--- DOAJ_listed: '1' OA_place: publisher OA_type: gold _id: '21502' abstract: - lang: eng text: The mammalian brain stores glucose, the main circulating energy substrate, as glycogen. In rodents, the cerebellum contains relatively high glycogen levels, yet its cellular and subcellular distribution remains poorly defined. Using monoclonal antibodies against glycogen, we examined its distribution in the mouse cerebellar cortex. Glycogen was predominantly localized to Bergmann glia (BG) processes in the molecular layer and was also detected in Purkinje cells (PCs), the principal cerebellar neurons. To assess the functional significance of cerebellar glycogen, we analyzed behavior in mice lacking glycogen synthase 1 (Gys1) in BG or PCs using a floxed Gys1 line. Gys1 deficiency in either PCs or GFAP-positive cells reduced anxiety-like behavior, whereas combined deletion caused PC degeneration and ataxia. These findings reveal a critical role for glycogen metabolism in both astrocytes and neurons in cerebellar function. acknowledgement: This work was supported by the Novo Nordisk Foundation (NNFOC0058058, H. Hirase), the Danmarks Frie Forskningsfond (0134-00107B and 5283-00069A, H.Hirase), the Lundbeck Foundation, Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAKENHI) program (22K06454/24H01221, A.K.; 23K27482, H.Hirai), the Japan Agency for Medical Research and Development (AMED) Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) (JP21dm0207111, H. Hirai), AMED Brain/MINDS 2.0 (JP23wm0625001 and JP24wm0625103, H. Hirai), and grants from the Spanish Ministerio de Ciencia e Innovación (MCIU/FEDER/AEI) (PID2020-118699 GB-100, J.D.) and the Fundación Ramón Areces (J.D.). Sonam Akther has been supported by the RIKEN IPA fellowship. We are thankful to Dr. Yuki Oe for his support in the initial stage of this study and to Dan Xue for his help with the graphical abstract. We thank Dr. Pia Weikop for providing CTN research infrastructure. The authors declare no competing financial interests. article_number: '115192' article_processing_charge: Yes article_type: original author: - first_name: Sonam full_name: Akther, Sonam last_name: Akther - first_name: Ashley Bomin full_name: Lee, Ashley Bomin last_name: Lee - first_name: Ayumu full_name: Konno, Ayumu last_name: Konno - first_name: Antonis full_name: Asiminas, Antonis last_name: Asiminas - first_name: Marta full_name: Vittani, Marta last_name: Vittani - first_name: Tsuneko full_name: Mishima, Tsuneko last_name: Mishima - first_name: Hirokazu full_name: Hirai, Hirokazu last_name: Hirai - first_name: Claire Francesca full_name: Meehan, Claire Francesca last_name: Meehan - first_name: Jordi full_name: Duran, Jordi last_name: Duran - first_name: Joan full_name: Guinovart, Joan last_name: Guinovart - first_name: Hitoshi full_name: Ashida, Hitoshi last_name: Ashida - first_name: Tsuyoshi full_name: Morita, Tsuyoshi last_name: Morita - first_name: Otto full_name: Baba, Otto last_name: Baba - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Maiken full_name: Nedergaard, Maiken last_name: Nedergaard - first_name: Hajime full_name: Hirase, Hajime last_name: Hirase citation: ama: Akther S, Lee AB, Konno A, et al. Distribution and functional significance of rodent cerebellar glycogen. iScience. 2026;29(4). doi:10.1016/j.isci.2026.115192 apa: Akther, S., Lee, A. B., Konno, A., Asiminas, A., Vittani, M., Mishima, T., … Hirase, H. (2026). Distribution and functional significance of rodent cerebellar glycogen. IScience. Elsevier. https://doi.org/10.1016/j.isci.2026.115192 chicago: Akther, Sonam, Ashley Bomin Lee, Ayumu Konno, Antonis Asiminas, Marta Vittani, Tsuneko Mishima, Hirokazu Hirai, et al. “Distribution and Functional Significance of Rodent Cerebellar Glycogen.” IScience. Elsevier, 2026. https://doi.org/10.1016/j.isci.2026.115192. ieee: S. Akther et al., “Distribution and functional significance of rodent cerebellar glycogen,” iScience, vol. 29, no. 4. Elsevier, 2026. ista: Akther S, Lee AB, Konno A, Asiminas A, Vittani M, Mishima T, Hirai H, Meehan CF, Duran J, Guinovart J, Ashida H, Morita T, Baba O, Shigemoto R, Nedergaard M, Hirase H. 2026. Distribution and functional significance of rodent cerebellar glycogen. iScience. 29(4), 115192. mla: Akther, Sonam, et al. “Distribution and Functional Significance of Rodent Cerebellar Glycogen.” IScience, vol. 29, no. 4, 115192, Elsevier, 2026, doi:10.1016/j.isci.2026.115192. short: S. Akther, A.B. Lee, A. Konno, A. Asiminas, M. Vittani, T. Mishima, H. Hirai, C.F. Meehan, J. Duran, J. Guinovart, H. Ashida, T. Morita, O. Baba, R. Shigemoto, M. Nedergaard, H. Hirase, IScience 29 (2026). date_created: 2026-03-29T22:07:07Z date_published: 2026-03-17T00:00:00Z date_updated: 2026-03-30T06:20:06Z day: '17' department: - _id: RySh doi: 10.1016/j.isci.2026.115192 external_id: pmid: - '41890976' intvolume: ' 29' issue: '4' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1016/j.isci.2026.115192 month: '03' oa: 1 oa_version: Published Version pmid: 1 publication: iScience publication_identifier: eissn: - 2589-0042 publication_status: epub_ahead publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Distribution and functional significance of rodent cerebellar glycogen type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 29 year: '2026' ... --- OA_place: publisher OA_type: gold PlanS_conform: '1' _id: '20659' abstract: - lang: eng text: "Metabotropic GABA (GABAB) receptors have modulatory functions on neuronal excitability and\r\nneurotransmitter release. To fulfil these functions, GABAB receptors form macromolecular signaling complexes with G proteins, effectors, and other associated proteins. Here we investigated the postnatal development of GABAB receptors (GABAB1 and GABAB2 subunits) in mouse brain, focusing on potential similarities in the spatial and temporal expression pattern\r\nof their associated proteins CaV2.1, Gαo, Gβ5, and RGS7, using histoblots, immunofluorescence, and immunoelectron microscopic techniques. At all ages analyzed, histoblot showed that the six proteins were widely expressed in the brain, with mostly an\r\noverlapping pattern throughout postnatal development. In the hippocampus, immunoelectron microscopy and quantitative analysis of immunoparticles for GABAB1, GABAB2, Gαo, Gβ5, and RGS7 revealed their progressive enrichment around excitatory synapses on dendritic spines of CA1 pyramidal cells toward P15. At presynaptic sites, GABAB receptors colocalize with\r\nCaV2.1, Gαo, Gβ5, and RGS7 in the active zone and extrasynaptic membranes of axon terminals, establishing synapses on dendritic spines of CA1 pyramidal cells. In the cerebellum, double immunofluorescence at P7 and P10 revealed the colocalization of GABAB1 and CaV2.1\r\nin the whole dendritic tree of developing Purkinje cells. Immunoelectron microscopy at P15 showed that GABAB1, GABAB2, CaV2.1, Gαo, Gβ5, and RGS7 are distributed along the dendritic surface of Purkinje cells, enriched close to excitatory synapses in spines.\r\nAltogether, these data suggest that macromolecular complexes composed of GABAB1 /GABAB2/CaV2.1/ Gαo/Gβ5/RGS7 are pre-assembled during key stages of postnatal development in hippocampal and cerebellar neurons." acknowledgement: We thank Ms. Diane Latawiec for the English revision of the manuscript. Funding sources were the Spanish Ministerio de Economía y Competitividad, and Junta de Comunidades de CastillaLa Mancha (Spain). Grants PID2021-125875OB-I00 funded by MCIN/AEI/ 10.13039/501100011033 and “ERDF A way of making Europe” to RL. This work was also supported by Castilla-La Mancha Regional Government and the European Regional Development Fund (SBPLY/21/180501/000064) and the Universidad de Castilla-La Mancha (2023-GRIN-34187) to RL. article_processing_charge: Yes article_type: original author: - first_name: Carolina full_name: Aguado, Carolina last_name: Aguado - first_name: Rocío full_name: Alfaro-Ruiz, Rocío last_name: Alfaro-Ruiz - first_name: María Llanos full_name: Martínez-Poyato, María Llanos last_name: Martínez-Poyato - first_name: Ana Esther full_name: Moreno-Martínez, Ana Esther last_name: Moreno-Martínez - first_name: Sebastián full_name: García-Madrona, Sebastián last_name: García-Madrona - first_name: Alberto full_name: Roldán-Sastre, Alberto last_name: Roldán-Sastre - first_name: Pablo full_name: Alonso-Gómez, Pablo last_name: Alonso-Gómez - first_name: Miriam full_name: Fernández, Miriam last_name: Fernández - first_name: Ricardo full_name: Puertas-Avendaño, Ricardo last_name: Puertas-Avendaño - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Kirill A. full_name: Martemyanov, Kirill A. last_name: Martemyanov - first_name: Rafael full_name: Luján, Rafael last_name: Luján citation: ama: Aguado C, Alfaro-Ruiz R, Martínez-Poyato ML, et al. Developmental regulation of GABAB receptors and downstream molecules in the mouse brain. Histology and Histopathology. 2025;40(12):1967-1984. doi:10.14670/HH-18-970 apa: Aguado, C., Alfaro-Ruiz, R., Martínez-Poyato, M. L., Moreno-Martínez, A. E., García-Madrona, S., Roldán-Sastre, A., … Luján, R. (2025). Developmental regulation of GABAB receptors and downstream molecules in the mouse brain. Histology and Histopathology. Sercrisma International. https://doi.org/10.14670/HH-18-970 chicago: Aguado, Carolina, Rocío Alfaro-Ruiz, María Llanos Martínez-Poyato, Ana Esther Moreno-Martínez, Sebastián García-Madrona, Alberto Roldán-Sastre, Pablo Alonso-Gómez, et al. “Developmental Regulation of GABAB Receptors and Downstream Molecules in the Mouse Brain.” Histology and Histopathology. Sercrisma International, 2025. https://doi.org/10.14670/HH-18-970. ieee: C. Aguado et al., “Developmental regulation of GABAB receptors and downstream molecules in the mouse brain,” Histology and Histopathology, vol. 40, no. 12. Sercrisma International, pp. 1967–1984, 2025. ista: Aguado C, Alfaro-Ruiz R, Martínez-Poyato ML, Moreno-Martínez AE, García-Madrona S, Roldán-Sastre A, Alonso-Gómez P, Fernández M, Puertas-Avendaño R, Shigemoto R, Martemyanov KA, Luján R. 2025. Developmental regulation of GABAB receptors and downstream molecules in the mouse brain. Histology and Histopathology. 40(12), 1967–1984. mla: Aguado, Carolina, et al. “Developmental Regulation of GABAB Receptors and Downstream Molecules in the Mouse Brain.” Histology and Histopathology, vol. 40, no. 12, Sercrisma International, 2025, pp. 1967–84, doi:10.14670/HH-18-970. short: C. Aguado, R. Alfaro-Ruiz, M.L. Martínez-Poyato, A.E. Moreno-Martínez, S. García-Madrona, A. Roldán-Sastre, P. Alonso-Gómez, M. Fernández, R. Puertas-Avendaño, R. Shigemoto, K.A. Martemyanov, R. Luján, Histology and Histopathology 40 (2025) 1967–1984. date_created: 2025-11-23T23:01:37Z date_published: 2025-12-01T00:00:00Z date_updated: 2025-11-24T10:24:35Z day: '01' ddc: - '570' department: - _id: RySh doi: 10.14670/HH-18-970 external_id: pmid: - '40704638' file: - access_level: open_access checksum: 779d67434400c0f94af42c35ba21c672 content_type: application/pdf creator: dernst date_created: 2025-11-24T10:23:39Z date_updated: 2025-11-24T10:23:39Z file_id: '20677' file_name: 2025_HistologyHistopathology_Aguado.pdf file_size: 18093266 relation: main_file success: 1 file_date_updated: 2025-11-24T10:23:39Z has_accepted_license: '1' intvolume: ' 40' issue: '12' language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '12' oa: 1 oa_version: Published Version page: 1967-1984 pmid: 1 publication: Histology and Histopathology publication_identifier: eissn: - 1699-5848 publication_status: published publisher: Sercrisma International quality_controlled: '1' scopus_import: '1' status: public title: Developmental regulation of GABAB receptors and downstream molecules in the mouse brain 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: 40 year: '2025' ... --- DOAJ_listed: '1' OA_place: publisher OA_type: gold _id: '17293' abstract: - lang: eng text: Voltage-gated CaV2.1 (P/Q-type) Ca2+ channels play a crucial role in regulating neurotransmitter release, thus contributing to synaptic plasticity and to processes such as learning and memory. Despite their recognized importance in neural function, there is limited information on their potential involvement in neurodegenerative conditions such as Alzheimer's disease (AD). Here, we aimed to explore the impact of AD pathology on the density and nanoscale compartmentalization of CaV2.1 channels in the hippocampus in association with GABAB receptors. Histoblotting experiments showed that the density of CaV2.1 channel was significantly reduced in the hippocampus of APP/PS1 mice in a laminar-dependent manner. CaV2.1 channel was enriched in the active zone of the axon terminals and was present at a very low density over the surface of dendritic tree of the CA1 pyramidal cells, as shown by quantitative SDS-digested freeze-fracture replica labelling (SDS-FRL). In APP/PS1 mice, the density of CaV2.1 channel in the active zone was significantly reduced in the strata radiatum and lacunosum-moleculare, while it remained unaltered in the stratum oriens. The decline in Cav2.1 channel density was found to be associated with a corresponding impairment in the GABAergic synaptic function, as evidenced by electrophysiological experiments carried out in the hippocampus of APP/PS1 mice. Remarkably, double SDS-FRL showed a co-clustering of CaV2.1 channel and GABAB1 receptor in nanodomains (~40–50 nm) in wild type mice, while in APP/PS1 mice this nanoarchitecture was absent. Together, these findings suggest that the AD pathology-induced reduction in CaV2.1 channel density and CaV2.1-GABAB1 de-clustering may play a role in the synaptic transmission alterations shown in the AD hippocampus. Therefore, uncovering these layer-dependent changes in P/Q calcium currents associated with AD pathology can benefit the development of future strategies for AD management. acknowledgement: "Funding sources were Spanish Ministerio de Economía y Competitividad, Junta de Comunidades de Castilla-La Mancha (Spain), Life Science Innovation Center at University of Fukui and German Research Foundation.\r\nGrants RTI2018-095812-B-I00 and PID2021-125875OB-I00 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe” to Rafael Luján. This study was also supported by a grant from Junta de Comunidades de Castilla-La Mancha (SBPLY/17/180501/000229 and SBPLY/21/180501/000064) and Universidad de Castilla-La Mancha (2023-GRIN-34187) to Rafael Luján, and Life Science Innovation Center (Research and Education Program for Life Science) at University of Fukui and JSPS KAKENHI Grant Numbers 16H04662, 17K19446, 18H05120 to Yugo Fukazawa and Margarita Salas fellowship from Ministerio de Universidades and Universidad de Castilla-La Mancha to Alejandro Martín-Belmonte. German Research Foundation (DFG FOR 2143) and BIOSS-2 to Akos Kulik." article_number: e13279 article_processing_charge: Yes article_type: original author: - first_name: Alejandro full_name: Martín‐Belmonte, Alejandro last_name: Martín‐Belmonte - first_name: Carolina full_name: Aguado, Carolina last_name: Aguado - first_name: Rocío full_name: Alfaro‐Ruiz, Rocío last_name: Alfaro‐Ruiz - first_name: Akos full_name: Kulik, Akos last_name: Kulik - first_name: Luis full_name: de la Ossa, Luis last_name: de la Ossa - first_name: Ana Esther full_name: Moreno‐Martínez, Ana Esther last_name: Moreno‐Martínez - first_name: Samuel full_name: Alberquilla, Samuel last_name: Alberquilla - first_name: Lucía full_name: García‐Carracedo, Lucía last_name: García‐Carracedo - first_name: Miriam full_name: Fernández, Miriam last_name: Fernández - first_name: Ana full_name: Fajardo‐Serrano, Ana last_name: Fajardo‐Serrano - first_name: Ester full_name: Aso, Ester last_name: Aso - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Eduardo D. full_name: Martín, Eduardo D. last_name: Martín - first_name: Yugo full_name: Fukazawa, Yugo last_name: Fukazawa - first_name: Francisco full_name: Ciruela, Francisco last_name: Ciruela - first_name: Rafael full_name: Luján, Rafael last_name: Luján citation: ama: 'Martín‐Belmonte A, Aguado C, Alfaro‐Ruiz R, et al. Nanoarchitecture of CaV>2.1 channels and GABAB receptors in the mouse hippocampus: Impact of APP/PS1 pathology. Brain Pathology. 2025;35(2). doi:10.1111/bpa.13279' apa: 'Martín‐Belmonte, A., Aguado, C., Alfaro‐Ruiz, R., Kulik, A., de la Ossa, L., Moreno‐Martínez, A. E., … Luján, R. (2025). Nanoarchitecture of CaV>2.1 channels and GABAB receptors in the mouse hippocampus: Impact of APP/PS1 pathology. Brain Pathology. Wiley. https://doi.org/10.1111/bpa.13279' chicago: 'Martín‐Belmonte, Alejandro, Carolina Aguado, Rocío Alfaro‐Ruiz, Akos Kulik, Luis de la Ossa, Ana Esther Moreno‐Martínez, Samuel Alberquilla, et al. “Nanoarchitecture of CaV>2.1 Channels and GABAB Receptors in the Mouse Hippocampus: Impact of APP/PS1 Pathology.” Brain Pathology. Wiley, 2025. https://doi.org/10.1111/bpa.13279.' ieee: 'A. Martín‐Belmonte et al., “Nanoarchitecture of CaV>2.1 channels and GABAB receptors in the mouse hippocampus: Impact of APP/PS1 pathology,” Brain Pathology, vol. 35, no. 2. Wiley, 2025.' ista: 'Martín‐Belmonte A, Aguado C, Alfaro‐Ruiz R, Kulik A, de la Ossa L, Moreno‐Martínez AE, Alberquilla S, García‐Carracedo L, Fernández M, Fajardo‐Serrano A, Aso E, Shigemoto R, Martín ED, Fukazawa Y, Ciruela F, Luján R. 2025. Nanoarchitecture of CaV>2.1 channels and GABAB receptors in the mouse hippocampus: Impact of APP/PS1 pathology. Brain Pathology. 35(2), e13279.' mla: 'Martín‐Belmonte, Alejandro, et al. “Nanoarchitecture of CaV>2.1 Channels and GABAB Receptors in the Mouse Hippocampus: Impact of APP/PS1 Pathology.” Brain Pathology, vol. 35, no. 2, e13279, Wiley, 2025, doi:10.1111/bpa.13279.' short: A. Martín‐Belmonte, C. Aguado, R. Alfaro‐Ruiz, A. Kulik, L. de la Ossa, A.E. Moreno‐Martínez, S. Alberquilla, L. García‐Carracedo, M. Fernández, A. Fajardo‐Serrano, E. Aso, R. Shigemoto, E.D. Martín, Y. Fukazawa, F. Ciruela, R. Luján, Brain Pathology 35 (2025). date_created: 2024-07-22T07:48:20Z date_published: 2025-03-01T00:00:00Z date_updated: 2025-05-19T13:58:12Z day: '01' ddc: - '570' department: - _id: RySh doi: 10.1111/bpa.13279 external_id: isi: - '001250034200001' pmid: - '38887180' file: - access_level: open_access checksum: 75a172800ab2e949abb66fba97cf70f0 content_type: application/pdf creator: dernst date_created: 2025-04-16T09:56:08Z date_updated: 2025-04-16T09:56:08Z file_id: '19582' file_name: 2025_BrainPathology_MartinBelmonte.pdf file_size: 8767863 relation: main_file success: 1 file_date_updated: 2025-04-16T09:56:08Z has_accepted_license: '1' intvolume: ' 35' isi: 1 issue: '2' language: - iso: eng license: https://creativecommons.org/licenses/by-nc-nd/4.0/ month: '03' oa: 1 oa_version: Published Version pmid: 1 publication: Brain Pathology publication_identifier: eissn: - 1750-3639 issn: - 1015-6305 publication_status: published publisher: Wiley quality_controlled: '1' scopus_import: '1' status: public title: 'Nanoarchitecture of CaV>2.1 channels and GABAB receptors in the mouse hippocampus: Impact of APP/PS1 pathology' tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 35 year: '2025' ... --- _id: '18052' abstract: - lang: eng text: Sodium dodecyl sulfate-digested freeze-fracture replica labeling (SDS-FRL) is an electron microscope (EM) sample preparation technique which allows for high-resolution visualization of membrane proteins with high sensitivity. However, image acquisition of specific replica profiles such as synapses in a large field of EM view needs a valid experience and a long time for manual searching. Here, we describe how to utilize deep learning for automatizing image acquisition of specific profiles of interest in replica samples. This protocol facilitates the labor-intensive collection of EM images, in particular for rare profiles. We provide instructions for using SerialEM image acquisition software in conjunction with object detection by our newly developed deep learning software DarEM, to automatically acquire tilt series of all synapses in a selected region. We then show how to perform a mostly automated analysis of gold particle labeling in the acquired images by utilizing Darea software. acknowledged_ssus: - _id: EM-Fac acknowledgement: This research was supported by the European Research Council Advanced Grant 694539 to RS and by the Scientific Service Units of IST Austria through resources provided by the Electron Microscopy Facility. alternative_title: - Neuromethods article_processing_charge: No author: - first_name: David full_name: Kleindienst, David id: 42E121A4-F248-11E8-B48F-1D18A9856A87 last_name: Kleindienst - first_name: Tommaso full_name: Costanzo, Tommaso id: D93824F4-D9BA-11E9-BB12-F207E6697425 last_name: Costanzo orcid: 0000-0001-9732-3815 - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: ama: 'Kleindienst D, Costanzo T, Shigemoto R. Automated Imaging and Analysis of Synapses in Freeze-Fracture Replica Samples with Deep Learning. In: Lübke JHR, Rollenhagen A, eds. New Aspects in Analyzing the Synaptic Organization of the Brain. 1st ed. New York: Springer Nature; 2024:123-137. doi:10.1007/978-1-0716-4019-7_8' apa: 'Kleindienst, D., Costanzo, T., & Shigemoto, R. (2024). Automated Imaging and Analysis of Synapses in Freeze-Fracture Replica Samples with Deep Learning. In J. H. R. Lübke & A. Rollenhagen (Eds.), New Aspects in Analyzing the Synaptic Organization of the Brain (1st ed., pp. 123–137). New York: Springer Nature. https://doi.org/10.1007/978-1-0716-4019-7_8' chicago: 'Kleindienst, David, Tommaso Costanzo, and Ryuichi Shigemoto. “Automated Imaging and Analysis of Synapses in Freeze-Fracture Replica Samples with Deep Learning.” In New Aspects in Analyzing the Synaptic Organization of the Brain, edited by Joachim H.R. Lübke and Astrid Rollenhagen, 1st ed., 123–37. New York: Springer Nature, 2024. https://doi.org/10.1007/978-1-0716-4019-7_8.' ieee: 'D. Kleindienst, T. Costanzo, and R. Shigemoto, “Automated Imaging and Analysis of Synapses in Freeze-Fracture Replica Samples with Deep Learning,” in New Aspects in Analyzing the Synaptic Organization of the Brain, 1st ed., J. H. R. Lübke and A. Rollenhagen, Eds. New York: Springer Nature, 2024, pp. 123–137.' ista: 'Kleindienst D, Costanzo T, Shigemoto R. 2024.Automated Imaging and Analysis of Synapses in Freeze-Fracture Replica Samples with Deep Learning. In: New Aspects in Analyzing the Synaptic Organization of the Brain. Neuromethods, , 123–137.' mla: Kleindienst, David, et al. “Automated Imaging and Analysis of Synapses in Freeze-Fracture Replica Samples with Deep Learning.” New Aspects in Analyzing the Synaptic Organization of the Brain, edited by Joachim H.R. Lübke and Astrid Rollenhagen, 1st ed., Springer Nature, 2024, pp. 123–37, doi:10.1007/978-1-0716-4019-7_8. short: D. Kleindienst, T. Costanzo, R. Shigemoto, in:, J.H.R. Lübke, A. Rollenhagen (Eds.), New Aspects in Analyzing the Synaptic Organization of the Brain, 1st ed., Springer Nature, New York, 2024, pp. 123–137. corr_author: '1' date_created: 2024-09-10T12:32:38Z date_published: 2024-08-27T00:00:00Z date_updated: 2025-04-14T07:27:15Z day: '27' department: - _id: EM-Fac - _id: RySh doi: 10.1007/978-1-0716-4019-7_8 ec_funded: 1 edition: '1' editor: - first_name: 'Joachim H.R. ' full_name: 'Lübke, Joachim H.R. ' last_name: Lübke - first_name: Astrid full_name: Rollenhagen, Astrid last_name: Rollenhagen language: - iso: eng month: '08' oa_version: None page: 123-137 place: New York project: - _id: 25CA28EA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '694539' name: 'In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour' publication: New Aspects in Analyzing the Synaptic Organization of the Brain publication_identifier: eisbn: - '9781071640197' eissn: - 1940-6045 isbn: - '9781071640180' issn: - 0893-2336 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Automated Imaging and Analysis of Synapses in Freeze-Fracture Replica Samples with Deep Learning type: book_chapter user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2024' ... --- _id: '15385' abstract: - lang: eng text: "Relevant information about the data can be found in the 'Readme_Data.txt' file. \r\nA previous version of the publication can be found on BioRxiv: https://www.biorxiv.org/content/10.1101/2022.10.11.511691v4\r\nand published in Plos Biology (2024)" acknowledged_ssus: - _id: PreCl - _id: M-Shop - _id: LifeSc - _id: Bio acknowledgement: 'We thank Armel Nicolas, Bella Bruszel and Ewelina Dutkiewicz from the ISTA Mass Spectrometry Service (Lab Services Facilities) for all Proteomics work, including samples preparation, LC/MS data acquisition, searches and data evaluation. We thank Prof. Peter Jonas for his suggestion on the involvement of potassium channels and members of the Neuroethology group for their comments on the manuscript. Katalin Szigeti and Julie Murmann for experimental help. This research was supported by the Scientific Service Units of ISTA through resources provided by the Lab Support Facility, the Imaging and Optics Facility, the Machine Shop Unit and the Preclinical Facility, especially Freyja Langer and Michael Schunn. ' article_processing_charge: No author: - first_name: Laura full_name: Burnett, Laura id: 3B717F68-F248-11E8-B48F-1D18A9856A87 last_name: Burnett orcid: 0000-0002-8937-410X - first_name: Peter full_name: Koppensteiner, Peter id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87 last_name: Koppensteiner orcid: 0000-0002-3509-1948 - first_name: Olga full_name: Symonova, Olga id: 3C0C7BC6-F248-11E8-B48F-1D18A9856A87 last_name: Symonova orcid: 0000-0003-2012-9947 - first_name: Tomas full_name: Masson, Tomas id: 93ac43e8-8599-11eb-9b86-f6efb0a4c207 last_name: Masson orcid: 0000-0002-2634-6283 - first_name: Tomas A full_name: Vega Zuniga, Tomas A id: 2E7C4E78-F248-11E8-B48F-1D18A9856A87 last_name: Vega Zuniga - first_name: Ximena full_name: Contreras, Ximena id: 475990FE-F248-11E8-B48F-1D18A9856A87 last_name: Contreras - first_name: Thomas full_name: Rülicke, Thomas last_name: Rülicke - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Maximilian A full_name: Jösch, Maximilian A id: 2BD278E6-F248-11E8-B48F-1D18A9856A87 last_name: Jösch orcid: 0000-0002-3937-1330 citation: ama: Burnett L, Koppensteiner P, Symonova O, et al. Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice. 2024. doi:10.15479/AT:ISTA:15385 apa: Burnett, L., Koppensteiner, P., Symonova, O., Masson, T., Vega Zuniga, T. A., Contreras, X., … Jösch, M. A. (2024). Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:15385 chicago: Burnett, Laura, Peter Koppensteiner, Olga Symonova, Tomas Masson, Tomas A Vega Zuniga, Ximena Contreras, Thomas Rülicke, Ryuichi Shigemoto, Gaia Novarino, and Maximilian A Jösch. “Shared Behavioural Impairments in Visual Perception and Place Avoidance across Different Autism Models Are Driven by Periaqueductal Grey Hypoexcitability in Setd5 Haploinsufficient Mice.” Institute of Science and Technology Austria, 2024. https://doi.org/10.15479/AT:ISTA:15385. ieee: L. Burnett et al., “Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice.” Institute of Science and Technology Austria, 2024. ista: Burnett L, Koppensteiner P, Symonova O, Masson T, Vega Zuniga TA, Contreras X, Rülicke T, Shigemoto R, Novarino G, Jösch MA. 2024. Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice, Institute of Science and Technology Austria, 10.15479/AT:ISTA:15385. mla: Burnett, Laura, et al. Shared Behavioural Impairments in Visual Perception and Place Avoidance across Different Autism Models Are Driven by Periaqueductal Grey Hypoexcitability in Setd5 Haploinsufficient Mice. Institute of Science and Technology Austria, 2024, doi:10.15479/AT:ISTA:15385. short: L. Burnett, P. Koppensteiner, O. Symonova, T. Masson, T.A. Vega Zuniga, X. Contreras, T. Rülicke, R. Shigemoto, G. Novarino, M.A. Jösch, (2024). corr_author: '1' date_created: 2024-05-13T15:04:04Z date_published: 2024-05-15T00:00:00Z date_updated: 2025-09-08T07:57:11Z day: '15' ddc: - '570' department: - _id: MaJö - _id: PreCl - _id: SiHi - _id: RySh - _id: GaNo doi: 10.15479/AT:ISTA:15385 file: - access_level: open_access checksum: 9205eb0876f0f08552dbad80d6884b4b content_type: application/zip creator: mjoesch date_created: 2024-05-15T06:09:17Z date_updated: 2024-05-15T06:09:17Z file_id: '15396' file_name: PatchClamp.zip file_size: '1149617663' relation: main_file success: 1 - access_level: open_access content_type: application/zip creator: mjoesch date_created: 2024-05-15T06:09:12Z date_updated: 2024-05-15T06:09:12Z file_id: '15397' file_name: SiliconProbe.zip file_size: '564903112' relation: main_file success: 1 - access_level: open_access checksum: 49a807bbab06b5fada38f532e2176e2e content_type: application/zip creator: mjoesch date_created: 2024-05-15T06:09:14Z date_updated: 2024-05-15T06:09:14Z file_id: '15398' file_name: WesternBlot.zip file_size: '11685703' relation: main_file success: 1 - access_level: open_access checksum: beeeeaa43770090f3b291209ed6b0623 content_type: application/zip creator: mjoesch date_created: 2024-05-15T06:09:38Z date_updated: 2024-05-15T06:09:38Z file_id: '15399' file_name: Behaviour.zip file_size: '1335626779' relation: main_file success: 1 - access_level: open_access checksum: 8862ad7719388304d1d19f8e7db8bb00 content_type: text/plain creator: mjoesch date_created: 2024-05-16T09:08:20Z date_updated: 2024-05-16T09:08:20Z file_id: '15400' file_name: Readme_Data.txt file_size: 18841 relation: main_file success: 1 file_date_updated: 2024-05-16T09:08:20Z has_accepted_license: '1' keyword: - ASD - periaqueductal gray - perception - behavior - potassium channels license: https://creativecommons.org/licenses/by-nc/4.0/ month: '05' oa: 1 oa_version: Published Version publisher: Institute of Science and Technology Austria related_material: record: - id: '17142' relation: used_in_publication status: public status: public title: Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice tmp: image: /images/cc_by_nc.png legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) short: CC BY-NC (4.0) type: research_data user_id: 68b8ca59-c5b3-11ee-8790-cd641c68093d year: '2024' ... --- APC_amount: 6081,83 EUR DOAJ_listed: '1' OA_place: publisher OA_type: gold _id: '17142' abstract: - lang: eng text: Despite the diverse genetic origins of autism spectrum disorders (ASDs), affected individuals share strikingly similar and correlated behavioural traits that include perceptual and sensory processing challenges. Notably, the severity of these sensory symptoms is often predictive of the expression of other autistic traits. However, the origin of these perceptual deficits remains largely elusive. Here, we show a recurrent impairment in visual threat perception that is similarly impaired in 3 independent mouse models of ASD with different molecular aetiologies. Interestingly, this deficit is associated with reduced avoidance of threatening environments—a nonperceptual trait. Focusing on a common cause of ASDs, the Setd5 gene mutation, we define the molecular mechanism. We show that the perceptual impairment is caused by a potassium channel (Kv1)-mediated hypoexcitability in a subcortical node essential for the initiation of escape responses, the dorsal periaqueductal grey (dPAG). Targeted pharmacological Kv1 blockade rescued both perceptual and place avoidance deficits, causally linking seemingly unrelated trait deficits to the dPAG. Furthermore, we show that different molecular mechanisms converge on similar behavioural phenotypes by demonstrating that the autism models Cul3 and Ptchd1, despite having similar behavioural phenotypes, differ in their functional and molecular alteration. Our findings reveal a link between rapid perception controlled by subcortical pathways and appropriate learned interactions with the environment and define a nondevelopmental source of such deficits in ASD. acknowledgement: 'This work was supported by a European Research Council Starting Grant 756502 (MJ). ' article_number: e3002668 article_processing_charge: Yes article_type: original author: - first_name: Laura full_name: Burnett, Laura id: 3B717F68-F248-11E8-B48F-1D18A9856A87 last_name: Burnett orcid: 0000-0002-8937-410X - first_name: Peter full_name: Koppensteiner, Peter id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87 last_name: Koppensteiner orcid: 0000-0002-3509-1948 - first_name: Olga full_name: Symonova, Olga id: 3C0C7BC6-F248-11E8-B48F-1D18A9856A87 last_name: Symonova orcid: 0000-0003-2012-9947 - first_name: Tomas full_name: Masson, Tomas id: 93ac43e8-8599-11eb-9b86-f6efb0a4c207 last_name: Masson orcid: 0000-0002-2634-6283 - first_name: Tomas A full_name: Vega Zuniga, Tomas A id: 2E7C4E78-F248-11E8-B48F-1D18A9856A87 last_name: Vega Zuniga - first_name: Ximena full_name: Contreras, Ximena id: 475990FE-F248-11E8-B48F-1D18A9856A87 last_name: Contreras - first_name: Thomas full_name: Rülicke, Thomas last_name: Rülicke - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Maximilian A full_name: Jösch, Maximilian A id: 2BD278E6-F248-11E8-B48F-1D18A9856A87 last_name: Jösch orcid: 0000-0002-3937-1330 citation: ama: Burnett L, Koppensteiner P, Symonova O, et al. Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice. PLoS Biology. 2024;22. doi:10.1371/journal.pbio.3002668 apa: Burnett, L., Koppensteiner, P., Symonova, O., Masson, T., Vega Zuniga, T. A., Contreras, X., … Jösch, M. A. (2024). Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice. PLoS Biology. Public Library of Science. https://doi.org/10.1371/journal.pbio.3002668 chicago: Burnett, Laura, Peter Koppensteiner, Olga Symonova, Tomas Masson, Tomas A Vega Zuniga, Ximena Contreras, Thomas Rülicke, Ryuichi Shigemoto, Gaia Novarino, and Maximilian A Jösch. “Shared Behavioural Impairments in Visual Perception and Place Avoidance across Different Autism Models Are Driven by Periaqueductal Grey Hypoexcitability in Setd5 Haploinsufficient Mice.” PLoS Biology. Public Library of Science, 2024. https://doi.org/10.1371/journal.pbio.3002668. ieee: L. Burnett et al., “Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice,” PLoS Biology, vol. 22. Public Library of Science, 2024. ista: Burnett L, Koppensteiner P, Symonova O, Masson T, Vega Zuniga TA, Contreras X, Rülicke T, Shigemoto R, Novarino G, Jösch MA. 2024. Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice. PLoS Biology. 22, e3002668. mla: Burnett, Laura, et al. “Shared Behavioural Impairments in Visual Perception and Place Avoidance across Different Autism Models Are Driven by Periaqueductal Grey Hypoexcitability in Setd5 Haploinsufficient Mice.” PLoS Biology, vol. 22, e3002668, Public Library of Science, 2024, doi:10.1371/journal.pbio.3002668. short: L. Burnett, P. Koppensteiner, O. Symonova, T. Masson, T.A. Vega Zuniga, X. Contreras, T. Rülicke, R. Shigemoto, G. Novarino, M.A. Jösch, PLoS Biology 22 (2024). corr_author: '1' date_created: 2024-06-16T22:01:05Z date_published: 2024-06-10T00:00:00Z date_updated: 2025-09-08T07:57:11Z day: '10' ddc: - '570' department: - _id: RySh - _id: GaNo - _id: MaJö doi: 10.1371/journal.pbio.3002668 ec_funded: 1 external_id: isi: - '001246176800003' pmid: - '38857283' file: - access_level: open_access checksum: 496e1aa4fd5b92b7e4087ecc2c964133 content_type: application/pdf creator: dernst date_created: 2025-01-09T10:39:41Z date_updated: 2025-01-09T10:39:41Z file_id: '18805' file_name: 2024_PloS_Burnett.pdf file_size: 4016568 relation: main_file success: 1 file_date_updated: 2025-01-09T10:39:41Z has_accepted_license: '1' intvolume: ' 22' isi: 1 language: - iso: eng month: '06' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 2634E9D2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '756502' name: Circuits of Visual Attention publication: PLoS Biology publication_identifier: eissn: - 1545-7885 issn: - 1544-9173 publication_status: published publisher: Public Library of Science quality_controlled: '1' related_material: link: - relation: software url: https://doi.org/10.5281/zenodo.11130587 record: - id: '15385' relation: research_data status: public scopus_import: '1' status: public title: Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient 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: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 22 year: '2024' ... --- DOAJ_listed: '1' OA_place: publisher OA_type: gold _id: '17280' abstract: - lang: eng text: Adherens junction–associated protein 1 (AJAP1) has been implicated in brain diseases; however, a pathogenic mechanism has not been identified. AJAP1 is widely expressed in neurons and binds to γ-aminobutyric acid type B receptors (GBRs), which inhibit neurotransmitter release at most synapses in the brain. Here, we show that AJAP1 is selectively expressed in dendrites and trans-synaptically recruits GBRs to presynaptic sites of neurons expressing AJAP1. We have identified several monoallelic AJAP1 variants in individuals with epilepsy and/or neurodevelopmental disorders. Specifically, we show that the variant p.(W183C) lacks binding to GBRs, resulting in the inability to recruit them. Ultrastructural analysis revealed significantly decreased presynaptic GBR levels in Ajap1−/− and Ajap1W183C/+ mice. Consequently, these mice exhibited reduced GBR-mediated presynaptic inhibition at excitatory and inhibitory synapses, along with impaired synaptic plasticity. Our study reveals that AJAP1 enables the postsynaptic neuron to regulate the level of presynaptic GBR-mediated inhibition, supporting the clinical relevance of loss-of-function AJAP1 variants. acknowledgement: "Ajap1HA/HA and Ajap1W183C/+ mice were generated in collaboration with Pawel Pelczar at the center for transgenic models at the University of Basel, Switzerland. We thank the imaging core facility (IMCF, University of Basel) and in particular A. Ferrand for the technical assistance provided on the OMX 3D-SIM microscope.\r\nThis work was supported by a grant from the Swiss National Science Foundation (SNF) to B.B. (31003A-152970, 310030B-201291), an NIH grant to E.A. and E.H.S. (R01NS058721), DFG grants to B.F. (TRR 152 project ID 239283807, FA 332/15-1, 16-1), and grants to P.S. from AIMS-2-TRIALS, which are supported by the Innovative Medicines Initiatives from the European Commission joint undertaking under grant agreement No 777394." article_number: adk5462 article_processing_charge: Yes article_type: original author: - first_name: Simon full_name: Früh, Simon last_name: Früh - first_name: Sami full_name: Boudkkazi, Sami last_name: Boudkkazi - first_name: Peter full_name: Koppensteiner, Peter id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87 last_name: Koppensteiner orcid: 0000-0002-3509-1948 - first_name: Vita full_name: Sereikaite, Vita last_name: Sereikaite - first_name: Li Yuan full_name: Chen, Li Yuan last_name: Chen - first_name: Diego full_name: Fernandez-Fernandez, Diego last_name: Fernandez-Fernandez - first_name: Pascal D. full_name: Rem, Pascal D. last_name: Rem - first_name: Daniel full_name: Ulrich, Daniel last_name: Ulrich - first_name: Jochen full_name: Schwenk, Jochen last_name: Schwenk - first_name: Ziyang full_name: Chen, Ziyang last_name: Chen - first_name: Elodie Le full_name: Monnier, Elodie Le last_name: Monnier - first_name: Thorsten full_name: Fritzius, Thorsten last_name: Fritzius - first_name: Sabrina M. full_name: Innocenti, Sabrina M. last_name: Innocenti - first_name: Valérie full_name: Besseyrias, Valérie last_name: Besseyrias - first_name: Luca full_name: Trovò, Luca last_name: Trovò - first_name: Michal full_name: Stawarski, Michal last_name: Stawarski - first_name: Emanuela full_name: Argilli, Emanuela last_name: Argilli - first_name: Elliott H. full_name: Sherr, Elliott H. last_name: Sherr - first_name: Bregje full_name: Van Bon, Bregje last_name: Van Bon - first_name: Erik Jan full_name: Kamsteeg, Erik Jan last_name: Kamsteeg - first_name: Maria full_name: Iascone, Maria last_name: Iascone - first_name: Alba full_name: Pilotta, Alba last_name: Pilotta - first_name: Maria R. full_name: Cutrì, Maria R. last_name: Cutrì - first_name: Mahshid S. full_name: Azamian, Mahshid S. last_name: Azamian - first_name: Andrés full_name: Hernández-García, Andrés last_name: Hernández-García - first_name: Seema R. full_name: Lalani, Seema R. last_name: Lalani - first_name: Jill A. full_name: Rosenfeld, Jill A. last_name: Rosenfeld - first_name: Xiaonan full_name: Zhao, Xiaonan last_name: Zhao - first_name: Tiphanie P. full_name: Vogel, Tiphanie P. last_name: Vogel - first_name: Herda full_name: Ona, Herda last_name: Ona - first_name: Daryl A. full_name: Scott, Daryl A. last_name: Scott - first_name: Peter full_name: Scheiffele, Peter last_name: Scheiffele - first_name: Kristian full_name: Strømgaard, Kristian last_name: Strømgaard - first_name: Mehdi full_name: Tafti, Mehdi last_name: Tafti - first_name: Martin full_name: Gassmann, Martin last_name: Gassmann - first_name: Bernd full_name: Fakler, Bernd last_name: Fakler - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Bernhard full_name: Bettler, Bernhard last_name: Bettler citation: ama: Früh S, Boudkkazi S, Koppensteiner P, et al. Monoallelic de novo AJAP1 loss-of- function variants disrupt trans-synaptic control of neurotransmitter release. Science Advances. 2024;10(28). doi:10.1126/sciadv.adk5462 apa: Früh, S., Boudkkazi, S., Koppensteiner, P., Sereikaite, V., Chen, L. Y., Fernandez-Fernandez, D., … Bettler, B. (2024). Monoallelic de novo AJAP1 loss-of- function variants disrupt trans-synaptic control of neurotransmitter release. Science Advances. American Association for the Advancement of Science. https://doi.org/10.1126/sciadv.adk5462 chicago: Früh, Simon, Sami Boudkkazi, Peter Koppensteiner, Vita Sereikaite, Li Yuan Chen, Diego Fernandez-Fernandez, Pascal D. Rem, et al. “Monoallelic de Novo AJAP1 Loss-of- Function Variants Disrupt Trans-Synaptic Control of Neurotransmitter Release.” Science Advances. American Association for the Advancement of Science, 2024. https://doi.org/10.1126/sciadv.adk5462. ieee: S. Früh et al., “Monoallelic de novo AJAP1 loss-of- function variants disrupt trans-synaptic control of neurotransmitter release,” Science Advances, vol. 10, no. 28. American Association for the Advancement of Science, 2024. ista: Früh S, Boudkkazi S, Koppensteiner P, Sereikaite V, Chen LY, Fernandez-Fernandez D, Rem PD, Ulrich D, Schwenk J, Chen Z, Monnier EL, Fritzius T, Innocenti SM, Besseyrias V, Trovò L, Stawarski M, Argilli E, Sherr EH, Van Bon B, Kamsteeg EJ, Iascone M, Pilotta A, Cutrì MR, Azamian MS, Hernández-García A, Lalani SR, Rosenfeld JA, Zhao X, Vogel TP, Ona H, Scott DA, Scheiffele P, Strømgaard K, Tafti M, Gassmann M, Fakler B, Shigemoto R, Bettler B. 2024. Monoallelic de novo AJAP1 loss-of- function variants disrupt trans-synaptic control of neurotransmitter release. Science Advances. 10(28), adk5462. mla: Früh, Simon, et al. “Monoallelic de Novo AJAP1 Loss-of- Function Variants Disrupt Trans-Synaptic Control of Neurotransmitter Release.” Science Advances, vol. 10, no. 28, adk5462, American Association for the Advancement of Science, 2024, doi:10.1126/sciadv.adk5462. short: S. Früh, S. Boudkkazi, P. Koppensteiner, V. Sereikaite, L.Y. Chen, D. Fernandez-Fernandez, P.D. Rem, D. Ulrich, J. Schwenk, Z. Chen, E.L. Monnier, T. Fritzius, S.M. Innocenti, V. Besseyrias, L. Trovò, M. Stawarski, E. Argilli, E.H. Sherr, B. Van Bon, E.J. Kamsteeg, M. Iascone, A. Pilotta, M.R. Cutrì, M.S. Azamian, A. Hernández-García, S.R. Lalani, J.A. Rosenfeld, X. Zhao, T.P. Vogel, H. Ona, D.A. Scott, P. Scheiffele, K. Strømgaard, M. Tafti, M. Gassmann, B. Fakler, R. Shigemoto, B. Bettler, Science Advances 10 (2024). date_created: 2024-07-21T22:01:01Z date_published: 2024-07-12T00:00:00Z date_updated: 2025-09-08T08:15:54Z day: '12' ddc: - '570' department: - _id: RySh - _id: PreCl doi: 10.1126/sciadv.adk5462 external_id: isi: - '001280159000022' pmid: - '38985877' file: - access_level: open_access checksum: 9cbc4501fcd4ba1c0811fd244031422b content_type: application/pdf creator: dernst date_created: 2024-07-22T06:29:27Z date_updated: 2024-07-22T06:29:27Z file_id: '17287' file_name: 2024_ScienceAdv_Früh.pdf file_size: 7241489 relation: main_file success: 1 file_date_updated: 2024-07-22T06:29:27Z has_accepted_license: '1' intvolume: ' 10' isi: 1 issue: '28' language: - iso: eng month: '07' oa: 1 oa_version: Published Version pmid: 1 publication: Science Advances publication_identifier: eissn: - 2375-2548 publication_status: published publisher: American Association for the Advancement of Science quality_controlled: '1' scopus_import: '1' status: public title: Monoallelic de novo AJAP1 loss-of- function variants disrupt trans-synaptic control of neurotransmitter release 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: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 10 year: '2024' ... --- DOAJ_listed: '1' OA_place: publisher OA_type: gold _id: '17457' abstract: - lang: eng text: "Autoantibodies against the protein leucine-rich glioma inactivated 1 (LGI1) cause the most\r\ncommon subtype of autoimmune encephalitis with predominant involvement of the limbic\r\nsystem, associated with seizures and memory deficits. LGI1 and its receptor ADAM22 are part\r\nof a transsynaptic protein complex that includes several proteins involved in presynaptic\r\nneurotransmitter release and postsynaptic glutamate sensing. Autoantibodies against LGI1\r\nincrease excitatory synaptic strength, but studies that genetically disrupt the LGI1-ADAM22\r\ncomplex report a reduction in postsynaptic glutamate receptor-mediated responses. Thus, the\r\nmechanisms underlying the increased synaptic strength induced by LGI1 autoantibodies remain elusive, and the contributions of presynaptic molecules to the LGI1-transsynaptic complex remain unclear. We therefore investigated the presynaptic mechanisms that mediate\r\nautoantibody-induced synaptic strengthening." acknowledged_ssus: - _id: Bio - _id: EM-Fac acknowledgement: 'The authors thank Claudia Sommer for expert technical assistance, the Electron Microscopy Facility of IST-Austria for resources, and Tereza Belinova in the Imaging and Optics Facility of IST-Austria for 3D reconstruction. ' article_processing_charge: Yes article_type: original author: - first_name: Andreas full_name: Ritzau-Jost, Andreas last_name: Ritzau-Jost - first_name: Felix full_name: Gsell, Felix last_name: Gsell - first_name: Josefine full_name: Sell, Josefine last_name: Sell - first_name: Stefan full_name: Sachs, Stefan last_name: Sachs - first_name: Jacqueline-Claire full_name: Montanaro-Punzengruber, Jacqueline-Claire id: 3786AB44-F248-11E8-B48F-1D18A9856A87 last_name: Montanaro-Punzengruber - first_name: Toni full_name: Kirmann, Toni last_name: Kirmann - first_name: Sebastian full_name: Maaß, Sebastian last_name: Maaß - first_name: Sarosh R. full_name: Irani, Sarosh R. last_name: Irani - first_name: Christian full_name: Werner, Christian last_name: Werner - first_name: Christian full_name: Geis, Christian last_name: Geis - first_name: Markus full_name: Sauer, Markus last_name: Sauer - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Stefan full_name: Hallermann, Stefan last_name: Hallermann citation: ama: Ritzau-Jost A, Gsell F, Sell J, et al. LGI1 autoantibodies enhance synaptic transmission by presynaptic Kv1 loss and increased action potential broadening. Neurology, Neuroimmunology and Neuroinflammation. 2024;11(5):e200284. doi:10.1212/NXI.0000000000200284 apa: Ritzau-Jost, A., Gsell, F., Sell, J., Sachs, S., Montanaro-Punzengruber, J.-C., Kirmann, T., … Hallermann, S. (2024). LGI1 autoantibodies enhance synaptic transmission by presynaptic Kv1 loss and increased action potential broadening. Neurology, Neuroimmunology and Neuroinflammation. Wolters Kluwer. https://doi.org/10.1212/NXI.0000000000200284 chicago: Ritzau-Jost, Andreas, Felix Gsell, Josefine Sell, Stefan Sachs, Jacqueline-Claire Montanaro-Punzengruber, Toni Kirmann, Sebastian Maaß, et al. “LGI1 Autoantibodies Enhance Synaptic Transmission by Presynaptic Kv1 Loss and Increased Action Potential Broadening.” Neurology, Neuroimmunology and Neuroinflammation. Wolters Kluwer, 2024. https://doi.org/10.1212/NXI.0000000000200284. ieee: A. Ritzau-Jost et al., “LGI1 autoantibodies enhance synaptic transmission by presynaptic Kv1 loss and increased action potential broadening,” Neurology, Neuroimmunology and Neuroinflammation, vol. 11, no. 5. Wolters Kluwer, p. e200284, 2024. ista: Ritzau-Jost A, Gsell F, Sell J, Sachs S, Montanaro-Punzengruber J-C, Kirmann T, Maaß S, Irani SR, Werner C, Geis C, Sauer M, Shigemoto R, Hallermann S. 2024. LGI1 autoantibodies enhance synaptic transmission by presynaptic Kv1 loss and increased action potential broadening. Neurology, Neuroimmunology and Neuroinflammation. 11(5), e200284. mla: Ritzau-Jost, Andreas, et al. “LGI1 Autoantibodies Enhance Synaptic Transmission by Presynaptic Kv1 Loss and Increased Action Potential Broadening.” Neurology, Neuroimmunology and Neuroinflammation, vol. 11, no. 5, Wolters Kluwer, 2024, p. e200284, doi:10.1212/NXI.0000000000200284. short: A. Ritzau-Jost, F. Gsell, J. Sell, S. Sachs, J.-C. Montanaro-Punzengruber, T. Kirmann, S. Maaß, S.R. Irani, C. Werner, C. Geis, M. Sauer, R. Shigemoto, S. Hallermann, Neurology, Neuroimmunology and Neuroinflammation 11 (2024) e200284. date_created: 2024-08-25T22:01:07Z date_published: 2024-09-01T00:00:00Z date_updated: 2025-09-08T08:59:37Z day: '01' ddc: - '570' department: - _id: RySh doi: 10.1212/NXI.0000000000200284 external_id: isi: - '001291908600001' pmid: - '39141878' file: - access_level: open_access checksum: 1e6d1230e0387f72752e3268f5330c9e content_type: application/pdf creator: dernst date_created: 2025-01-09T13:42:42Z date_updated: 2025-01-09T13:42:42Z file_id: '18815' file_name: 2024_NeurologyNeuroimmNeuroinflamm_RitzauJost.pdf file_size: 855818 relation: main_file success: 1 file_date_updated: 2025-01-09T13:42:42Z has_accepted_license: '1' intvolume: ' 11' isi: 1 issue: '5' language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: e200284 pmid: 1 project: - _id: 05970B30-7A3F-11EA-A408-12923DDC885E grant_number: I04638 name: LGI1 antibody-induced pathophysiology in synapses publication: Neurology, Neuroimmunology and Neuroinflammation publication_identifier: eissn: - 2332-7812 publication_status: published publisher: Wolters Kluwer quality_controlled: '1' related_material: link: - relation: earlier_version url: https://doi.org/10.1101/2023.10.04.560631 scopus_import: '1' status: public title: LGI1 autoantibodies enhance synaptic transmission by presynaptic Kv1 loss and increased action potential broadening 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: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 11 year: '2024' ... --- _id: '12875' abstract: - lang: eng text: The superior colliculus (SC) in the mammalian midbrain is essential for multisensory integration and is composed of a rich diversity of excitatory and inhibitory neurons and glia. However, the developmental principles directing the generation of SC cell-type diversity are not understood. Here, we pursued systematic cell lineage tracing in silico and in vivo, preserving full spatial information, using genetic mosaic analysis with double markers (MADM)-based clonal analysis with single-cell sequencing (MADM-CloneSeq). The analysis of clonally related cell lineages revealed that radial glial progenitors (RGPs) in SC are exceptionally multipotent. Individual resident RGPs have the capacity to produce all excitatory and inhibitory SC neuron types, even at the stage of terminal division. While individual clonal units show no pre-defined cellular composition, the establishment of appropriate relative proportions of distinct neuronal types occurs in a PTEN-dependent manner. Collectively, our findings provide an inaugural framework at the single-RGP/-cell level of the mammalian SC ontogeny. acknowledged_ssus: - _id: Bio - _id: M-Shop - _id: LifeSc - _id: PreCl acknowledgement: "We thank Liqun Luo for his continued support, for providing essential resources for generating Fzd10-CreER mice which were generated in his laboratory, and for comments on the manuscript; W. Zhong for providing Nestin-Cre transgenic mouse line for this study; A. Heger for mouse colony management; R. Beattie and T. Asenov for designing and producing components of acute slice recovery chamber for MADM-CloneSeq experiments; and K. Leopold, J. Rodarte and N. Amberg for initial experiments, technical support and/or assistance. This study was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Imaging & Optics Facility (IOF), Laboratory Support Facility (LSF), Miba Machine Shop, and Pre-clinical Facility (PCF). G.C. received funding from European Commission (IST plus postdoctoral fellowship). This work was supported by ISTA institutional\r\nfunds; the Austrian Science Fund Special Research Programmes (FWF SFB F78 Neuro Stem Modulation) to S.H. " article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Giselle T full_name: Cheung, Giselle T id: 471195F6-F248-11E8-B48F-1D18A9856A87 last_name: Cheung orcid: 0000-0001-8457-2572 - first_name: Florian full_name: Pauler, Florian id: 48EA0138-F248-11E8-B48F-1D18A9856A87 last_name: Pauler orcid: 0000-0002-7462-0048 - first_name: Peter full_name: Koppensteiner, Peter id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87 last_name: Koppensteiner orcid: 0000-0002-3509-1948 - first_name: Thomas full_name: Krausgruber, Thomas last_name: Krausgruber - first_name: Carmen full_name: Streicher, Carmen id: 36BCB99C-F248-11E8-B48F-1D18A9856A87 last_name: Streicher - first_name: Martin full_name: Schrammel, Martin id: f13e7cae-e8bd-11ed-841a-96dedf69f46d last_name: Schrammel - first_name: Natalie Y full_name: Özgen, Natalie Y id: e68ece33-f6e0-11ea-865d-ae1031dcc090 last_name: Özgen - first_name: Alexis full_name: Ivec, Alexis id: 1d144691-e8be-11ed-9b33-bdd3077fad4c last_name: Ivec - first_name: Christoph full_name: Bock, Christoph last_name: Bock - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 citation: ama: Cheung GT, Pauler F, Koppensteiner P, et al. Multipotent progenitors instruct ontogeny of the superior colliculus. Neuron. 2024;112(2):230-246.e11. doi:10.1016/j.neuron.2023.11.009 apa: Cheung, G. T., Pauler, F., Koppensteiner, P., Krausgruber, T., Streicher, C., Schrammel, M., … Hippenmeyer, S. (2024). Multipotent progenitors instruct ontogeny of the superior colliculus. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2023.11.009 chicago: Cheung, Giselle T, Florian Pauler, Peter Koppensteiner, Thomas Krausgruber, Carmen Streicher, Martin Schrammel, Natalie Y Özgen, et al. “Multipotent Progenitors Instruct Ontogeny of the Superior Colliculus.” Neuron. Elsevier, 2024. https://doi.org/10.1016/j.neuron.2023.11.009. ieee: G. T. Cheung et al., “Multipotent progenitors instruct ontogeny of the superior colliculus,” Neuron, vol. 112, no. 2. Elsevier, p. 230–246.e11, 2024. ista: Cheung GT, Pauler F, Koppensteiner P, Krausgruber T, Streicher C, Schrammel M, Özgen NY, Ivec A, Bock C, Shigemoto R, Hippenmeyer S. 2024. Multipotent progenitors instruct ontogeny of the superior colliculus. Neuron. 112(2), 230–246.e11. mla: Cheung, Giselle T., et al. “Multipotent Progenitors Instruct Ontogeny of the Superior Colliculus.” Neuron, vol. 112, no. 2, Elsevier, 2024, p. 230–246.e11, doi:10.1016/j.neuron.2023.11.009. short: G.T. Cheung, F. Pauler, P. Koppensteiner, T. Krausgruber, C. Streicher, M. Schrammel, N.Y. Özgen, A. Ivec, C. Bock, R. Shigemoto, S. Hippenmeyer, Neuron 112 (2024) 230–246.e11. corr_author: '1' date_created: 2023-04-27T09:41:48Z date_published: 2024-01-17T00:00:00Z date_updated: 2025-12-30T10:54:12Z day: '17' ddc: - '570' department: - _id: SiHi - _id: RySh doi: 10.1016/j.neuron.2023.11.009 external_id: isi: - '001163937900001' pmid: - '38096816' file: - access_level: open_access checksum: 32b3788f7085cf44a84108d8faaff3ce content_type: application/pdf creator: dernst date_created: 2024-02-06T13:56:15Z date_updated: 2024-02-06T13:56:15Z file_id: '14944' file_name: 2024_Neuron_Cheung.pdf file_size: 5942467 relation: main_file success: 1 file_date_updated: 2024-02-06T13:56:15Z has_accepted_license: '1' intvolume: ' 112' isi: 1 issue: '2' language: - iso: eng month: '01' oa: 1 oa_version: Published Version page: 230-246.e11 pmid: 1 project: - _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E grant_number: F7805 name: Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression publication: Neuron publication_identifier: issn: - 0896-6273 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: link: - description: News on ISTA Website relation: press_release url: https://ista.ac.at/en/news/the-pedigree-of-brain-cells/ scopus_import: '1' status: public title: Multipotent progenitors instruct ontogeny of the superior colliculus 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: 112 year: '2024' ... --- APC_amount: 6248,82 EUR DOAJ_listed: '1' OA_place: publisher OA_type: gold _id: '18603' abstract: - lang: eng text: It is widely believed that information storage in neuronal circuits involves nanoscopic structural changes at synapses, resulting in the formation of synaptic engrams. However, direct evidence for this hypothesis is lacking. To test this conjecture, we combined chemical potentiation, functional analysis by paired pre-postsynaptic recordings, and structural analysis by electron microscopy (EM) and freeze-fracture replica labeling (FRL) at the rodent hippocampal mossy fiber synapse, a key synapse in the trisynaptic circuit of the hippocampus. Biophysical analysis of synaptic transmission revealed that forskolin-induced chemical potentiation increased the readily releasable vesicle pool size and vesicular release probability by 146% and 49%, respectively. Structural analysis of mossy fiber synapses by EM and FRL demonstrated an increase in the number of vesicles close to the plasma membrane and the number of clusters of the priming protein Munc13-1, indicating an increase in the number of both docked and primed vesicles. Furthermore, FRL analysis revealed a significant reduction of the distance between Munc13-1 and CaV2.1 Ca2+ channels, suggesting reconfiguration of the channel-vesicle coupling nanotopography. Our results indicate that presynaptic plasticity is associated with structural reorganization of active zones. We propose that changes in potential nanoscopic organization at synaptic vesicle release sites may be correlates of learning and memory at a plastic central synapse. acknowledged_ssus: - _id: EM-Fac - _id: PreCl acknowledgement: "We thank Carolina Borges-Merjane, Jing-Jing Chen, Katharina Lichter, and Samuel Young for critically reading the manuscript; the Electron Microscopy Facility of ISTA, in particular Vanessa Zheden, for extensive support, advice, and experimental assistance; the Preclinical Facility of ISTA, in particular Victoria Wimmer and Michael Schunn, for experimental assistance; Florian Marr and Christina Altmutter for technical support; Alois Schlögl for help with analysis; and Eleftheria Kralli-Beller for manuscript editing. We also thank Cordelia Imig for providing Munc13-1cKO-Munc13-2/3(−/−) mutant mice. Part of the work has been published in O.K.’s thesis in partial fulfillment of the requirements for the degree of Doctor of Philosophy.\r\nThis project received funding from the European Research Council and European Union’s Horizon 2020 research and innovation programme (ERC 692692 to P.J.; https://cordis.europa.eu/project/id/692692/de) and from the Fond zur Förderung der Wissenschaftlichen Forschung (Z312-B27 Wittgenstein award to P.J., https://www.fwf.ac.at/en/funding/portfolio/projects/fwf-wittgenstein-award; W1205-B09 and P36232-B to P.J., https://www.fwf.ac.at/en/funding; I6166-B to R.S.; https://www.fwf.ac.at/en/funding). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." article_number: e3002879 article_processing_charge: Yes article_type: original author: - first_name: Olena full_name: Kim, Olena id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87 last_name: Kim orcid: 0000-0003-2344-1039 - first_name: Yuji full_name: Okamoto, Yuji id: 3337E116-F248-11E8-B48F-1D18A9856A87 last_name: Okamoto orcid: 0000-0003-0408-6094 - first_name: Walter full_name: Kaufmann, Walter id: 3F99E422-F248-11E8-B48F-1D18A9856A87 last_name: Kaufmann orcid: 0000-0001-9735-5315 - first_name: Nils full_name: Brose, Nils last_name: Brose - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: Kim O, Okamoto Y, Kaufmann W, Brose N, Shigemoto R, Jonas PM. Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. PLoS Biology. 2024;22(11). doi:10.1371/journal.pbio.3002879 apa: Kim, O., Okamoto, Y., Kaufmann, W., Brose, N., Shigemoto, R., & Jonas, P. M. (2024). Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. PLoS Biology. Public Library of Science. https://doi.org/10.1371/journal.pbio.3002879 chicago: Kim, Olena, Yuji Okamoto, Walter Kaufmann, Nils Brose, Ryuichi Shigemoto, and Peter M Jonas. “Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber Boutons.” PLoS Biology. Public Library of Science, 2024. https://doi.org/10.1371/journal.pbio.3002879. ieee: O. Kim, Y. Okamoto, W. Kaufmann, N. Brose, R. Shigemoto, and P. M. Jonas, “Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons,” PLoS Biology, vol. 22, no. 11. Public Library of Science, 2024. ista: Kim O, Okamoto Y, Kaufmann W, Brose N, Shigemoto R, Jonas PM. 2024. Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. PLoS Biology. 22(11), e3002879. mla: Kim, Olena, et al. “Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber Boutons.” PLoS Biology, vol. 22, no. 11, e3002879, Public Library of Science, 2024, doi:10.1371/journal.pbio.3002879. short: O. Kim, Y. Okamoto, W. Kaufmann, N. Brose, R. Shigemoto, P.M. Jonas, PLoS Biology 22 (2024). corr_author: '1' date_created: 2024-12-01T23:01:54Z date_published: 2024-11-18T00:00:00Z date_updated: 2026-04-16T12:20:34Z day: '18' ddc: - '570' department: - _id: PeJo - _id: EM-Fac - _id: RySh doi: 10.1371/journal.pbio.3002879 ec_funded: 1 external_id: isi: - '001358568700003' pmid: - '39556620' file: - access_level: open_access checksum: 7de2dcb50deb65dde05c80082bb85a82 content_type: application/pdf creator: dernst date_created: 2024-12-03T08:56:53Z date_updated: 2024-12-03T08:56:53Z file_id: '18608' file_name: 2024_PloSBio_Kim.pdf file_size: 3057631 relation: main_file success: 1 file_date_updated: 2024-12-03T08:56:53Z has_accepted_license: '1' intvolume: ' 22' isi: 1 issue: '11' language: - iso: eng month: '11' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glutamatergic synapse - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: Synaptic communication in neuronal microcircuits - _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5 grant_number: P36232 name: Mechanisms of GABA release in hippocampal circuits - _id: b1b85715-d554-11ed-a5ad-84a07fc9f18e grant_number: I06166 name: Structural & functional basis of presynaptic plasticity - _id: 25C3DBB6-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W01205 name: Zellkommunikation in Gesundheit und Krankheit - _id: 3AC91DDA-15DF-11EA-824D-93A3E7B544D1 call_identifier: FWF name: FWF Open Access Fund publication: PLoS Biology publication_identifier: eissn: - 1545-7885 issn: - 1544-9173 publication_status: published publisher: Public Library of Science quality_controlled: '1' related_material: record: - id: '18296' relation: research_data status: public scopus_import: '1' status: public title: Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons 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: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 22 year: '2024' ... --- APC_amount: 5887,8 EUR OA_place: publisher OA_type: hybrid _id: '15084' abstract: - lang: eng text: "GABAB receptor (GBR) activation inhibits neurotransmitter release in axon terminals in the brain, except in medial habenula (MHb) terminals, which show robust potentiation. However, mechanisms underlying this enigmatic potentiation remain elusive. Here, we report that GBR activation on MHb terminals induces an activity-dependent transition from a facilitating, tonic to a depressing, phasic neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked synaptic vesicles (SVs) at the presynaptic active zone (AZ). Strikingly, the depressing phasic release exhibits looser coupling distance than the tonic release. Furthermore, the tonic and phasic release are selectively affected by deletion of synaptoporin (SPO) and Ca\r\n 2+\r\n -dependent activator protein for secretion 2 (CAPS2), respectively. SPO modulates augmentation, the short-term plasticity associated with tonic release, and CAPS2 retains the increased RRP for initial responses in phasic response trains. The cytosolic protein CAPS2 showed a SV-associated distribution similar to the vesicular transmembrane protein SPO, and they were colocalized in the same terminals. We developed the “Flash and Freeze-fracture” method, and revealed the release of SPO-associated vesicles in both tonic and phasic modes and activity-dependent recruitment of CAPS2 to the AZ during phasic release, which lasted several minutes. Overall, these results indicate that GBR activation translocates CAPS2 to the AZ along with the fusion of CAPS2-associated SVs, contributing to persistency of the RRP increase. Thus, we identified structural and molecular mechanisms underlying tonic and phasic neurotransmitter release and their transition by GBR activation in MHb terminals." acknowledged_ssus: - _id: M-Shop - _id: PreCl - _id: EM-Fac acknowledgement: We thank Erwin Neher and Ipe Ninan for critical comments on the manuscript. This project has received funding from the European Research Council (ERC) and European Commission, under the European Union’s Horizon 2020 research and innovation program (ERC grant agreement no. 694539 to R.S. and the Marie Skłodowska-Curie grant agreement no. 665385 to C.Ö.). This study was supported by the Cooperative Study Program of Center for Animal Resources and Collaborative Study of NINS. We thank Kohgaku Eguchi for statistical analysis, Yu Kasugai for additional EM imaging, Robert Beattie for the design of the slice recovery chamber for Flash and Freeze experiments, Todor Asenov from the ISTA machine shop for custom part preparations for high-pressure freezing, the ISTA preclinical facility for animal caretaking, and the ISTA EM facilities for technical support. article_number: e2301449121 article_processing_charge: Yes (in subscription journal) article_type: original author: - first_name: Peter full_name: Koppensteiner, Peter id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87 last_name: Koppensteiner orcid: 0000-0002-3509-1948 - first_name: Pradeep full_name: Bhandari, Pradeep id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87 last_name: Bhandari orcid: 0000-0003-0863-4481 - first_name: Hüseyin C full_name: Önal, Hüseyin C id: 4659D740-F248-11E8-B48F-1D18A9856A87 last_name: Önal orcid: 0000-0002-2771-2011 - first_name: Carolina full_name: Borges Merjane, Carolina id: 4305C450-F248-11E8-B48F-1D18A9856A87 last_name: Borges Merjane orcid: 0000-0003-0005-401X - first_name: Elodie full_name: Le Monnier, Elodie id: 3B59276A-F248-11E8-B48F-1D18A9856A87 last_name: Le Monnier - first_name: Utsa full_name: Roy, Utsa id: 4d26cf11-5355-11ee-ae5a-eb05e255b9b2 last_name: Roy - first_name: Yukihiro full_name: Nakamura, Yukihiro last_name: Nakamura - first_name: Tetsushi full_name: Sadakata, Tetsushi last_name: Sadakata - first_name: Makoto full_name: Sanbo, Makoto last_name: Sanbo - first_name: Masumi full_name: Hirabayashi, Masumi last_name: Hirabayashi - first_name: JeongSeop full_name: Rhee, JeongSeop last_name: Rhee - first_name: Nils full_name: Brose, Nils last_name: Brose - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: ama: Koppensteiner P, Bhandari P, Önal C, et al. GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. Proceedings of the National Academy of Sciences of the United States of America. 2024;121(8). doi:10.1073/pnas.2301449121 apa: Koppensteiner, P., Bhandari, P., Önal, C., Borges Merjane, C., Le Monnier, E., Roy, U., … Shigemoto, R. (2024). GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences. https://doi.org/10.1073/pnas.2301449121 chicago: Koppensteiner, Peter, Pradeep Bhandari, Cihan Önal, Carolina Borges Merjane, Elodie Le Monnier, Utsa Roy, Yukihiro Nakamura, et al. “GABAB Receptors Induce Phasic Release from Medial Habenula Terminals through Activity-Dependent Recruitment of Release-Ready Vesicles.” Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 2024. https://doi.org/10.1073/pnas.2301449121. ieee: P. Koppensteiner et al., “GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles,” Proceedings of the National Academy of Sciences of the United States of America, vol. 121, no. 8. National Academy of Sciences, 2024. ista: Koppensteiner P, Bhandari P, Önal C, Borges Merjane C, Le Monnier E, Roy U, Nakamura Y, Sadakata T, Sanbo M, Hirabayashi M, Rhee J, Brose N, Jonas PM, Shigemoto R. 2024. GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles. Proceedings of the National Academy of Sciences of the United States of America. 121(8), e2301449121. mla: Koppensteiner, Peter, et al. “GABAB Receptors Induce Phasic Release from Medial Habenula Terminals through Activity-Dependent Recruitment of Release-Ready Vesicles.” Proceedings of the National Academy of Sciences of the United States of America, vol. 121, no. 8, e2301449121, National Academy of Sciences, 2024, doi:10.1073/pnas.2301449121. short: P. Koppensteiner, P. Bhandari, C. Önal, C. Borges Merjane, E. Le Monnier, U. Roy, Y. Nakamura, T. Sadakata, M. Sanbo, M. Hirabayashi, J. Rhee, N. Brose, P.M. Jonas, R. Shigemoto, Proceedings of the National Academy of Sciences of the United States of America 121 (2024). corr_author: '1' date_created: 2024-03-05T09:23:55Z date_published: 2024-02-20T00:00:00Z date_updated: 2026-04-29T22:30:22Z day: '20' ddc: - '570' department: - _id: RySh - _id: PeJo doi: 10.1073/pnas.2301449121 ec_funded: 1 external_id: isi: - '001208567300006' pmid: - '38346189' file: - access_level: open_access checksum: b25b2a057c266ff317a48b0d54d6fc8a content_type: application/pdf creator: dernst date_created: 2024-03-12T13:42:42Z date_updated: 2024-03-12T13:42:42Z file_id: '15110' file_name: 2024_PNAS_Koppensteiner.pdf file_size: 13648221 relation: main_file success: 1 file_date_updated: 2024-03-12T13:42:42Z has_accepted_license: '1' intvolume: ' 121' isi: 1 issue: '8' language: - iso: eng month: '02' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 25CA28EA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '694539' name: 'In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour' - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication: Proceedings of the National Academy of Sciences of the United States of America publication_identifier: eissn: - 1091-6490 issn: - 0027-8424 publication_status: published publisher: National Academy of Sciences quality_controlled: '1' related_material: link: - description: News on ISTA Website relation: press_release url: https://ista.ac.at/en/news/neuronal-insights-flash-and-freeze-fracture/ record: - id: '13173' relation: research_data status: public - id: '19271' relation: dissertation_contains status: public scopus_import: '1' status: public title: GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 121 year: '2024' ... --- OA_place: publisher OA_type: hybrid PlanS_conform: '1' _id: '14843' abstract: - lang: eng text: The coupling between Ca2+ channels and release sensors is a key factor defining the signaling properties of a synapse. However, the coupling nanotopography at many synapses remains unknown, and it is unclear how it changes during development. To address these questions, we examined coupling at the cerebellar inhibitory basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission by paired recording and intracellular pipette perfusion revealed that the effects of exogenous Ca2+ chelators decreased during development, despite constant reliance of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked vesicles were only clustered at later developmental stages. Modeling suggested a developmental transformation from a more random to a more clustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission. acknowledged_ssus: - _id: EM-Fac - _id: PreCl - _id: M-Shop acknowledgement: We thank Drs. David DiGregorio and Erwin Neher for critically reading an earlier version of the manuscript, Ralf Schneggenburger for helpful discussions, Benjamin Suter and Katharina Lichter for support with image analysis, Chris Wojtan for advice on numerical solution of partial differential equations, Maria Reva for help with Ripley analysis, Alois Schlögl for programming, and Akari Hagiwara and Toshihisa Ohtsuka for anti-ELKS antibody. We are grateful to Florian Marr, Christina Altmutter, and Vanessa Zheden for excellent technical assistance and to Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA (Electron Microscopy Facility, Preclinical Facility, and Machine Shop). The project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 692692), the Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award; P 36232-B), all to P.J., and a DOC fellowship of the Austrian Academy of Sciences to J.-J.C. article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: JingJing full_name: Chen, JingJing id: 2C4E65C8-F248-11E8-B48F-1D18A9856A87 last_name: Chen - first_name: Walter full_name: Kaufmann, Walter id: 3F99E422-F248-11E8-B48F-1D18A9856A87 last_name: Kaufmann orcid: 0000-0001-9735-5315 - first_name: Chong full_name: Chen, Chong id: 3DFD581A-F248-11E8-B48F-1D18A9856A87 last_name: Chen - first_name: Itaru full_name: Arai, Itaru id: 32A73F6C-F248-11E8-B48F-1D18A9856A87 last_name: Arai - first_name: Olena full_name: Kim, Olena id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87 last_name: Kim orcid: 0000-0003-2344-1039 - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 citation: ama: Chen J, Kaufmann W, Chen C, et al. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron. 2024;112(5):755-771.e9. doi:10.1016/j.neuron.2023.12.002 apa: Chen, J., Kaufmann, W., Chen, C., Arai, itaru, Kim, O., Shigemoto, R., & Jonas, P. M. (2024). Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2023.12.002 chicago: Chen, JingJing, Walter Kaufmann, Chong Chen, itaru Arai, Olena Kim, Ryuichi Shigemoto, and Peter M Jonas. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” Neuron. Elsevier, 2024. https://doi.org/10.1016/j.neuron.2023.12.002. ieee: J. Chen et al., “Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse,” Neuron, vol. 112, no. 5. Elsevier, p. 755–771.e9, 2024. ista: Chen J, Kaufmann W, Chen C, Arai itaru, Kim O, Shigemoto R, Jonas PM. 2024. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron. 112(5), 755–771.e9. mla: Chen, JingJing, et al. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” Neuron, vol. 112, no. 5, Elsevier, 2024, p. 755–771.e9, doi:10.1016/j.neuron.2023.12.002. short: J. Chen, W. Kaufmann, C. Chen, itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas, Neuron 112 (2024) 755–771.e9. corr_author: '1' date_created: 2024-01-21T23:00:56Z date_published: 2024-03-06T00:00:00Z date_updated: 2026-04-29T22:30:24Z day: '06' ddc: - '570' department: - _id: PeJo - _id: EM-Fac - _id: RySh doi: 10.1016/j.neuron.2023.12.002 ec_funded: 1 external_id: isi: - '001202925700001' pmid: - '38215739' file: - access_level: open_access checksum: 30098b4f0209556ddfb3540a23d07ca5 content_type: application/pdf creator: dernst date_created: 2025-04-23T14:02:08Z date_updated: 2025-04-23T14:02:08Z file_id: '19614' file_name: 2024_Neuron_Chen.pdf file_size: 8192355 relation: main_file success: 1 file_date_updated: 2025-04-23T14:02:08Z has_accepted_license: '1' intvolume: ' 112' isi: 1 issue: '5' language: - iso: eng month: '03' oa: 1 oa_version: Published Version page: 755-771.e9 pmid: 1 project: - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glutamatergic synapse - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: Synaptic communication in neuronal microcircuits - _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5 grant_number: P36232 name: Mechanisms of GABA release in hippocampal circuits - _id: 26B66A3E-B435-11E9-9278-68D0E5697425 grant_number: '25383' name: Development of nanodomain coupling between Ca2+ channels and release sensors at a central inhibitory synapse publication: Neuron publication_identifier: eissn: - 1097-4199 issn: - 0896-6273 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: link: - description: News on ISTA Website relation: press_release url: https://ista.ac.at/en/news/synapses-brought-to-the-point/ record: - id: '15101' relation: dissertation_contains status: public scopus_import: '1' status: public title: Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse 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: 112 year: '2024' ... --- _id: '14253' abstract: - lang: eng text: Junctions between the endoplasmic reticulum (ER) and the plasma membrane (PM) are specialized membrane contacts ubiquitous in eukaryotic cells. Concentration of intracellular signaling machinery near ER-PM junctions allows these domains to serve critical roles in lipid and Ca2+ signaling and homeostasis. Subcellular compartmentalization of protein kinase A (PKA) signaling also regulates essential cellular functions, however, no specific association between PKA and ER-PM junctional domains is known. Here, we show that in brain neurons type I PKA is directed to Kv2.1 channel-dependent ER-PM junctional domains via SPHKAP, a type I PKA-specific anchoring protein. SPHKAP association with type I PKA regulatory subunit RI and ER-resident VAP proteins results in the concentration of type I PKA between stacked ER cisternae associated with ER-PM junctions. This ER-associated PKA signalosome enables reciprocal regulation between PKA and Ca2+ signaling machinery to support Ca2+ influx and excitation-transcription coupling. These data reveal that neuronal ER-PM junctions support a receptor-independent form of PKA signaling driven by membrane depolarization and intracellular Ca2+, allowing conversion of information encoded in electrical signals into biochemical changes universally recognized throughout the cell. acknowledgement: We thank Kayla Templeton and Peter Turcanu for technical assistance, Michelle Salemi for assistance with LC-MS data acquisition and analysis, Dr. Belvin Gong for advice on monoclonal antibody generation, Drs. Maria Casas Prat and Eamonn Dickson for assistance with super-resolution TIRF microscopy, Dr. Oscar Cerda for assistance with the design of TAT-FFAT peptides, Dr. Fernando Santana for helpful discussions, and Dr. Jodi Nunnari for a careful reading of our manuscript. We also thank Dr. Alan Howe, Dr. Sohum Mehta, and Dr. Jin Zhang for providing plasmids used in this study. This project was funded by NIH Grants R01NS114210 and R21NS101648 (J.S.T.), and F32NS108519 (N.C.V.). article_number: '5231' article_processing_charge: Yes article_type: original author: - first_name: Nicholas C. full_name: Vierra, Nicholas C. last_name: Vierra - first_name: Luisa full_name: Ribeiro-Silva, Luisa last_name: Ribeiro-Silva - first_name: Michael full_name: Kirmiz, Michael last_name: Kirmiz - first_name: Deborah full_name: Van Der List, Deborah last_name: Van Der List - first_name: Pradeep full_name: Bhandari, Pradeep id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87 last_name: Bhandari orcid: 0000-0003-0863-4481 - first_name: Olivia A. full_name: Mack, Olivia A. last_name: Mack - first_name: James full_name: Carroll, James last_name: Carroll - first_name: Elodie full_name: Le Monnier, Elodie id: 3B59276A-F248-11E8-B48F-1D18A9856A87 last_name: Le Monnier - first_name: Sue A. full_name: Aicher, Sue A. last_name: Aicher - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: James S. full_name: Trimmer, James S. last_name: Trimmer citation: ama: Vierra NC, Ribeiro-Silva L, Kirmiz M, et al. Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA signaling. Nature Communications. 2023;14. doi:10.1038/s41467-023-40930-6 apa: Vierra, N. C., Ribeiro-Silva, L., Kirmiz, M., Van Der List, D., Bhandari, P., Mack, O. A., … Trimmer, J. S. (2023). Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA signaling. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-023-40930-6 chicago: Vierra, Nicholas C., Luisa Ribeiro-Silva, Michael Kirmiz, Deborah Van Der List, Pradeep Bhandari, Olivia A. Mack, James Carroll, et al. “Neuronal ER-Plasma Membrane Junctions Couple Excitation to Ca2+-Activated PKA Signaling.” Nature Communications. Springer Nature, 2023. https://doi.org/10.1038/s41467-023-40930-6. ieee: N. C. Vierra et al., “Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA signaling,” Nature Communications, vol. 14. Springer Nature, 2023. ista: Vierra NC, Ribeiro-Silva L, Kirmiz M, Van Der List D, Bhandari P, Mack OA, Carroll J, Le Monnier E, Aicher SA, Shigemoto R, Trimmer JS. 2023. Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA signaling. Nature Communications. 14, 5231. mla: Vierra, Nicholas C., et al. “Neuronal ER-Plasma Membrane Junctions Couple Excitation to Ca2+-Activated PKA Signaling.” Nature Communications, vol. 14, 5231, Springer Nature, 2023, doi:10.1038/s41467-023-40930-6. short: N.C. Vierra, L. Ribeiro-Silva, M. Kirmiz, D. Van Der List, P. Bhandari, O.A. Mack, J. Carroll, E. Le Monnier, S.A. Aicher, R. Shigemoto, J.S. Trimmer, Nature Communications 14 (2023). date_created: 2023-09-03T22:01:14Z date_published: 2023-08-26T00:00:00Z date_updated: 2025-09-09T12:50:49Z day: '26' ddc: - '570' department: - _id: RySh doi: 10.1038/s41467-023-40930-6 external_id: isi: - '001064563400013' pmid: - '37633939' file: - access_level: open_access checksum: 6ab8aab4e957f626a09a1c73db3388fb content_type: application/pdf creator: dernst date_created: 2023-09-06T06:50:07Z date_updated: 2023-09-06T06:50:07Z file_id: '14270' file_name: 2023_NatureComm_Vierra.pdf file_size: 9412549 relation: main_file success: 1 file_date_updated: 2023-09-06T06:50:07Z has_accepted_license: '1' intvolume: ' 14' isi: 1 language: - iso: eng month: '08' oa: 1 oa_version: Published Version pmid: 1 publication: Nature Communications publication_identifier: eissn: - 2041-1723 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA signaling 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: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 14 year: '2023' ... --- _id: '13173' abstract: - lang: eng text: GABAB receptor (GBR) activation inhibits neurotransmitter release in axon terminals in the brain, except in medial habenula (MHb) terminals, which show robust potentiation. However, mechanisms underlying this enigmatic potentiation remain elusive. Here, we report that GBR activation on MHb terminals induces an activity-dependent transition from a facilitating, tonic to a depressing, phasic neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked synaptic vesicles at the presynaptic active zone (AZ). Strikingly, tonic and phasic release exhibit distinct coupling distances and are selectively affected by deletion of synaptoporin (SPO) and Ca2+-dependent activator protein for secretion 2 (CAPS2), respectively. SPO modulates augmentation, the short-term plasticity associated with tonic release, and CAPS2 retains the increased RRP for initial responses in phasic response trains. Double pre-embedding immunolabeling confirmed the co-localization of CAPS2 and SPO inside the same terminal. The cytosolic protein CAPS2 showed a synaptic vesicle (SV)-associated distribution similar to the vesicular transmembrane protein SPO. A newly developed “Flash and Freeze-fracture” method revealed the release of SPO-associated vesicles in both tonic and phasic modes and activity-dependent recruitment of CAPS2 to the AZ during phasic release, which lasted several minutes. Overall, these results indicate that GBR activation translocates CAPS2 to the AZ along with the fusion of CAPS2-associated SVs, contributing to a persistent RRP increase. Thus, we discovered structural and molecular mechanisms underlying tonic and phasic neurotransmitter release and their transition by GBR activation in MHb terminals. article_processing_charge: No author: - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: ama: Shigemoto R. Transition from tonic to phasic neurotransmitter release by presynaptic GABAB receptor activation in medial habenula terminals. 2023. doi:10.15479/AT:ISTA:13173 apa: Shigemoto, R. (2023). Transition from tonic to phasic neurotransmitter release by presynaptic GABAB receptor activation in medial habenula terminals. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:13173 chicago: Shigemoto, Ryuichi. “Transition from Tonic to Phasic Neurotransmitter Release by Presynaptic GABAB Receptor Activation in Medial Habenula Terminals.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/AT:ISTA:13173. ieee: R. Shigemoto, “Transition from tonic to phasic neurotransmitter release by presynaptic GABAB receptor activation in medial habenula terminals.” Institute of Science and Technology Austria, 2023. ista: Shigemoto R. 2023. Transition from tonic to phasic neurotransmitter release by presynaptic GABAB receptor activation in medial habenula terminals, Institute of Science and Technology Austria, 10.15479/AT:ISTA:13173. mla: Shigemoto, Ryuichi. Transition from Tonic to Phasic Neurotransmitter Release by Presynaptic GABAB Receptor Activation in Medial Habenula Terminals. Institute of Science and Technology Austria, 2023, doi:10.15479/AT:ISTA:13173. short: R. Shigemoto, (2023). corr_author: '1' date_created: 2023-06-29T13:16:42Z date_published: 2023-07-29T00:00:00Z date_updated: 2025-09-04T12:16:24Z day: '29' ddc: - '571' department: - _id: RySh doi: 10.15479/AT:ISTA:13173 file: - access_level: closed checksum: ed59170869ba621f89f7c1894092192f content_type: application/x-zip-compressed creator: shigemot date_created: 2023-06-29T13:11:22Z date_updated: 2023-11-17T14:30:44Z description: After review an updated version of the data is provided file_id: '13174' file_name: Raw data for Koppensteiner et al.zip file_size: 542873672 relation: main_file title: Outdated Version - access_level: open_access checksum: c07860eb82b4d367245f1b589fe5c250 content_type: application/vnd.openxmlformats-officedocument.spreadsheetml.sheet creator: patrickd date_created: 2023-11-17T14:13:02Z date_updated: 2023-11-17T14:13:02Z file_id: '14550' file_name: 11-17-23 Updated Koppensteiner et al. raw data.xlsx file_size: 915079 relation: main_file success: 1 - access_level: open_access checksum: abf84b1699edac4349dc3a92d466fb7b content_type: application/x-zip-compressed creator: dernst date_created: 2024-02-06T07:21:43Z date_updated: 2024-02-06T07:21:43Z file_id: '14942' file_name: EM_Images.zip file_size: 544868924 relation: main_file success: 1 file_date_updated: 2024-02-06T07:21:43Z has_accepted_license: '1' keyword: - medial habenula - GABAB receptor - vesicle release - Flash and Freeze - Flash and Freeze-fracture month: '07' oa: 1 oa_version: Published Version publisher: Institute of Science and Technology Austria related_material: record: - id: '15084' relation: used_in_publication status: public status: public title: Transition from tonic to phasic neurotransmitter release by presynaptic GABAB receptor activation in medial habenula terminals tmp: image: /images/cc_by_nc.png legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) short: CC BY-NC (4.0) type: research_data user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2023' ... --- _id: '13202' abstract: - lang: eng text: Phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) plays an essential role in neuronal activities through interaction with various proteins involved in signaling at membranes. However, the distribution pattern of PI(4,5)P2 and the association with these proteins on the neuronal cell membranes remain elusive. In this study, we established a method for visualizing PI(4,5)P2 by SDS-digested freeze-fracture replica labeling (SDS-FRL) to investigate the quantitative nanoscale distribution of PI(4,5)P2 in cryo-fixed brain. We demonstrate that PI(4,5)P2 forms tiny clusters with a mean size of ∼1000 nm2 rather than randomly distributed in cerebellar neuronal membranes in male C57BL/6J mice. These clusters show preferential accumulation in specific membrane compartments of different cell types, in particular, in Purkinje cell (PC) spines and granule cell (GC) presynaptic active zones. Furthermore, we revealed extensive association of PI(4,5)P2 with CaV2.1 and GIRK3 across different membrane compartments, whereas its association with mGluR1α was compartment specific. These results suggest that our SDS-FRL method provides valuable insights into the physiological functions of PI(4,5)P2 in neurons. acknowledged_ssus: - _id: EM-Fac acknowledgement: This work was supported by The Institute of Science and Technology (IST) Austria, the European Union's Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie Grant Agreement No. 793482 (to K.E.) and by the European Research Council (ERC) Grant Agreement No. 694539 (to R.S.). We thank Nicoleta Condruz (IST Austria, Klosterneuburg, Austria) for technical assistance with sample preparation, the Electron Microscopy Facility of IST Austria (Klosterneuburg, Austria) for technical support with EM works, Natalia Baranova (University of Vienna, Vienna, Austria) and Martin Loose (IST Austria, Klosterneuburg, Austria) for advice on liposome preparation, and Yugo Fukazawa (University of Fukui, Fukui, Japan) for comments. article_processing_charge: No article_type: original author: - first_name: Kohgaku full_name: Eguchi, Kohgaku id: 2B7846DC-F248-11E8-B48F-1D18A9856A87 last_name: Eguchi orcid: 0000-0002-6170-2546 - first_name: Elodie full_name: Le Monnier, Elodie id: 3B59276A-F248-11E8-B48F-1D18A9856A87 last_name: Le Monnier - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: ama: Eguchi K, Le Monnier E, Shigemoto R. Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar neurons. The Journal of Neuroscience. 2023;43(23):4197-4216. doi:10.1523/JNEUROSCI.1514-22.2023 apa: Eguchi, K., Le Monnier, E., & Shigemoto, R. (2023). Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar neurons. The Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.1514-22.2023 chicago: Eguchi, Kohgaku, Elodie Le Monnier, and Ryuichi Shigemoto. “Nanoscale Phosphoinositide Distribution on Cell Membranes of Mouse Cerebellar Neurons.” The Journal of Neuroscience. Society for Neuroscience, 2023. https://doi.org/10.1523/JNEUROSCI.1514-22.2023. ieee: K. Eguchi, E. Le Monnier, and R. Shigemoto, “Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar neurons,” The Journal of Neuroscience, vol. 43, no. 23. Society for Neuroscience, pp. 4197–4216, 2023. ista: Eguchi K, Le Monnier E, Shigemoto R. 2023. Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar neurons. The Journal of Neuroscience. 43(23), 4197–4216. mla: Eguchi, Kohgaku, et al. “Nanoscale Phosphoinositide Distribution on Cell Membranes of Mouse Cerebellar Neurons.” The Journal of Neuroscience, vol. 43, no. 23, Society for Neuroscience, 2023, pp. 4197–216, doi:10.1523/JNEUROSCI.1514-22.2023. short: K. Eguchi, E. Le Monnier, R. Shigemoto, The Journal of Neuroscience 43 (2023) 4197–4216. corr_author: '1' date_created: 2023-07-09T22:01:12Z date_published: 2023-06-07T00:00:00Z date_updated: 2025-04-14T07:27:15Z day: '07' ddc: - '570' department: - _id: RySh doi: 10.1523/JNEUROSCI.1514-22.2023 ec_funded: 1 external_id: isi: - '001020132100005' pmid: - '37160366' file: - access_level: open_access checksum: 70b2141870e0bf1c94fd343e18fdbc32 content_type: application/pdf creator: alisjak date_created: 2023-07-10T09:04:58Z date_updated: 2023-07-10T09:04:58Z file_id: '13205' file_name: 2023_JN_Eguchi.pdf file_size: 7794425 relation: main_file success: 1 file_date_updated: 2023-07-10T09:04:58Z has_accepted_license: '1' intvolume: ' 43' isi: 1 issue: '23' language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: 4197-4216 pmid: 1 project: - _id: 2659CC84-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '793482' name: 'Ultrastructural analysis of phosphoinositides in nerve terminals: distribution, dynamics and physiological roles in synaptic transmission' - _id: 25CA28EA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '694539' name: 'In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour' publication: The Journal of Neuroscience publication_identifier: eissn: - 1529-2401 issn: - 0270-6474 publication_status: published publisher: Society for Neuroscience quality_controlled: '1' scopus_import: '1' status: public title: Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar neurons 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: 43 year: '2023' ... --- _id: '12212' abstract: - lang: eng text: Alzheimer’s disease (AD) is characterized by a reorganization of brain activity determining network hyperexcitability and loss of synaptic plasticity. Precisely, a dysfunction in metabotropic GABAB receptor signalling through G protein-gated inwardly rectifying K+ (GIRK or Kir3) channels on the hippocampus has been postulated. Thus, we determined the impact of amyloid-β (Aβ) pathology in GIRK channel density, subcellular distribution, and its association with GABAB receptors in hippocampal CA1 pyramidal neurons from the APP/PS1 mouse model using quantitative SDS-digested freeze-fracture replica labelling (SDS-FRL) and proximity ligation in situ assay (P-LISA). In wild type mice, single SDS-FRL detection revealed a similar dendritic gradient for GIRK1 and GIRK2 in CA1 pyramidal cells, with higher densities in spines, and GIRK3 showed a lower and uniform distribution. Double SDS-FRL showed a co-clustering of GIRK2 and GIRK1 in post- and presynaptic compartments, but not for GIRK2 and GIRK3. Likewise, double GABAB1 and GIRK2 SDS-FRL detection displayed a high degree of co-clustering in nanodomains (40–50 nm) mostly in spines and axon terminals. In APP/PS1 mice, the density of GIRK2 and GIRK1, but not for GIRK3, was significantly reduced along the neuronal surface of CA1 pyramidal cells and in axon terminals contacting them. Importantly, GABAB1 and GIRK2 co-clustering was not present in APP/PS1 mice. Similarly, P-LISA experiments revealed a significant reduction in GABAB1 and GIRK2 interaction on the hippocampus of this animal model. Overall, our results provide compelling evidence showing a significant reduction on the cell surface density of pre- and postsynaptic GIRK1 and GIRK2, but not GIRK3, and a decline in GABAB receptors and GIRK2 channels co-clustering in hippocampal pyramidal neurons from APP/PS1 mice, thus suggesting that a disruption in the GABAB receptor–GIRK channel membrane assembly causes dysregulation in the GABAB signalling via GIRK channels in this AD animal model. acknowledgement: "We thank Ms. Diane Latawiec for the English revision of the manuscript. Funding sources were the Spanish Ministerio de Economía y Competitividad, Junta de Comunidades de Castilla-La Mancha (Spain), and Life Science Innovation Center at University of Fukui. We thank Centres de Recerca de Catalunya (CERCA) Programme/Generalitat de Catalunya for IDIBELL institutional support. We thank Hitoshi Takagi and Takako Maegawa at the University of Fukui for their technical assistance on SDS-FRL experiments.\r\nThis work was supported by grants from the Spanish Ministerio de Economía y Competitividad (BFU2015-63769-R, RTI2018-095812-B-I00, and PID2021-125875OB-I00) and Junta de Comunidades de Castilla-La Mancha (SBPLY/17/180501/000229 and SBPLY/21/180501/000064) to RL, Life Science Innovation Center at University of Fukui and JSPS KAKENHI (Grant Numbers 16H04662, 19H03323, and 20H05058) to YF, and Margarita Salas fellowship from Ministerio de Universidades and Universidad de Castilla-La Mancha to AMB." article_number: '136' article_processing_charge: No article_type: original author: - first_name: Alejandro full_name: Martín-Belmonte, Alejandro last_name: Martín-Belmonte - first_name: Carolina full_name: Aguado, Carolina last_name: Aguado - first_name: Rocío full_name: Alfaro-Ruiz, Rocío last_name: Alfaro-Ruiz - first_name: Ana Esther full_name: Moreno-Martínez, Ana Esther last_name: Moreno-Martínez - first_name: Luis full_name: de la Ossa, Luis last_name: de la Ossa - first_name: Ester full_name: Aso, Ester last_name: Aso - first_name: Laura full_name: Gómez-Acero, Laura last_name: Gómez-Acero - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Yugo full_name: Fukazawa, Yugo last_name: Fukazawa - first_name: Francisco full_name: Ciruela, Francisco last_name: Ciruela - first_name: Rafael full_name: Luján, Rafael last_name: Luján citation: ama: Martín-Belmonte A, Aguado C, Alfaro-Ruiz R, et al. Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice. Alzheimer’s Research & Therapy. 2022;14. doi:10.1186/s13195-022-01078-5 apa: Martín-Belmonte, A., Aguado, C., Alfaro-Ruiz, R., Moreno-Martínez, A. E., de la Ossa, L., Aso, E., … Luján, R. (2022). Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice. Alzheimer’s Research & Therapy. Springer Nature. https://doi.org/10.1186/s13195-022-01078-5 chicago: Martín-Belmonte, Alejandro, Carolina Aguado, Rocío Alfaro-Ruiz, Ana Esther Moreno-Martínez, Luis de la Ossa, Ester Aso, Laura Gómez-Acero, et al. “Nanoscale Alterations in GABAB Receptors and GIRK Channel Organization on the Hippocampus of APP/PS1 Mice.” Alzheimer’s Research & Therapy. Springer Nature, 2022. https://doi.org/10.1186/s13195-022-01078-5. ieee: A. Martín-Belmonte et al., “Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice,” Alzheimer’s Research & Therapy, vol. 14. Springer Nature, 2022. ista: Martín-Belmonte A, Aguado C, Alfaro-Ruiz R, Moreno-Martínez AE, de la Ossa L, Aso E, Gómez-Acero L, Shigemoto R, Fukazawa Y, Ciruela F, Luján R. 2022. Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice. Alzheimer’s Research & Therapy. 14, 136. mla: Martín-Belmonte, Alejandro, et al. “Nanoscale Alterations in GABAB Receptors and GIRK Channel Organization on the Hippocampus of APP/PS1 Mice.” Alzheimer’s Research & Therapy, vol. 14, 136, Springer Nature, 2022, doi:10.1186/s13195-022-01078-5. short: A. Martín-Belmonte, C. Aguado, R. Alfaro-Ruiz, A.E. Moreno-Martínez, L. de la Ossa, E. Aso, L. Gómez-Acero, R. Shigemoto, Y. Fukazawa, F. Ciruela, R. Luján, Alzheimer’s Research & Therapy 14 (2022). date_created: 2023-01-16T09:45:51Z date_published: 2022-09-21T00:00:00Z date_updated: 2025-06-11T13:40:00Z day: '21' ddc: - '570' department: - _id: RySh doi: 10.1186/s13195-022-01078-5 external_id: isi: - '000857985500001' pmid: - '36131327' file: - access_level: open_access checksum: 88e49715ad6a1abf0fdb27efd65368dc content_type: application/pdf creator: dernst date_created: 2023-01-27T07:53:18Z date_updated: 2023-01-27T07:53:18Z file_id: '12413' file_name: 2022_AlzheimersResearch_MartinBelmont.pdf file_size: 11013325 relation: main_file success: 1 file_date_updated: 2023-01-27T07:53:18Z has_accepted_license: '1' intvolume: ' 14' isi: 1 keyword: - Cognitive Neuroscience - Neurology (clinical) - Neurology language: - iso: eng month: '09' oa: 1 oa_version: Published Version pmid: 1 publication: Alzheimer's Research & Therapy publication_identifier: issn: - 1758-9193 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 14 year: '2022' ... --- _id: '10889' abstract: - lang: eng text: Genetically encoded tags have introduced extensive lines of application from purification of tagged proteins to their visualization at the single molecular, cellular, histological and whole-body levels. Combined with other rapidly developing technologies such as clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system, proteomics, super-resolution microscopy and proximity labeling, a large variety of genetically encoded tags have been developed in the last two decades. In this review, I focus on the current status of tag development for electron microscopic (EM) visualization of proteins with metal particle labeling. Compared with conventional immunoelectron microscopy using gold particles, tag-mediated metal particle labeling has several advantages that could potentially improve the sensitivity, spatial and temporal resolution, and applicability to a wide range of proteins of interest (POIs). It may enable researchers to detect single molecules in situ, allowing the quantitative measurement of absolute numbers and exact localization patterns of POI in the ultrastructural context. Thus, genetically encoded tags for EM could revolutionize the field as green fluorescence protein did for light microscopy, although we still have many challenges to overcome before reaching this goal. acknowledgement: European Research Council Advanced Grant (694539 to R.S.). article_processing_charge: No article_type: original author: - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: ama: Shigemoto R. Electron microscopic visualization of single molecules by tag-mediated metal particle labeling. Microscopy. 2022;71(Supplement_1):i72-i80. doi:10.1093/jmicro/dfab048 apa: Shigemoto, R. (2022). Electron microscopic visualization of single molecules by tag-mediated metal particle labeling. Microscopy. Oxford University Press. https://doi.org/10.1093/jmicro/dfab048 chicago: Shigemoto, Ryuichi. “Electron Microscopic Visualization of Single Molecules by Tag-Mediated Metal Particle Labeling.” Microscopy. Oxford University Press, 2022. https://doi.org/10.1093/jmicro/dfab048. ieee: R. Shigemoto, “Electron microscopic visualization of single molecules by tag-mediated metal particle labeling,” Microscopy, vol. 71, no. Supplement_1. Oxford University Press, pp. i72–i80, 2022. ista: Shigemoto R. 2022. Electron microscopic visualization of single molecules by tag-mediated metal particle labeling. Microscopy. 71(Supplement_1), i72–i80. mla: Shigemoto, Ryuichi. “Electron Microscopic Visualization of Single Molecules by Tag-Mediated Metal Particle Labeling.” Microscopy, vol. 71, no. Supplement_1, Oxford University Press, 2022, pp. i72–80, doi:10.1093/jmicro/dfab048. short: R. Shigemoto, Microscopy 71 (2022) i72–i80. corr_author: '1' date_created: 2022-03-20T23:01:39Z date_published: 2022-03-01T00:00:00Z date_updated: 2025-05-14T11:05:40Z day: '01' department: - _id: RySh doi: 10.1093/jmicro/dfab048 ec_funded: 1 external_id: isi: - '000768384100011' pmid: - '35275179' intvolume: ' 71' isi: 1 issue: Supplement_1 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1093/jmicro/dfab048 month: '03' oa: 1 oa_version: Published Version page: i72-i80 pmid: 1 project: - _id: 25CA28EA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '694539' name: 'In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour' publication: Microscopy publication_identifier: eissn: - 2050-5701 issn: - 2050-5698 publication_status: published publisher: Oxford University Press quality_controlled: '1' scopus_import: '1' status: public title: Electron microscopic visualization of single molecules by tag-mediated metal particle labeling type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 71 year: '2022' ... --- _id: '10890' abstract: - lang: eng text: Upon the arrival of action potentials at nerve terminals, neurotransmitters are released from synaptic vesicles (SVs) by exocytosis. CaV2.1, 2.2, and 2.3 are the major subunits of the voltage-gated calcium channel (VGCC) responsible for increasing intraterminal calcium levels and triggering SV exocytosis in the central nervous system (CNS) synapses. The two-dimensional analysis of CaV2 distributions using sodium dodecyl sulfate (SDS)-digested freeze-fracture replica labeling (SDS-FRL) has revealed their numbers, densities, and nanoscale clustering patterns in individual presynaptic active zones. The variation in these properties affects the coupling of VGCCs with calcium sensors on SVs, synaptic efficacy, and temporal precision of transmission. In this study, we summarize how the morphological parameters of CaV2 distribution obtained using SDS-FRL differ depending on the different types of synapses and could correspond to functional properties in synaptic transmission. acknowledgement: "This work was supported by the European Research Council advanced grant No. 694539 and the joint German-Austrian DFG and FWF project SYNABS (FWF: I-4638-B) to RS.\r\nThe authors thank Walter Kaufmann for his critical comments on the manuscript." article_number: '846615' article_processing_charge: No article_type: original author: - first_name: Kohgaku full_name: Eguchi, Kohgaku id: 2B7846DC-F248-11E8-B48F-1D18A9856A87 last_name: Eguchi orcid: 0000-0002-6170-2546 - first_name: Jacqueline-Claire full_name: Montanaro-Punzengruber, Jacqueline-Claire id: 3786AB44-F248-11E8-B48F-1D18A9856A87 last_name: Montanaro-Punzengruber - first_name: Elodie full_name: Le Monnier, Elodie id: 3B59276A-F248-11E8-B48F-1D18A9856A87 last_name: Le Monnier - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: ama: Eguchi K, Montanaro-Punzengruber J-C, Le Monnier E, Shigemoto R. The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals. Frontiers in Neuroanatomy. 2022;16. doi:10.3389/fnana.2022.846615 apa: Eguchi, K., Montanaro-Punzengruber, J.-C., Le Monnier, E., & Shigemoto, R. (2022). The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals. Frontiers in Neuroanatomy. Frontiers. https://doi.org/10.3389/fnana.2022.846615 chicago: Eguchi, Kohgaku, Jacqueline-Claire Montanaro-Punzengruber, Elodie Le Monnier, and Ryuichi Shigemoto. “The Number and Distinct Clustering Patterns of Voltage-Gated Calcium Channels in Nerve Terminals.” Frontiers in Neuroanatomy. Frontiers, 2022. https://doi.org/10.3389/fnana.2022.846615. ieee: K. Eguchi, J.-C. Montanaro-Punzengruber, E. Le Monnier, and R. Shigemoto, “The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals,” Frontiers in Neuroanatomy, vol. 16. Frontiers, 2022. ista: Eguchi K, Montanaro-Punzengruber J-C, Le Monnier E, Shigemoto R. 2022. The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals. Frontiers in Neuroanatomy. 16, 846615. mla: Eguchi, Kohgaku, et al. “The Number and Distinct Clustering Patterns of Voltage-Gated Calcium Channels in Nerve Terminals.” Frontiers in Neuroanatomy, vol. 16, 846615, Frontiers, 2022, doi:10.3389/fnana.2022.846615. short: K. Eguchi, J.-C. Montanaro-Punzengruber, E. Le Monnier, R. Shigemoto, Frontiers in Neuroanatomy 16 (2022). corr_author: '1' date_created: 2022-03-20T23:01:39Z date_published: 2022-02-24T00:00:00Z date_updated: 2026-04-16T08:18:54Z day: '24' ddc: - '570' department: - _id: RySh doi: 10.3389/fnana.2022.846615 ec_funded: 1 external_id: isi: - '000766662700001' pmid: - '35280978' file: - access_level: open_access checksum: 51ec9b90e7da919e22c01a15489eaacd content_type: application/pdf creator: dernst date_created: 2022-03-21T09:41:19Z date_updated: 2022-03-21T09:41:19Z file_id: '10911' file_name: 2022_FrontiersNeuroanatomy_Eguchi.pdf file_size: 2416395 relation: main_file success: 1 file_date_updated: 2022-03-21T09:41:19Z has_accepted_license: '1' intvolume: ' 16' isi: 1 language: - iso: eng month: '02' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 25CA28EA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '694539' name: 'In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour' - _id: 05970B30-7A3F-11EA-A408-12923DDC885E grant_number: I04638 name: LGI1 antibody-induced pathophysiology in synapses publication: Frontiers in Neuroanatomy publication_identifier: eissn: - 1662-5129 publication_status: published publisher: Frontiers quality_controlled: '1' scopus_import: '1' status: public title: The number and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals 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: ba8df636-2132-11f1-aed0-ed93e2281fdd volume: 16 year: '2022' ... --- _id: '10051' abstract: - lang: eng text: 'Rab-interacting molecule (RIM)-binding protein 2 (BP2) is a multidomain protein of the presynaptic active zone (AZ). By binding to RIM, bassoon (Bsn), and voltage-gated Ca2+ channels (CaV), it is considered to be a central organizer of the topography of CaV and release sites of synaptic vesicles (SVs) at the AZ. Here, we used RIM-BP2 knock-out (KO) mice and their wild-type (WT) littermates of either sex to investigate the role of RIM-BP2 at the endbulb of Held synapse of auditory nerve fibers (ANFs) with bushy cells (BCs) of the cochlear nucleus, a fast relay of the auditory pathway with high release probability. Disruption of RIM-BP2 lowered release probability altering short-term plasticity and reduced evoked EPSCs. Analysis of SV pool dynamics during high-frequency train stimulation indicated a reduction of SVs with high release probability but an overall normal size of the readily releasable SV pool (RRP). The Ca2+-dependent fast component of SV replenishment after RRP depletion was slowed. Ultrastructural analysis by superresolution light and electron microscopy revealed an impaired topography of presynaptic CaV and a reduction of docked and membrane-proximal SVs at the AZ. We conclude that RIM-BP2 organizes the topography of CaV, and promotes SV tethering and docking. This way RIM-BP2 is critical for establishing a high initial release probability as required to reliably signal sound onset information that we found to be degraded in BCs of RIM-BP2-deficient mice in vivo. SIGNIFICANCE STATEMENT: Rab-interacting molecule (RIM)-binding proteins (BPs) are key organizers of the active zone (AZ). Using a multidisciplinary approach to the calyceal endbulb of Held synapse that transmits auditory information at rates of up to hundreds of Hertz with submillisecond precision we demonstrate a requirement for RIM-BP2 for normal auditory signaling. Endbulb synapses lacking RIM-BP2 show a reduced release probability despite normal whole-terminal Ca2+ influx and abundance of the key priming protein Munc13-1, a reduced rate of SV replenishment, as well as an altered topography of voltage-gated (CaV)2.1 Ca2+ channels, and fewer docked and membrane proximal synaptic vesicles (SVs). This hampers transmission of sound onset information likely affecting downstream neural computations such as of sound localization.' acknowledgement: This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) through the Collaborative Sensory Research Center 1286 [to C.W. (A4) and T.M. (B5)] and under Germany’s Excellence Strategy Grant EXC 2067/1-390729940. We thank S. Gerke, A.J. Goldak, and C. Senger-Freitag for expert technical assistance; G. Hoch for developing image analysis routines; and S. Chepurwar and N. Strenzke for technical support and discussion regarding in vivo experiments. We also thank Dr. Christian Rosenmund, Dr. Katharina Grauel, and Dr. Stephan Sigrist for providing RIM-BP2 KO mice and Dr. Masahiko Watanabe for providing the anti-neurexin-antibody, and Dr. Toshihisa Ohtsuka for the anti-ELKS-antibody. J. Neef for help with the STED imaging and image analysis; E. Neher and S. Rizzoli for discussion and comments on the manuscript; K. Eguchi for help with the statistical analysis; and C. H. Huang and J. Neef for constant support and scientific discussion. article_processing_charge: No article_type: original author: - first_name: Tanvi full_name: Butola, Tanvi last_name: Butola - first_name: Theocharis full_name: Alvanos, Theocharis last_name: Alvanos - first_name: Anika full_name: Hintze, Anika last_name: Hintze - first_name: Peter full_name: Koppensteiner, Peter id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87 last_name: Koppensteiner orcid: 0000-0002-3509-1948 - first_name: David full_name: Kleindienst, David id: 42E121A4-F248-11E8-B48F-1D18A9856A87 last_name: Kleindienst - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Carolin full_name: Wichmann, Carolin last_name: Wichmann - first_name: Tobias full_name: Moser, Tobias last_name: Moser citation: ama: Butola T, Alvanos T, Hintze A, et al. RIM-binding protein 2 organizes Ca21 channel topography and regulates release probability and vesicle replenishment at a fast central synapse. Journal of Neuroscience. 2021;41(37):7742-7767. doi:10.1523/JNEUROSCI.0586-21.2021 apa: Butola, T., Alvanos, T., Hintze, A., Koppensteiner, P., Kleindienst, D., Shigemoto, R., … Moser, T. (2021). RIM-binding protein 2 organizes Ca21 channel topography and regulates release probability and vesicle replenishment at a fast central synapse. Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.0586-21.2021 chicago: Butola, Tanvi, Theocharis Alvanos, Anika Hintze, Peter Koppensteiner, David Kleindienst, Ryuichi Shigemoto, Carolin Wichmann, and Tobias Moser. “RIM-Binding Protein 2 Organizes Ca21 Channel Topography and Regulates Release Probability and Vesicle Replenishment at a Fast Central Synapse.” Journal of Neuroscience. Society for Neuroscience, 2021. https://doi.org/10.1523/JNEUROSCI.0586-21.2021. ieee: T. Butola et al., “RIM-binding protein 2 organizes Ca21 channel topography and regulates release probability and vesicle replenishment at a fast central synapse,” Journal of Neuroscience, vol. 41, no. 37. Society for Neuroscience, pp. 7742–7767, 2021. ista: Butola T, Alvanos T, Hintze A, Koppensteiner P, Kleindienst D, Shigemoto R, Wichmann C, Moser T. 2021. RIM-binding protein 2 organizes Ca21 channel topography and regulates release probability and vesicle replenishment at a fast central synapse. Journal of Neuroscience. 41(37), 7742–7767. mla: Butola, Tanvi, et al. “RIM-Binding Protein 2 Organizes Ca21 Channel Topography and Regulates Release Probability and Vesicle Replenishment at a Fast Central Synapse.” Journal of Neuroscience, vol. 41, no. 37, Society for Neuroscience, 2021, pp. 7742–67, doi:10.1523/JNEUROSCI.0586-21.2021. short: T. Butola, T. Alvanos, A. Hintze, P. Koppensteiner, D. Kleindienst, R. Shigemoto, C. Wichmann, T. Moser, Journal of Neuroscience 41 (2021) 7742–7767. date_created: 2021-09-27T14:33:13Z date_published: 2021-09-15T00:00:00Z date_updated: 2023-08-14T06:56:30Z day: '15' ddc: - '570' department: - _id: RySh doi: 10.1523/JNEUROSCI.0586-21.2021 external_id: isi: - '000752287700005' pmid: - '34353898' file: - access_level: open_access checksum: 769ab627c7355a50ccfd445e43a5f351 content_type: application/pdf creator: dernst date_created: 2022-05-31T09:10:15Z date_updated: 2022-05-31T09:10:15Z file_id: '11423' file_name: 2021_JourNeuroscience_Butola.pdf file_size: 11571961 relation: main_file success: 1 file_date_updated: 2022-05-31T09:10:15Z has_accepted_license: '1' intvolume: ' 41' isi: 1 issue: '37' language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: 7742-7767 pmid: 1 publication: Journal of Neuroscience publication_identifier: eissn: - 1529-2401 issn: - 0270-6474 publication_status: published publisher: Society for Neuroscience quality_controlled: '1' scopus_import: '1' status: public title: RIM-binding protein 2 organizes Ca21 channel topography and regulates release probability and vesicle replenishment at a fast central synapse 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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 41 year: '2021' ... --- _id: '10403' abstract: - lang: eng text: Synaptic transmission, connectivity, and dendritic morphology mature in parallel during brain development and are often disrupted in neurodevelopmental disorders. Yet how these changes influence the neuronal computations necessary for normal brain function are not well understood. To identify cellular mechanisms underlying the maturation of synaptic integration in interneurons, we combined patch-clamp recordings of excitatory inputs in mouse cerebellar stellate cells (SCs), three-dimensional reconstruction of SC morphology with excitatory synapse location, and biophysical modeling. We found that postnatal maturation of postsynaptic strength was homogeneously reduced along the somatodendritic axis, but dendritic integration was always sublinear. However, dendritic branching increased without changes in synapse density, leading to a substantial gain in distal inputs. Thus, changes in synapse distribution, rather than dendrite cable properties, are the dominant mechanism underlying the maturation of neuronal computation. These mechanisms favor the emergence of a spatially compartmentalized two-stage integration model promoting location-dependent integration within dendritic subunits. acknowledgement: This study was supported by the Centre National de la Recherche Scientifique and the Agence Nationale de la Recherche (ANR-13-BSV4-00166, to LC and DAD). TA was supported by fellowships from the Fondation pour la Recherche Medicale and the Swedish Research Council. We thank Dmitry Ershov from the Image Analysis Hub of the Institut Pasteur, Elodie Le Monnier, Elena Hollergschwandtner, Vanessa Zheden, and Corinne Nantet for technical support and Haining Zhong for providing the Venus-tagged PSD95 mouse line. We would like to thank Alberto Bacci, Ann Lohof, and Nelson Rebola for comments on the manuscript. article_number: e65954 article_processing_charge: No article_type: original author: - first_name: Celia full_name: Biane, Celia last_name: Biane - first_name: Florian full_name: Rückerl, Florian last_name: Rückerl - first_name: Therese full_name: Abrahamsson, Therese last_name: Abrahamsson - first_name: Cécile full_name: Saint-Cloment, Cécile last_name: Saint-Cloment - first_name: Jean full_name: Mariani, Jean last_name: Mariani - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: David A. full_name: Digregorio, David A. last_name: Digregorio - first_name: Rachel M. full_name: Sherrard, Rachel M. last_name: Sherrard - first_name: Laurence full_name: Cathala, Laurence last_name: Cathala citation: ama: Biane C, Rückerl F, Abrahamsson T, et al. Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons. eLife. 2021;10. doi:10.7554/eLife.65954 apa: Biane, C., Rückerl, F., Abrahamsson, T., Saint-Cloment, C., Mariani, J., Shigemoto, R., … Cathala, L. (2021). Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.65954 chicago: Biane, Celia, Florian Rückerl, Therese Abrahamsson, Cécile Saint-Cloment, Jean Mariani, Ryuichi Shigemoto, David A. Digregorio, Rachel M. Sherrard, and Laurence Cathala. “Developmental Emergence of Two-Stage Nonlinear Synaptic Integration in Cerebellar Interneurons.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/eLife.65954. ieee: C. Biane et al., “Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons,” eLife, vol. 10. eLife Sciences Publications, 2021. ista: Biane C, Rückerl F, Abrahamsson T, Saint-Cloment C, Mariani J, Shigemoto R, Digregorio DA, Sherrard RM, Cathala L. 2021. Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons. eLife. 10, e65954. mla: Biane, Celia, et al. “Developmental Emergence of Two-Stage Nonlinear Synaptic Integration in Cerebellar Interneurons.” ELife, vol. 10, e65954, eLife Sciences Publications, 2021, doi:10.7554/eLife.65954. short: C. Biane, F. Rückerl, T. Abrahamsson, C. Saint-Cloment, J. Mariani, R. Shigemoto, D.A. Digregorio, R.M. Sherrard, L. Cathala, ELife 10 (2021). date_created: 2021-12-05T23:01:40Z date_published: 2021-11-03T00:00:00Z date_updated: 2025-03-07T08:12:39Z day: '03' ddc: - '570' department: - _id: RySh doi: 10.7554/eLife.65954 external_id: isi: - '000715789500001' pmid: - '34730085' file: - access_level: open_access checksum: c7c33c3319428d56e332e22349c50ed3 content_type: application/pdf creator: cchlebak date_created: 2021-12-10T08:31:41Z date_updated: 2021-12-10T08:31:41Z file_id: '10528' file_name: 2021_eLife_Biane.pdf file_size: 13131322 relation: main_file success: 1 file_date_updated: 2021-12-10T08:31:41Z has_accepted_license: '1' intvolume: ' 10' isi: 1 language: - iso: eng month: '11' oa: 1 oa_version: Published Version pmid: 1 publication: eLife publication_identifier: eissn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: Developmental emergence of two-stage nonlinear synaptic integration in cerebellar interneurons 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: 10 year: '2021' ...