimensional immunoelectron microscopic approaches publication: High-Resolution Imaging of Cellular Proteins publication_identifier: eissn: - 1611-3349 issn: - 0302-9743 publication_status: published publisher: Springer publist_id: '6281' quality_controlled: '1' status: public title: Immunogold protein localization on grid-glued freeze-fracture replicas type: book_chapter user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 1474 year: '2016' ... --- _id: '1546' 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 (<30nm) and predict that VGCC number per cluster determines vesicular release probability without altering release time course. This "perimeter release model" provides a unifying framework accounting for developmental changes in both synaptic efficacy and time course. 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. author: - first_name: Yukihiro full_name: Nakamura, Yukihiro last_name: Nakamura - first_name: Harumi full_name: Harada, Harumi id: 2E55CDF2-F248-11E8-B48F-1D18A9856A87 last_name: Harada orcid: 0000-0001-7429-7896 - first_name: Naomi full_name: Kamasawa, Naomi last_name: Kamasawa - first_name: Ko full_name: Matsui, Ko last_name: Matsui - first_name: Jason full_name: Rothman, Jason last_name: Rothman - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: R Angus full_name: Silver, R Angus last_name: Silver - first_name: David full_name: Digregorio, David last_name: Digregorio - first_name: Tomoyuki full_name: Takahashi, Tomoyuki last_name: Takahashi citation: ama: Nakamura Y, Harada H, Kamasawa N, et al. Nanoscale distribution of presynaptic Ca2+ channels and its impact on vesicular release during development. Neuron. 2015;85(1):145-158. doi:10.1016/j.neuron.2014.11.019 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. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2014.11.019 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.” Neuron. Elsevier, 2015. https://doi.org/10.1016/j.neuron.2014.11.019. ieee: Y. Nakamura et al., “Nanoscale distribution of presynaptic Ca2+ channels and its impact on vesicular release during development,” Neuron, vol. 85, no. 1. Elsevier, pp. 145–158, 2015. 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.” Neuron, vol. 85, no. 1, Elsevier, 2015, pp. 145–58, doi:10.1016/j.neuron.2014.11.019. 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. date_created: 2018-12-11T11:52:39Z date_published: 2015-01-07T00:00:00Z date_updated: 2021-01-12T06:51:31Z day: '07' ddc: - '570' department: - _id: RySh doi: 10.1016/j.neuron.2014.11.019 file: - access_level: open_access checksum: 725f4d5be2dbb44b283ce722645ef37d content_type: application/pdf creator: system date_created: 2018-12-12T10:15:47Z date_updated: 2020-07-14T12:45:01Z file_id: '5170' file_name: IST-2016-482-v1+1_1-s2.0-S0896627314010472-main.pdf file_size: 3080111 relation: main_file file_date_updated: 2020-07-14T12:45:01Z has_accepted_license: '1' intvolume: ' 85' issue: '1' language: - iso: eng month: '01' oa: 1 oa_version: Published Version page: 145 - 158 publication: Neuron publication_status: published publisher: Elsevier publist_id: '5625' pubrep_id: '482' quality_controlled: '1' scopus_import: 1 status: public title: Nanoscale distribution of presynaptic Ca2+ channels and its impact on vesicular release during development tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 85 year: '2015' ... --- _id: '1557' 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. 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" author: - first_name: Fariba full_name: Javdani, Fariba last_name: Javdani - first_name: Krisztina full_name: Holló, Krisztina last_name: Holló - first_name: Krisztina full_name: Hegedűs, Krisztina last_name: Hegedűs - first_name: Gréta full_name: Kis, Gréta last_name: Kis - first_name: Zoltán full_name: Hegyi, Zoltán last_name: Hegyi - first_name: Klaudia full_name: Dócs, Klaudia last_name: Dócs - first_name: Yu full_name: Kasugai, Yu last_name: Kasugai - first_name: Yugo full_name: Fukazawa, Yugo last_name: Fukazawa - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Miklós full_name: Antal, Miklós last_name: Antal 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. Journal of Comparative Neurology. 2015;523(13):1967-1983. doi:10.1002/cne.23774 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. Journal of Comparative Neurology. Wiley-Blackwell. https://doi.org/10.1002/cne.23774 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.” Journal of Comparative Neurology. Wiley-Blackwell, 2015. https://doi.org/10.1002/cne.23774. ieee: F. Javdani et al., “Differential expression patterns of K+Cl- cotransporter 2 in neurons within the superficial spinal dorsal horn of rats,” Journal of Comparative Neurology, vol. 523, no. 13. Wiley-Blackwell, pp. 1967–1983, 2015. 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. mla: Javdani, Fariba, et al. “Differential Expression Patterns of K+Cl- Cotransporter 2 in Neurons within the Superficial Spinal Dorsal Horn of Rats.” Journal of Comparative Neurology, vol. 523, no. 13, Wiley-Blackwell, 2015, pp. 1967–83, doi:10.1002/cne.23774. 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. date_created: 2018-12-11T11:52:42Z date_published: 2015-09-01T00:00:00Z date_updated: 2021-01-12T06:51:35Z day: '01' department: - _id: RySh doi: 10.1002/cne.23774 intvolume: ' 523' issue: '13' language: - iso: eng month: '09' oa_version: None page: 1967 - 1983 publication: Journal of Comparative Neurology publication_status: published publisher: Wiley-Blackwell publist_id: '5614' quality_controlled: '1' scopus_import: 1 status: public title: Differential expression patterns of K+Cl- cotransporter 2 in neurons within the superficial spinal dorsal horn of rats type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 523 year: '2015' ... --- _id: '1895' 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. 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. article_number: e107099 author: - first_name: Mitsuhiro full_name: Edamura, Mitsuhiro last_name: Edamura - first_name: Gen full_name: Murakami, Gen last_name: Murakami - first_name: Hongrui full_name: Meng, Hongrui last_name: Meng - first_name: Makoto full_name: Itakura, Makoto last_name: Itakura - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Atsuo full_name: Fukuda, Atsuo last_name: Fukuda - first_name: Daiichiro full_name: Nakahara, Daiichiro last_name: Nakahara citation: 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. PLoS One. 2014;9(9). doi:10.1371/journal.pone.0107099 apa: 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. Public Library of Science. https://doi.org/10.1371/journal.pone.0107099 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.” PLoS One. Public Library of Science, 2014. https://doi.org/10.1371/journal.pone.0107099. ieee: M. Edamura et al., “Functional deficiency of MHC class i enhances LTP and abolishes LTD in the nucleus accumbens of mice,” PLoS One, vol. 9, no. 9. Public Library of Science, 2014. 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. mla: Edamura, Mitsuhiro, et al. “Functional Deficiency of MHC Class i Enhances LTP and Abolishes LTD in the Nucleus Accumbens of Mice.” PLoS One, vol. 9, no. 9, e107099, Public Library of Science, 2014, doi:10.1371/journal.pone.0107099. short: M. Edamura, G. Murakami, H. Meng, M. Itakura, R. Shigemoto, A. Fukuda, D. Nakahara, PLoS One 9 (2014). date_created: 2018-12-11T11:54:35Z date_published: 2014-09-30T00:00:00Z date_updated: 2021-01-12T06:53:54Z day: '30' ddc: - '570' department: - _id: RySh doi: 10.1371/journal.pone.0107099 file: - access_level: open_access checksum: 1f3be936be93114596d61ba44cacee69 content_type: application/pdf creator: system date_created: 2018-12-12T10:09:01Z date_updated: 2020-07-14T12:45:20Z file_id: '4724' file_name: IST-2016-439-v1+1_journal.pone.0107099.pdf file_size: 6262085 relation: main_file file_date_updated: 2020-07-14T12:45:20Z has_accepted_license: '1' intvolume: ' 9' issue: '9' language: - iso: eng month: '09' oa: 1 oa_version: Published Version publication: PLoS One publication_status: published publisher: Public Library of Science publist_id: '5200' pubrep_id: '439' scopus_import: 1 status: public title: Functional deficiency of MHC class i enhances LTP and abolishes LTD in the nucleus accumbens of mice tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87 volume: 9 year: '2014' ... --- _id: '1898' 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. author: - first_name: Andreas full_name: Ritzau Jost, Andreas last_name: Ritzau Jost - first_name: Igor full_name: Delvendahl, Igor last_name: Delvendahl - first_name: Annika full_name: Rings, Annika last_name: Rings - first_name: Niklas full_name: Byczkowicz, Niklas last_name: Byczkowicz - first_name: Harumi full_name: Harada, Harumi id: 2E55CDF2-F248-11E8-B48F-1D18A9856A87 last_name: Harada orcid: 0000-0001-7429-7896 - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Johannes full_name: Hirrlinger, Johannes last_name: Hirrlinger - first_name: Jens full_name: Eilers, Jens last_name: Eilers - first_name: Stefan full_name: Hallermann, Stefan last_name: Hallermann citation: ama: Ritzau Jost A, Delvendahl I, Rings A, et al. Ultrafast action potentials mediate kilohertz signaling at a central synapse. Neuron. 2014;84(1):152-163. doi:10.1016/j.neuron.2014.08.036 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. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2014.08.036 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.” Neuron. Elsevier, 2014. https://doi.org/10.1016/j.neuron.2014.08.036. ieee: A. Ritzau Jost et al., “Ultrafast action potentials mediate kilohertz signaling at a central synapse,” Neuron, 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.” Neuron, vol. 84, no. 1, Elsevier, 2014, pp. 152–63, doi:10.1016/j.neuron.2014.08.036. 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. date_created: 2018-12-11T11:54:36Z date_published: 2014-10-01T00:00:00Z date_updated: 2021-01-12T06:53:55Z day: '01' department: - _id: RySh doi: 10.1016/j.neuron.2014.08.036 intvolume: ' 84' issue: '1' language: - iso: eng month: '10' oa_version: None page: 152 - 163 publication: Neuron publication_status: published publisher: Elsevier publist_id: '5197' quality_controlled: '1' scopus_import: 1 status: public title: Ultrafast action potentials mediate kilohertz signaling at a central synapse type: journal_article user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87 volume: 84 year: '2014' ... --- _id: '1920' 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. 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.). author: - first_name: Wen full_name: Wang, Wen last_name: Wang - first_name: Kazuhiko full_name: Nakadate, Kazuhiko last_name: Nakadate - first_name: Miwako full_name: Masugi Tokita, Miwako last_name: Masugi Tokita - first_name: Fumihiro full_name: Shutoh, Fumihiro last_name: Shutoh - first_name: Wajeeha full_name: Aziz, Wajeeha last_name: Aziz - first_name: Etsuko full_name: Tarusawa, Etsuko last_name: Tarusawa - first_name: Andrea full_name: Lörincz, Andrea last_name: Lörincz - first_name: Elek full_name: Molnár, Elek last_name: Molnár - first_name: Sebnem full_name: Kesaf, Sebnem id: 401AB46C-F248-11E8-B48F-1D18A9856A87 last_name: Kesaf - first_name: Yunqing full_name: Li, Yunqing last_name: Li - first_name: Yugo full_name: Fukazawa, Yugo last_name: Fukazawa - first_name: Soichi full_name: Nagao, Soichi last_name: Nagao - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: ama: Wang W, Nakadate K, Masugi Tokita M, et al. Distinct cerebellar engrams in short-term and long-term motor learning. PNAS. 2014;111(1):E188-E193. doi:10.1073/pnas.1315541111 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. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.1315541111 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.” PNAS. National Academy of Sciences, 2014. https://doi.org/10.1073/pnas.1315541111. ieee: W. Wang et al., “Distinct cerebellar engrams in short-term and long-term motor learning,” PNAS, 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. mla: Wang, Wen, et al. “Distinct Cerebellar Engrams in Short-Term and Long-Term Motor Learning.” PNAS, vol. 111, no. 1, National Academy of Sciences, 2014, pp. E188–93, doi:10.1073/pnas.1315541111. 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. date_created: 2018-12-11T11:54:43Z date_published: 2014-01-07T00:00:00Z date_updated: 2021-01-12T06:54:05Z day: '07' department: - _id: RySh doi: 10.1073/pnas.1315541111 intvolume: ' 111' issue: '1' language: - iso: eng main_file_link: - open_access: '1' url: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890858/ month: '01' oa: 1 oa_version: Submitted Version page: E188 - E193 publication: PNAS publication_status: published publisher: National Academy of Sciences publist_id: '5174' scopus_import: 1 status: public title: Distinct cerebellar engrams in short-term and long-term motor learning type: journal_article user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87 volume: 111 year: '2014' ... --- _id: '1919' 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. 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.). author: - first_name: Wajeeha full_name: Aziz, Wajeeha last_name: Aziz - first_name: Wen full_name: Wang, Wen last_name: Wang - first_name: Sebnem full_name: Kesaf, Sebnem id: 401AB46C-F248-11E8-B48F-1D18A9856A87 last_name: Kesaf - first_name: Alsayed full_name: Mohamed, Alsayed last_name: Mohamed - first_name: Yugo full_name: Fukazawa, Yugo last_name: Fukazawa - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: 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. PNAS. 2014;111(1):E194-E202. doi:10.1073/pnas.1303317110 apa: 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. National Academy of Sciences. https://doi.org/10.1073/pnas.1303317110 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.” PNAS. National Academy of Sciences, 2014. https://doi.org/10.1073/pnas.1303317110. 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,” PNAS, 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. mla: Aziz, Wajeeha, et al. “Distinct Kinetics of Synaptic Structural Plasticity, Memory Formation, and Memory Decay in Massed and Spaced Learning.” PNAS, vol. 111, no. 1, National Academy of Sciences, 2014, pp. E194–202, doi:10.1073/pnas.1303317110. short: W. Aziz, W. Wang, S. Kesaf, A. Mohamed, Y. Fukazawa, R. Shigemoto, PNAS 111 (2014) E194–E202. date_created: 2018-12-11T11:54:43Z date_published: 2014-01-07T00:00:00Z date_updated: 2021-01-12T06:54:04Z day: '07' department: - _id: RySh doi: 10.1073/pnas.1303317110 intvolume: ' 111' issue: '1' language: - iso: eng main_file_link: - open_access: '1' url: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890840/ month: '01' oa: 1 oa_version: Submitted Version page: E194 - E202 publication: PNAS publication_status: published publisher: National Academy of Sciences publist_id: '5175' scopus_import: 1 status: public title: Distinct kinetics of synaptic structural plasticity, memory formation, and memory decay in massed and spaced learning type: journal_article user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87 volume: 111 year: '2014' ... --- _id: '1933' 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. author: - first_name: Jun full_name: Hatakeyama, Jun last_name: Hatakeyama - first_name: Yoshio full_name: Wakamatsu, Yoshio last_name: Wakamatsu - first_name: Akira full_name: Nagafuchi, Akira last_name: Nagafuchi - first_name: Ryoichiro full_name: Kageyama, Ryoichiro last_name: Kageyama - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Kenji full_name: Shimamura, Kenji last_name: Shimamura citation: 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. Development. 2014;141(8):1671-1682. doi:10.1242/dev.102988 apa: 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. Company of Biologists. https://doi.org/10.1242/dev.102988 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.” Development. Company of Biologists, 2014. https://doi.org/10.1242/dev.102988. 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,” Development, vol. 141, no. 8. Company of Biologists, pp. 1671–1682, 2014. 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. mla: Hatakeyama, Jun, et al. “Cadherin-Based Adhesions in the Apical Endfoot Are Required for Active Notch Signaling to Control Neurogenesis in Vertebrates.” Development, vol. 141, no. 8, Company of Biologists, 2014, pp. 1671–82, doi:10.1242/dev.102988. short: J. Hatakeyama, Y. Wakamatsu, A. Nagafuchi, R. Kageyama, R. Shigemoto, K. Shimamura, Development 141 (2014) 1671–1682. date_created: 2018-12-11T11:54:47Z date_published: 2014-04-01T00:00:00Z date_updated: 2021-01-12T06:54:10Z day: '01' department: - _id: RySh doi: 10.1242/dev.102988 intvolume: ' 141' issue: '8' language: - iso: eng month: '04' oa_version: None page: 1671 - 1682 publication: Development publication_status: published publisher: Company of Biologists publist_id: '5161' quality_controlled: '1' scopus_import: 1 status: public title: Cadherin-based adhesions in the apical endfoot are required for active Notch signaling to control neurogenesis in vertebrates type: journal_article user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87 volume: 141 year: '2014' ... --- _id: '2018' abstract: - lang: eng 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. 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 article_type: original author: - first_name: Hiroshi full_name: Matsukawa, Hiroshi last_name: Matsukawa - first_name: Sachiko full_name: Akiyoshi Nishimura, Sachiko last_name: Akiyoshi Nishimura - first_name: Qi full_name: Zhang, Qi last_name: Zhang - first_name: Rafael full_name: Luján, Rafael last_name: Luján - first_name: Kazuhiko full_name: Yamaguchi, Kazuhiko last_name: Yamaguchi - first_name: Hiromichi full_name: Goto, Hiromichi last_name: Goto - first_name: Kunio full_name: Yaguchi, Kunio last_name: Yaguchi - first_name: Tsutomu full_name: Hashikawa, Tsutomu last_name: Hashikawa - first_name: Chie full_name: Sano, Chie last_name: Sano - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Toshiaki full_name: Nakashiba, Toshiaki last_name: Nakashiba - first_name: Shigeyoshi full_name: Itohara, Shigeyoshi last_name: Itohara citation: ama: Matsukawa H, Akiyoshi Nishimura S, Zhang Q, et al. Netrin-G/NGL complexes encode functional synaptic diversification. Journal of Neuroscience. 2014;34(47):15779-15792. doi:10.1523/JNEUROSCI.1141-14.2014 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. Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.1141-14.2014 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.” Journal of Neuroscience. Society for Neuroscience, 2014. https://doi.org/10.1523/JNEUROSCI.1141-14.2014. ieee: H. Matsukawa et al., “Netrin-G/NGL complexes encode functional synaptic diversification,” Journal of Neuroscience, vol. 34, no. 47. Society for Neuroscience, pp. 15779–15792, 2014. 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. mla: Matsukawa, Hiroshi, et al. “Netrin-G/NGL Complexes Encode Functional Synaptic Diversification.” Journal of Neuroscience, vol. 34, no. 47, Society for Neuroscience, 2014, pp. 15779–92, doi:10.1523/JNEUROSCI.1141-14.2014. 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. date_created: 2018-12-11T11:55:14Z date_published: 2014-11-19T00:00:00Z date_updated: 2022-05-24T08:54:54Z day: '19' ddc: - '570' department: - _id: RySh doi: 10.1523/JNEUROSCI.1141-14.2014 external_id: pmid: - '25411505' file: - access_level: open_access checksum: 6913e9bc26e9fc1c0441a739a4199229 content_type: application/pdf creator: dernst date_created: 2022-05-24T08:41:41Z date_updated: 2022-05-24T08:41:41Z file_id: '11410' file_name: 2014_JournNeuroscience_Matsukawa.pdf file_size: 3963728 relation: main_file success: 1 file_date_updated: 2022-05-24T08:41:41Z has_accepted_license: '1' intvolume: ' 34' issue: '47' language: - iso: eng month: '11' oa: 1 oa_version: Published Version page: 15779 - 15792 pmid: 1 publication: Journal of Neuroscience publication_identifier: eissn: - 1529-2401 issn: - 0270-6474 publication_status: published publisher: Society for Neuroscience publist_id: '5054' quality_controlled: '1' scopus_import: '1' status: public title: Netrin-G/NGL complexes encode functional synaptic diversification type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 34 year: '2014' ... --- _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. acknowledgement: "National Institutes of Health (NIH) Grant Number: 1R01DC013048‐0; Biotechnology and Biological Sciences Research Council, UK Grant Number: BB/J015938/1\r\n" author: - first_name: Maía full_name: Rubio, Maía last_name: Rubio - first_name: Yugo full_name: Fukazawa, Yugo last_name: Fukazawa - first_name: Naomi full_name: Kamasawa, Naomi last_name: Kamasawa - first_name: Cheryl full_name: Clarkson, Cheryl last_name: Clarkson - first_name: Elek full_name: Molnár, Elek last_name: Molnár - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: 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. Journal of Comparative Neurology. 2014;522(18):4023-4042. doi:10.1002/cne.23654 apa: 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. Wiley-Blackwell. https://doi.org/10.1002/cne.23654 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.” Journal of Comparative Neurology. Wiley-Blackwell, 2014. https://doi.org/10.1002/cne.23654. 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,” Journal of Comparative Neurology, vol. 522, no. 18. Wiley-Blackwell, pp. 4023–4042, 2014. 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. mla: Rubio, Maía, et al. “Target- and Input-Dependent Organization of AMPA and NMDA Receptors in Synaptic Connections of the Cochlear Nucleus.” Journal of Comparative Neurology, vol. 522, no. 18, Wiley-Blackwell, 2014, pp. 4023–42, doi:10.1002/cne.23654. short: M. Rubio, Y. Fukazawa, N. Kamasawa, C. Clarkson, E. Molnár, R. Shigemoto, Journal of Comparative Neurology 522 (2014) 4023–4042. date_created: 2018-12-11T11:55:30Z date_published: 2014-07-29T00:00:00Z date_updated: 2021-01-12T06:55:05Z day: '29' department: - _id: RySh doi: 10.1002/cne.23654 intvolume: ' 522' issue: '18' language: - iso: eng main_file_link: - open_access: '1' url: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198489/ month: '07' oa: 1 oa_version: Submitted Version page: 4023 - 4042 publication: Journal of Comparative Neurology publication_status: published publisher: Wiley-Blackwell publist_id: '4974' quality_controlled: '1' scopus_import: 1 status: public title: Target- and input-dependent organization of AMPA and NMDA receptors in synaptic connections of the cochlear nucleus type: journal_article user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87 volume: 522 year: '2014' ... --- _id: '2241' 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.' author: - first_name: Kaoru full_name: Beppu, Kaoru last_name: Beppu - first_name: Takuya full_name: Sasaki, Takuya last_name: Sasaki - first_name: Kenji full_name: Tanaka, Kenji last_name: Tanaka - first_name: Akihiro full_name: Yamanaka, Akihiro last_name: Yamanaka - first_name: Yugo full_name: Fukazawa, Yugo last_name: Fukazawa - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Ko full_name: Matsui, Ko last_name: Matsui citation: ama: Beppu K, Sasaki T, Tanaka K, et al. Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage. Neuron. 2014;81(2):314-320. doi:10.1016/j.neuron.2013.11.011 apa: 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. Elsevier. https://doi.org/10.1016/j.neuron.2013.11.011 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.” Neuron. Elsevier, 2014. https://doi.org/10.1016/j.neuron.2013.11.011. ieee: K. Beppu et al., “Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage,” Neuron, 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. mla: Beppu, Kaoru, et al. “Optogenetic Countering of Glial Acidosis Suppresses Glial Glutamate Release and Ischemic Brain Damage.” Neuron, vol. 81, no. 2, Elsevier, 2014, pp. 314–20, doi:10.1016/j.neuron.2013.11.011. short: K. Beppu, T. Sasaki, K. Tanaka, A. Yamanaka, Y. Fukazawa, R. Shigemoto, K. Matsui, Neuron 81 (2014) 314–320. date_created: 2018-12-11T11:56:31Z date_published: 2014-01-22T00:00:00Z date_updated: 2021-01-12T06:56:14Z day: '22' department: - _id: RySh doi: 10.1016/j.neuron.2013.11.011 intvolume: ' 81' issue: '2' language: - iso: eng month: '01' oa_version: None page: 314 - 320 publication: Neuron publication_identifier: issn: - '08966273' publication_status: published publisher: Elsevier publist_id: '4715' quality_controlled: '1' scopus_import: 1 status: public title: Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage type: journal_article user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87 volume: 81 year: '2014' ...