--- DOAJ_listed: '1' OA_place: publisher OA_type: gold PlanS_conform: '1' _id: '22615' abstract: - lang: eng text: "Background and Objectives: \r\nAnti-immunoglobulin-like cell adhesion molecule 5 (IgLON5) disease is a novel and poten-\r\ntially treatable entity. Therefore, it is important to recognize all clinical symptoms and di-\r\nagnostic clues. We specifically investigated neuromuscular signs and symptoms and muscle biopsy pathology, providing a link between IgLON5 and clinical features of myopathy.\r\nMethods: \r\nAll patients diagnosed with anti-IgLON5 disease in the Netherlands between 2016 and 2023 were included. Serum and CSF samples were tested with immunohistochemistry on rat brain and in-house cell-based assay using live cells. Biopsies of the vastus lateralis muscle were performed in patients with neuromuscular signs and symptoms and analyzed in Vienna to-\r\ngether with 3 biopsies of non-Dutch patients sent to Vienna for second opinion.\r\nResults: \r\nTwenty patients with anti-IgLON5 disease were included (10 male, 50%). The median age at onset was 61.5 years (range 45–85), and the median time from onset to diagnosis was 30 months (range 3–280). Neuromuscular symptoms were present in over half of the patients (11/20), including proximal limb weakness (n = 11), axial weakness (n = 1), muscle atrophy (n = 6), and fasciculations (n = 5). All 12 muscle biopsies (9 from the Dutch cohort, 3 external) showed mild myopathic alterations, 2 additionally presented target fibers and fiber type grouping (compatible with neu-\r\nrogenic myopathy), and 3 patients showed immune cell infiltration. We found a strong upregulation of IgLON5 expression in muscle fibers in all patients and also in different muscle disease controls, while immunoreactivity in healthy control muscle was faint/absent.\r\nDiscussion: \r\nOur data support that IgLON5 might play a role in muscle regeneration, which might result in proximal myopathy as a prominent clinical feature in anti-IgLON5 disease. This finding broadens the clinical phenotype of anti-IgLON5 disease and can be an important clue for earlier diagnosis and start of immunotherapy." acknowledgement: "One author (Manuela Paunovic) was removed from the paper due to personal circumstances. Her contributions were removed from the manuscript before final review. The authors thank all patients for their participation and all referring physicians. The authors thank Professor Joachim Weis at the Medical Faculty RWTH Aachen University for his contribution to the manuscript. The authors would like to thank Andrea Polt and Irene Erber at the Medical University of Vienna, and Jacqueline Montanaro at IST Austria, for their assistance in the laboratory. N.A.M.E. van der Beek participates in EURO-NMD. M.W.J. Schreurs, P.A.E. Sillevis Smitt, J.M. de Vries, and M.J. Titulaer are members of the European Reference Network for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases–Project ID No 739543 (ERN-RITA; HCP Erasmus MC). IK was funded by the Austrian Science Fund (FWF, T996-B30). RS was funded by the Austrian Science Fund (FWF, SYNABS, I6565-B). JL was funded by German Federal Ministry of Education and Research (BMBF, Forschungsverbund CONNECT-GEN-\r\nERATE, 01 GM2208B). RvS was funded by AEA Seed Grant 2023 and InterAct Grant of Alzheimer Nederland 2023. LS was funded by Instituto de Salud Carlos III (ISCIII, PI21/ 00165) and the Networking Support Scheme funded from the European Union’s Horizon 2020 research and innovation program (EJP RD COFUND-EJP N° 825575). JdV was funded by AEA Seed Grant 2021. RH was funded by grants from the Austrian Science Fund (FWF, SYNABS, I4685-B, I6565-B), Forschungsf¨orderungsgesellschaft (FFG, IGNITE-\r\nMIND, FO999920011), and the Austrian Society of\r\nNeurology (\r\n¨\r\nOsterreichische Gesellschaft f¨ur Neurologie).\r\nMT was funded by the Dutch EpilepsieNL Foundation (NEF 19-08), an Interlaken Leadership award, Dioraphte (2001 0403) the Dutch Research Council (ZonMW, PARADE-\r\nVIMP) and E-RARE JTC 2018 (UltraAIE, 90030376505)." article_processing_charge: Yes article_type: original author: - first_name: Yvette S. full_name: Crijnen, Yvette S. last_name: Crijnen - first_name: Verena full_name: Endmayr, Verena last_name: Endmayr - first_name: Suzanne C. full_name: Franken, Suzanne C. last_name: Franken - first_name: Nadine A.M.E. full_name: Van Der Beek, Nadine A.M.E. last_name: Van Der Beek - first_name: Maartje full_name: Louter, Maartje last_name: Louter - first_name: Thomas full_name: Ströbel, Thomas last_name: Ströbel - first_name: Ellen full_name: Gelpi, Ellen last_name: Gelpi - first_name: Inga full_name: Koneczny, Inga last_name: Koneczny - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Jan full_name: Lewerenz, Jan last_name: Lewerenz - first_name: Birgit full_name: Högl, Birgit last_name: Högl - first_name: Julia V. full_name: Wanschitz, Julia V. last_name: Wanschitz - first_name: Ulrich He full_name: Hofstadt-Van Oy, Ulrich He last_name: Hofstadt-Van Oy - first_name: Robin W. full_name: Van Steenhoven, Robin W. last_name: Van Steenhoven - first_name: Mariska M.P. full_name: Nagtzaam, Mariska M.P. last_name: Nagtzaam - first_name: Jeroen full_name: Kerstens, Jeroen last_name: Kerstens - first_name: Juliette full_name: Brenner, Juliette last_name: Brenner - first_name: Anna E.M. full_name: Bastiaansen, Anna E.M. last_name: Bastiaansen - first_name: Robert M. full_name: Verdijk, Robert M. last_name: Verdijk - first_name: Thierry P.P. full_name: Van Den Bosch, Thierry P.P. last_name: Van Den Bosch - first_name: Marco full_name: Schreurs, Marco last_name: Schreurs - first_name: Sharon full_name: Veenbergen, Sharon last_name: Veenbergen - first_name: Marcel M. full_name: Verbeek, Marcel M. last_name: Verbeek - first_name: Dave L. full_name: Roelen, Dave L. last_name: Roelen - first_name: Mar full_name: Guasp, Mar last_name: Guasp - first_name: Peter A.E. full_name: Sillevis Smitt, Peter A.E. last_name: Sillevis Smitt - first_name: Lidia full_name: Sabater, Lidia last_name: Sabater - first_name: Juna M. full_name: De Vries, Juna M. last_name: De Vries - first_name: Romana full_name: Höftberger, Romana last_name: Höftberger - first_name: Maarten J. full_name: Titulaer, Maarten J. last_name: Titulaer citation: ama: Crijnen YS, Endmayr V, Franken SC, et al. Muscle regeneration failure may lead to clinical features of myopathy in anti-IgLON5 disease. Neurology, Neuroimmunology & Neuroinflammation. 2026;13(5):e200525. doi:10.1212/NXI.0000000000200525 apa: Crijnen, Y. S., Endmayr, V., Franken, S. C., Van Der Beek, N. A. M. E., Louter, M., Ströbel, T., … Titulaer, M. J. (2026). Muscle regeneration failure may lead to clinical features of myopathy in anti-IgLON5 disease. Neurology, Neuroimmunology & Neuroinflammation. Wolters Kluwer. https://doi.org/10.1212/NXI.0000000000200525 chicago: Crijnen, Yvette S., Verena Endmayr, Suzanne C. Franken, Nadine A.M.E. Van Der Beek, Maartje Louter, Thomas Ströbel, Ellen Gelpi, et al. “Muscle Regeneration Failure May Lead to Clinical Features of Myopathy in Anti-IgLON5 Disease.” Neurology, Neuroimmunology & Neuroinflammation. Wolters Kluwer, 2026. https://doi.org/10.1212/NXI.0000000000200525. ieee: Y. S. Crijnen et al., “Muscle regeneration failure may lead to clinical features of myopathy in anti-IgLON5 disease,” Neurology, Neuroimmunology & Neuroinflammation, vol. 13, no. 5. Wolters Kluwer, p. e200525, 2026. ista: Crijnen YS, Endmayr V, Franken SC, Van Der Beek NAME, Louter M, Ströbel T, Gelpi E, Koneczny I, Shigemoto R, Lewerenz J, Högl B, Wanschitz JV, Hofstadt-Van Oy UH, Van Steenhoven RW, Nagtzaam MMP, Kerstens J, Brenner J, Bastiaansen AEM, Verdijk RM, Van Den Bosch TPP, Schreurs M, Veenbergen S, Verbeek MM, Roelen DL, Guasp M, Sillevis Smitt PAE, Sabater L, De Vries JM, Höftberger R, Titulaer MJ. 2026. Muscle regeneration failure may lead to clinical features of myopathy in anti-IgLON5 disease. Neurology, Neuroimmunology & Neuroinflammation. 13(5), e200525. mla: Crijnen, Yvette S., et al. “Muscle Regeneration Failure May Lead to Clinical Features of Myopathy in Anti-IgLON5 Disease.” Neurology, Neuroimmunology & Neuroinflammation, vol. 13, no. 5, Wolters Kluwer, 2026, p. e200525, doi:10.1212/NXI.0000000000200525. short: Y.S. Crijnen, V. Endmayr, S.C. Franken, N.A.M.E. Van Der Beek, M. Louter, T. Ströbel, E. Gelpi, I. Koneczny, R. Shigemoto, J. Lewerenz, B. Högl, J.V. Wanschitz, U.H. Hofstadt-Van Oy, R.W. Van Steenhoven, M.M.P. Nagtzaam, J. Kerstens, J. Brenner, A.E.M. Bastiaansen, R.M. Verdijk, T.P.P. Van Den Bosch, M. Schreurs, S. Veenbergen, M.M. Verbeek, D.L. Roelen, M. Guasp, P.A.E. Sillevis Smitt, L. Sabater, J.M. De Vries, R. Höftberger, M.J. Titulaer, Neurology, Neuroimmunology & Neuroinflammation 13 (2026) e200525. das_tickbox: '1' dataavailabilitystatement: Any data not published within this article are available at Erasmus MC, Rotterdam, and Medical University of Vienna. Data will be shared on reasonable request from any qualified investigator, ascertaining anonymization of the individual patients, in line with European privacy regulations. date_created: 2026-08-02T22:01:52Z date_published: 2026-09-01T00:00:00Z date_updated: 2026-08-03T08:16:04Z day: '01' ddc: - '570' department: - _id: RySh doi: 10.1212/NXI.0000000000200525 external_id: pmid: - '42441930' file: - access_level: open_access checksum: 7cc4c4c180a2cf65603a02bef7b75784 content_type: application/pdf creator: dernst date_created: 2026-08-03T08:06:16Z date_updated: 2026-08-03T08:06:16Z file_id: '22631' file_name: 2026_Neurology_Crijnen.pdf file_size: 1122644 relation: main_file success: 1 file_date_updated: 2026-08-03T08:06:16Z fulldoi: https://doi.org/10.1212/NXI.0000000000200525 has_accepted_license: '1' intvolume: ' 13' issue: '5' language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '09' oa: 1 oa_version: Published Version page: e200525 pmid: 1 project: - _id: 05970B30-7A3F-11EA-A408-12923DDC885E grant_number: I04638 name: LGI1 antibody-induced pathophysiology in synapses publication: Neurology, Neuroimmunology & Neuroinflammation publication_identifier: eissn: - 2332-7812 publication_status: published publisher: Wolters Kluwer quality_controlled: '1' researchdata_availability: upon request scopus_import: '1' status: public supplementarymaterial: no title: Muscle regeneration failure may lead to clinical features of myopathy in anti-IgLON5 disease 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: 13 year: '2026' ... --- OA_place: publisher OA_type: hybrid _id: '22913' abstract: - lang: eng text: The medial habenula (MHb) is implicated in regulating emotional responses to aversive events. Studies in zebrafish have identified a remarkable morphological left–right asymmetry in the dorsal habenula (zebrafish equivalent of mammalian MHb)-interpeduncular nucleus (IPN) pathway and its asymmetrical roles in behavior. However, there is little evidence for structural or functional lateralization in the mammalian MHb-IPN pathway. Here, we investigated the synaptic properties of left- and right-MHb afferents to the IPN and their roles in the expression of conditioned fear in mice. We found that each IPN neuron receives inputs from both left and right MHb, but the left MHb-originating synapses exhibit lower release probability and higher γ-aminobutyric acid type B receptor (GABABR)-mediated potentiation compared to the right MHb-originating synapses. Interestingly, these asymmetrical properties persist in the inversus visceral mutant mice with normal internal organ laterality (situs solitus), but nearly disappear in those with reversed internal organ laterality (situs inversus). Behaviorally, chemogenetic inhibition of cholinergic neurons and conditional deletion of GABABR in the left, but not the right, MHb significantly attenuated cue-dependent fear recall. Our results demonstrate functional asymmetry of the MHb under partial influence of the nodal flow in mice, revealing a predominant role of GABABR-mediated signaling in the left MHb-IPN pathway in modulating fear memories. These findings suggest that lateralized MHb pathways could represent a fundamental principle in the neural regulation of emotion across species but that they develop differently in zebrafish and mice. acknowledged_ssus: - _id: M-Shop - _id: PreCl acknowledgement: We thank Bernhard Bettler for GABAB1 floxed mice. This project has received funding from the Austrian Science Fund (10.55776/PAT5720324) to R.S., and the Marie Skłodowska-Curie Grant Agreement No. 665385 to C.Ö. We thank Todor Asenov from the ISTA machine shop for preparing the custom part and the ISTA preclinical facility for animal care. SI Appendix, Fig. S7 was created in BioRender under the following license [Onal, C.(2026) https://BioRender.com/wuyvshe]. For open access purposes, the author has applied a CC BY-NC-ND public copyright license to any author-accepted manuscript version arising from this submission. article_number: e2536560123 article_processing_charge: Yes (in subscription journal) article_type: original author: - 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: Peter full_name: Koppensteiner, Peter id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87 last_name: Koppensteiner orcid: 0000-0002-3509-1948 - first_name: Mary W full_name: Muhia, Mary W id: ab7ed20f-09f7-11eb-909c-d5d0b443ee9d last_name: Muhia - 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: Önal C, Koppensteiner P, Muhia MW, Le Monnier E, Shigemoto R. Asymmetrical modulation of fear expression via GABAB receptors in the mouse medial habenula. Proceedings of the National Academy of Sciences of the United States of America. 2026;123(36). doi:10.1073/pnas.2536560123 apa: Önal, C., Koppensteiner, P., Muhia, M. W., Le Monnier, E., & Shigemoto, R. (2026). Asymmetrical modulation of fear expression via GABAB receptors in the mouse medial habenula. Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences. https://doi.org/10.1073/pnas.2536560123 chicago: Önal, Cihan, Peter Koppensteiner, Mary W Muhia, Elodie Le Monnier, and Ryuichi Shigemoto. “Asymmetrical Modulation of Fear Expression via GABAB Receptors in the Mouse Medial Habenula.” Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 2026. https://doi.org/10.1073/pnas.2536560123. ieee: C. Önal, P. Koppensteiner, M. W. Muhia, E. Le Monnier, and R. Shigemoto, “Asymmetrical modulation of fear expression via GABAB receptors in the mouse medial habenula,” Proceedings of the National Academy of Sciences of the United States of America, vol. 123, no. 36. National Academy of Sciences, 2026. ista: Önal C, Koppensteiner P, Muhia MW, Le Monnier E, Shigemoto R. 2026. Asymmetrical modulation of fear expression via GABAB receptors in the mouse medial habenula. Proceedings of the National Academy of Sciences of the United States of America. 123(36), e2536560123. mla: Önal, Cihan, et al. “Asymmetrical Modulation of Fear Expression via GABAB Receptors in the Mouse Medial Habenula.” Proceedings of the National Academy of Sciences of the United States of America, vol. 123, no. 36, e2536560123, National Academy of Sciences, 2026, doi:10.1073/pnas.2536560123. short: C. Önal, P. Koppensteiner, M.W. Muhia, E. Le Monnier, R. Shigemoto, Proceedings of the National Academy of Sciences of the United States of America 123 (2026). corr_author: '1' das_tickbox: '1' dataavailabilitystatement: All numerical data regarding electrophysiological recordings, calcium imaging, image analysis and behavioral tracking included in the article and/or SI Appendix have been deposited and are publicly available at ISTA REx (https://doi.org/10.15479/AT-ISTA-22704). date_created: 2026-09-13T22:01:52Z date_published: 2026-09-08T00:00:00Z date_updated: 2026-09-16T09:55:16Z day: '08' ddc: - '570' department: - _id: RySh - _id: PreCl doi: 10.1073/pnas.2536560123 ec_funded: 1 external_id: pmid: - '42673459' file: - access_level: open_access checksum: 8efe98c02ba79b9a3d76b7d6c1edbfbc content_type: application/pdf creator: dernst date_created: 2026-09-16T09:09:58Z date_updated: 2026-09-16T09:09:58Z file_id: '22936' file_name: 2026_PNAS_Oenal.pdf file_size: 7496942 relation: main_file success: 1 file_date_updated: 2026-09-16T09:09:58Z fulldoi: https://doi.org/10.1073/pnas.2536560123 has_accepted_license: '1' intvolume: ' 123' issue: '36' keyword: - medial habenula - GABAB receptor - asymmetry - fear conditioning - mouse language: - iso: eng license: https://creativecommons.org/licenses/by-nc-nd/4.0/ month: '09' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 92503f6e-16d5-11f0-9cad-8c571927f3b7 grant_number: PAT 5720324 name: New regime of presynaptic release regulation - _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 publication_status: published publisher: National Academy of Sciences quality_controlled: '1' related_material: record: - id: '22704' relation: research_data status: public researchdata_availability: yes scopus_import: '1' status: public supplementarymaterial: yes title: Asymmetrical modulation of fear expression via GABAB receptors in the mouse medial habenula 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: 123 year: '2026' ... --- OA_place: repository _id: '22704' abstract: - lang: eng text: "The medial habenula (MHb) is implicated in regulating emotional responses to aversive events. Studies in zebrafish have identified a remarkable morphological left–right asymmetry in the dorsal habenula (zebrafish equivalent of mammalian MHb)-interpeduncular nucleus (IPN) pathway and its asymmetrical roles in behavior. However, there is little evidence for structural or functional lateralization in the mammalian MHb-IPN pathway. Here, we investigated the synaptic properties of left- and right-MHb afferents to the IPN and their roles in the expression of conditioned fear in mice. We found that each IPN neuron receives inputs from both left and right MHb, but the left MHb-originating synapses exhibit lower release probability and higher γ-aminobutyric acid type B receptor (GABABR)-mediated potentiation compared to the right MHb-originating synapses. Interestingly, these asymmetrical properties persist in the inversus visceral mutant mice with normal internal organ laterality (situs solitus), but nearly disappear in those with reversed internal organ laterality (situs inversus). Behaviorally, chemogenetic inhibition of cholinergic neurons and conditional deletion of GABABR in the left, but not the right, MHb significantly attenuated cue-dependent fear recall. Our results demonstrate functional asymmetry of the MHb under partial influence of the nodal flow in mice, revealing a predominant role of GABABR-mediated signaling in the left MHb-IPN pathway in modulating fear memories. These findings suggest that lateralized MHb pathways could represent a fundamental principle in the neural regulation of emotion across species but that they develop differently in zebrafish and mice.\r\n" acknowledged_ssus: - _id: M-Shop - _id: PreCl article_processing_charge: No author: - first_name: Elodie full_name: Le Monnier, Elodie id: 3B59276A-F248-11E8-B48F-1D18A9856A87 last_name: Le Monnier - first_name: Cihan full_name: Önal, Cihan last_name: Önal citation: ama: Le Monnier E, Önal C. Asymmetrical modulation of fear expression via GABAB receptors in the mouse medial habenula. 2026. doi:10.15479/AT-ISTA-22704 apa: Le Monnier, E., & Önal, C. (2026). Asymmetrical modulation of fear expression via GABAB receptors in the mouse medial habenula. Institute of Science and Technology Austria. https://doi.org/10.15479/AT-ISTA-22704 chicago: Le Monnier, Elodie, and Cihan Önal. “Asymmetrical Modulation of Fear Expression via GABAB Receptors in the Mouse Medial Habenula.” Institute of Science and Technology Austria, 2026. https://doi.org/10.15479/AT-ISTA-22704. ieee: E. Le Monnier and C. Önal, “Asymmetrical modulation of fear expression via GABAB receptors in the mouse medial habenula.” Institute of Science and Technology Austria, 2026. ista: Le Monnier E, Önal C. 2026. Asymmetrical modulation of fear expression via GABAB receptors in the mouse medial habenula, Institute of Science and Technology Austria, 10.15479/AT-ISTA-22704. mla: Le Monnier, Elodie, and Cihan Önal. Asymmetrical Modulation of Fear Expression via GABAB Receptors in the Mouse Medial Habenula. Institute of Science and Technology Austria, 2026, doi:10.15479/AT-ISTA-22704. short: E. Le Monnier, C. Önal, (2026). corr_author: '1' date_created: 2026-08-13T12:20:08Z date_published: 2026-08-13T00:00:00Z date_updated: 2026-09-16T09:55:15Z day: '13' department: - _id: RySh doi: 10.15479/AT-ISTA-22704 doi_confirm: '1' ec_funded: 1 file: - access_level: open_access checksum: 7742bb211a43bb87c2b5ce7bda3068ae content_type: application/x-zip-compressed creator: elemonni date_created: 2026-08-13T12:07:53Z date_updated: 2026-08-13T12:07:53Z file_id: '22705' file_name: Behavior.zip file_size: 162086 relation: main_file success: 1 - access_level: open_access checksum: a162eb6103a770d94536374e02934fcf content_type: application/x-zip-compressed creator: elemonni date_created: 2026-08-13T12:07:57Z date_updated: 2026-08-13T12:07:57Z file_id: '22706' file_name: image_analysis.zip file_size: 6643 relation: main_file success: 1 - access_level: open_access checksum: 608aaf395bba5fd9cf62d8c8940d63aa content_type: application/x-zip-compressed creator: elemonni date_created: 2026-08-13T12:07:59Z date_updated: 2026-08-13T12:07:59Z file_id: '22707' file_name: Recordings.zip file_size: 1193016 relation: main_file success: 1 - access_level: open_access checksum: 2389ebd71238bd7de03d20504a8cf962 content_type: text/plain creator: elemonni date_created: 2026-08-13T13:06:29Z date_updated: 2026-08-13T13:06:29Z file_id: '22708' file_name: README.txt file_size: 246 relation: main_file success: 1 file_date_updated: 2026-08-13T13:06:29Z fulldoi: https://doi.org/10.15479/AT-ISTA-22704 has_accepted_license: '1' month: '08' oa: 1 oa_version: None project: - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program - _id: 92503f6e-16d5-11f0-9cad-8c571927f3b7 grant_number: PAT 5720324 name: New regime of presynaptic release regulation publisher: Institute of Science and Technology Austria related_material: record: - id: '22913' relation: used_in_publication status: public status: public title: Asymmetrical modulation of fear expression via GABAB receptors in the mouse medial habenula 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: research_data user_id: 68b8ca59-c5b3-11ee-8790-cd641c68093d year: '2026' ... --- DOAJ_listed: '1' OA_place: publisher OA_type: gold PlanS_conform: '1' _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. Cell Press. 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. Cell Press, 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. Cell Press, 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, Cell Press, 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). das_tickbox: '1' dataavailabilitystatement: "This study did not generate new materials or reagents.All data supporting the findings of this study are available from the lead contact upon reasonable request.\r\nThis study did not generate any new code.\r\nAdditional raw data can be obtained from the lead contact upon reasonable request." date_created: 2026-03-29T22:07:07Z date_published: 2026-04-17T00:00:00Z date_updated: 2026-10-20T09:02:33Z day: '17' ddc: - '570' department: - _id: RySh doi: 10.1016/j.isci.2026.115192 external_id: pmid: - '41890976' file: - access_level: open_access checksum: 9c9ccc87072d04808e4af407d647ed20 content_type: application/pdf creator: dernst date_created: 2026-07-27T12:03:23Z date_updated: 2026-07-27T12:03:23Z file_id: '22427' file_name: 2026_iScience_Akther.pdf file_size: 14469960 relation: main_file success: 1 file_date_updated: 2026-07-27T12:03:23Z fulldoi: https://doi.org/10.1016/j.isci.2026.115192 has_accepted_license: '1' intvolume: ' 29' issue: '4' language: - iso: eng month: '04' oa: 1 oa_version: Published Version pmid: 1 publication: iScience publication_identifier: eissn: - 2589-0042 publication_status: published publisher: Cell Press quality_controlled: '1' researchdata_availability: upon request scopus_import: '1' status: public supplementarymaterial: no title: Distribution and functional significance of rodent cerebellar glycogen 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: 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 fulldoi: https://doi.org/10.14670/HH-18-970 has_accepted_license: '1' intvolume: ' 40' issue: '12' language: - iso: eng 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). das_tickbox: '1' dataavailabilitystatement: All data used and/or analyzed during the current study are available from the corresponding author on reasonable request. date_created: 2024-07-22T07:48:20Z date_published: 2025-03-01T00:00:00Z date_updated: 2026-10-21T08:30:00Z 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 fulldoi: https://doi.org/10.1111/bpa.13279 has_accepted_license: '1' intvolume: ' 35' isi: 1 issue: '2' language: - iso: eng 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' researchdata_availability: upon request scopus_import: '1' status: public supplementarymaterial: yes 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: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 35 year: '2025' ... --- OA_place: publisher _id: '19271' abstract: - lang: eng text: "The medial habenula (MHb) is implicated in regulating emotional responses\r\nto aversive events. Studies in zebrafish have identified a remarkable morphological\r\nleft-right asymmetry in the dorsal habenula (zebrafish equivalent of mammalian\r\nMHb)-to-interpeduncular nucleus (IPN) pathway and its left-side specific role in\r\nmodulating fear responses. However, there is little evidence for structural or\r\nfunctional lateralization in the mammalian MHb-IPN pathway.\r\nHere, I investigated the synaptic properties of the left and right MHb\r\nafferents to the IPN in mice and addressed whether these synaptic connections\r\nselectively influence the expression of conditioned fear in mice. My findings reveal\r\nthat each individual IPN neuron receives inputs from both left and right MHb.\r\nElectrophysiological recordings from the same postsynaptic IPN neurons\r\ndemonstrate that the left MHb-originating synapses exhibit lower release\r\nprobability and higher \U0001D6FE-aminobutyric acid type B receptor (GABABR)-mediated\r\npotentiation compared to the right MHb-originating synapses. Interestingly,\r\nchemogenetic inhibition of cholinergic neurons in the left but not the right MHb\r\nsignificantly attenuated cue-dependent fear recall. Furthermore, conditional\r\ndeletion of GABABR in the left MHb interfered with the recall of cued fear memory,\r\nwhereas that in the right MHb neurons spared fear memory expression.\r\nCollectively, I demonstrate a functional asymmetry of the MHb in mice,\r\nrevealing a predominant role for GABABR-mediated signaling in the left MHb-IPN\r\npathway in the modulation of fear memories. These findings suggest that\r\nlateralized pathways could represent a fundamental principle in the neural\r\nregulation of emotion across species." acknowledged_ssus: - _id: PreCl - _id: M-Shop acknowledgement: "I would like to thank the European Research Council and European Commission, under the European Union’s Horizon 2020 research and innovation program (ERC grant agreement no. 694539 to Ryuichi Shigemoto and the Marie Skłodowska-Curie grant agreement no. 665385 to Cihan Önal), and the Austrian Neuroscience Association for providing financial support and opportunities, which were important in allowing me to present my work. I also wish to thank the\r\nPreclinical Facility, especially Michael Schunn, for always welcoming me from my earliest days as an intern. My gratitude goes as well to the Miba Machine Shop, in particular Todor Asenov, Astrit Arslani, and Thomas Menner, whose technical expertise often saved the day." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Hüseyin C full_name: Önal, Hüseyin C id: 4659D740-F248-11E8-B48F-1D18A9856A87 last_name: Önal orcid: 0000-0002-2771-2011 citation: ama: Önal C. Asymmetrical modulation of fear expression via GABAB receptors in the mouse medial habenula. 2025. doi:10.15479/AT-ISTA-19271 apa: Önal, C. (2025). Asymmetrical modulation of fear expression via GABAB receptors in the mouse medial habenula. Institute of Science and Technology Austria. https://doi.org/10.15479/AT-ISTA-19271 chicago: Önal, Cihan. “Asymmetrical Modulation of Fear Expression via GABAB Receptors in the Mouse Medial Habenula.” Institute of Science and Technology Austria, 2025. https://doi.org/10.15479/AT-ISTA-19271. ieee: C. Önal, “Asymmetrical modulation of fear expression via GABAB receptors in the mouse medial habenula,” Institute of Science and Technology Austria, 2025. ista: Önal C. 2025. Asymmetrical modulation of fear expression via GABAB receptors in the mouse medial habenula. Institute of Science and Technology Austria. mla: Önal, Cihan. Asymmetrical Modulation of Fear Expression via GABAB Receptors in the Mouse Medial Habenula. Institute of Science and Technology Austria, 2025, doi:10.15479/AT-ISTA-19271. short: C. Önal, Asymmetrical Modulation of Fear Expression via GABAB Receptors in the Mouse Medial Habenula, Institute of Science and Technology Austria, 2025. corr_author: '1' date_created: 2025-02-28T14:15:53Z date_published: 2025-03-04T00:00:00Z date_updated: 2026-10-21T08:33:44Z day: '04' ddc: - '570' - '571' - '573' - '599' degree_awarded: PhD department: - _id: GradSch - _id: RySh doi: 10.15479/AT-ISTA-19271 ec_funded: 1 file: - access_level: closed checksum: c1a4d75a7471de9f954697b06cd18d28 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: hoenal date_created: 2025-02-28T13:57:01Z date_updated: 2026-02-01T23:30:02Z embargo_to: open_access file_id: '19272' file_name: Cihan_Onal_Thesis_Final.docx file_size: 25869143 relation: source_file - access_level: open_access checksum: de4e62147ab9f04098dc8cd898c630da content_type: application/pdf creator: hoenal date_created: 2025-02-28T13:57:04Z date_updated: 2026-02-01T23:30:02Z embargo: 2026-02-01 file_id: '19273' file_name: Cihan_Onal_Thesis_Final_pdfa.pdf file_size: 12077596 relation: main_file file_date_updated: 2026-02-01T23:30:02Z fulldoi: https://doi.org/10.15479/AT-ISTA-19271 has_accepted_license: '1' language: - iso: eng license: https://creativecommons.org/licenses/by-nc/4.0/ month: '03' oa: 1 oa_version: Published Version 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_identifier: eissn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '9437' relation: part_of_dissertation status: public - id: '15084' relation: part_of_dissertation status: public status: public supervisor: - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 title: Asymmetrical modulation of fear expression via GABAB receptors in the mouse medial habenula 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: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2025' ... --- 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 fulldoi: https://doi.org/10.1371/journal.pbio.3002879 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' ... --- _id: '18296' 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 murine 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. article_processing_charge: No author: - first_name: Olena full_name: Kim, Olena id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87 last_name: Kim orcid: 0000-0003-2344-1039 citation: ama: Kim O. Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. 2024. doi:10.15479/AT:ISTA:18296 apa: Kim, O. (2024). Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:18296 chicago: Kim, Olena. “Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber Boutons.” Institute of Science and Technology Austria, 2024. https://doi.org/10.15479/AT:ISTA:18296. ieee: O. Kim, “Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons.” Institute of Science and Technology Austria, 2024. ista: Kim O. 2024. Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons, Institute of Science and Technology Austria, 10.15479/AT:ISTA:18296. mla: Kim, Olena. Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber Boutons. Institute of Science and Technology Austria, 2024, doi:10.15479/AT:ISTA:18296. short: O. Kim, (2024). contributor: - contributor_type: researcher first_name: Olena id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87 last_name: Kim - contributor_type: researcher first_name: Yuji id: 3337E116-F248-11E8-B48F-1D18A9856A87 last_name: Okamoto orcid: 0000-0003-0408-6094 - contributor_type: researcher first_name: Walter id: 3F99E422-F248-11E8-B48F-1D18A9856A87 last_name: Kaufmann orcid: 0000-0001-9735-5315 - contributor_type: researcher first_name: 'Nils ' last_name: Brose - contributor_type: researcher first_name: Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - contributor_type: supervisor first_name: Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 corr_author: '1' date_created: 2024-10-11T10:12:17Z date_published: 2024-10-11T00:00:00Z date_updated: 2026-09-14T08:48:01Z day: '11' ddc: - '570' department: - _id: PeJo - _id: RySh - _id: EM-Fac doi: 10.15479/AT:ISTA:18296 ec_funded: 1 file: - access_level: open_access checksum: 0a977e7df54c418251b10dfd3f8a015c content_type: application/zip creator: okim date_created: 2024-10-11T10:04:19Z date_updated: 2024-10-11T10:04:19Z file_id: '18297' file_name: Kim_et_al_2024_PlosBio_Source_data.zip file_size: 164382 relation: main_file success: 1 - access_level: open_access checksum: 5b9343d6b2035ac3185e390fad4d3830 content_type: text/plain creator: okim date_created: 2024-10-11T10:04:23Z date_updated: 2024-10-11T10:04:23Z file_id: '18298' file_name: info.txt file_size: 654 relation: main_file success: 1 file_date_updated: 2024-10-11T10:04:23Z fulldoi: https://doi.org/10.15479/AT:ISTA:18296 has_accepted_license: '1' keyword: - Hippocampal mossy fiber synapses - short-term potentiation - long-term potentiation - presynaptic plasticity - electron microscopy - freeze-fracture replica labeling - paired recordings - forskolin - cyclic adenosine monophosphate (cAMP) - protein kinase A (PKA) - neuromodulation - synaptic vesicle pools - presynaptic Ca2+ channels - Munc13 - docking - priming - active zone month: '10' oa: 1 oa_version: Submitted Version project: - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glutamatergic synapse publisher: Institute of Science and Technology Austria related_material: record: - id: '18603' relation: used_in_publication status: public 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: research_data user_id: 68b8ca59-c5b3-11ee-8790-cd641c68093d 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 & 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 & 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 & 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 & 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 & 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 & 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 & Neuroinflammation 11 (2024) e200284. das_tickbox: '1' dataavailabilitystatement: Data that support the findings of this study are available from the corresponding author on reasonable request. date_created: 2024-08-25T22:01:07Z date_published: 2024-09-01T00:00:00Z date_updated: 2026-09-17T11:27:41Z 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 fulldoi: https://doi.org/10.1212/NXI.0000000000200284 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 & 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 researchdata_availability: upon request scopus_import: '1' status: public supplementarymaterial: yes 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: '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' das_tickbox: '0' date_created: 2024-09-10T12:32:38Z date_published: 2024-08-27T00:00:00Z date_updated: 2026-10-01T11:17:28Z 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 fulldoi: https://doi.org/10.1007/978-1-0716-4019-7_8 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' researchdata_availability: no scopus_import: '1' status: public supplementarymaterial: no title: Automated Imaging and Analysis of Synapses in Freeze-Fracture Replica Samples with Deep Learning type: book_chapter user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345 year: '2024' ... --- DOAJ_listed: '1' OA_place: publisher OA_type: gold PlanS_conform: '1' _id: '18445' abstract: - lang: eng text: Acquisition of specialized cellular features is controlled by the ordered expression of transcription factors (TFs) along differentiation trajectories. Here, we find a member of the Onecut TF family, ONECUT3, expressed in postmitotic neurons that leave their Ascl1+/Onecut1/2+ proliferative domain in the vertebrate hypothalamus to instruct neuronal differentiation. We combined single-cell RNA-seq and gain-of-function experiments for gene network reconstruction to show that ONECUT3 affects the polarization and morphogenesis of both hypothalamic GABA-derived dopamine and thyrotropin-releasing hormone (TRH)+ glutamate neurons through neuron navigator-2 (NAV2). In vivo, siRNA-mediated knockdown of ONECUT3 in neonatal mice reduced NAV2 mRNA, as well as neurite complexity in Onecut3-containing neurons, while genetic deletion of Onecut3/ceh-48 in C. elegans impaired neurocircuit wiring, and sensory discrimination-based behaviors. Thus, ONECUT3, conserved across neuronal subtypes and many species, underpins the polarization and morphological plasticity of phenotypically distinct neurons that descend from a common pool of Ascl1+ progenitors in the hypothalamus. acknowledgement: "The authors thank Z. Máté, G. Szabó, and F. Erdélyi for the custom generation of transgenic mouse lines, C. Fekete for Trh transgenic tissues (all from the Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary), A. Goudmaeker for IVF recovery of a frozen mouse line (SSS animal facility, Université catholique de Louvain), and Y. Yanagawa (Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi, Japan) for providing GAD67gfp/+ mice. We also thank S. Cloer, D. Preininger, and A. Weissenbacher (Tiergarten Schönbrunn, Vienna, Austria) for providing naked mole rats, Seba’s fruit bats, and Indian flying foxes, as well as F. Aujard (CNRS, UMR 7179 ‘Adaptive mechanisms and evolution’, France) for Microcebus tissues. I. Milenkovic and G.G. Kovács (Clinical Institute of Neurology, Medical University of Vienna, Vienna, Austria) are acknowledged for providing post-mortem human brain samples. We are indebted to S. Rehman (Medical University of Vienna), M. Kalusa (University of Leipzig, Leipzig, Germany), and W. Reimann (Paul Flechsig Institute for Brain Research, Leipzig, Germany) for their technical assistance. C. elegans strains were provided by the National Bioresource Project for the nematode, Japan, and the CGC, with the latter being funded by the NIH Office of Research Infrastructure Programs (P40 OD010440). This work was supported by the Austrian Science Fund (FWF, P 34121-B; to E.K.), the Swedish Research Council (2023-03058, T.Ha; 2020-01688, T.Hö.), the Swedish Brain Foundation (Hjärnfonden, FO2022-0300, to T.Ha.), the Novo Nordisk Foundation (NNF23OC0084476, to T.Ha.), the European Research Council (FOODFORLIFE, ERC-2020-AdG-101021016; to T.Ha.), the Université Catholique de Louvain (‘Fonds spéciaux de recherche’-FSR, to F.C.), and Fonds de la Recherche Scientifique F.R.S.-FNRS (‘Project de recherche (PDR)’ #T.0039.21, to F.C.). S.J.E. is supported by the Simons Foundation #543069. I.L. is supported by a post-doctoral fellowship from the Human Frontiers Science Program (LT000335/2020-L). E.R. holds a PhD grant from the FRIA (F.R.S.-FNRS, Belgium). F.C. is a Research Director of the F.R.S.-FNRS (Belgium).\r\nOpen access funding provided by Karolinska Institute." article_number: '8631' article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Maja full_name: Zupančič, Maja last_name: Zupančič - first_name: Erik full_name: Keimpema, Erik last_name: Keimpema - first_name: Evgenii O. full_name: Tretiakov, Evgenii O. last_name: Tretiakov - first_name: Stephanie J. full_name: Eder, Stephanie J. last_name: Eder - first_name: Itamar full_name: Lev, Itamar last_name: Lev - first_name: Lukas full_name: Englmaier, Lukas last_name: Englmaier - first_name: Pradeep full_name: Bhandari, Pradeep id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87 last_name: Bhandari orcid: 0000-0003-0863-4481 - first_name: Simone A. full_name: Fietz, Simone A. last_name: Fietz - first_name: Wolfgang full_name: Härtig, Wolfgang last_name: Härtig - first_name: Estelle full_name: Renaux, Estelle last_name: Renaux - first_name: Andreas full_name: Villunger, Andreas last_name: Villunger - first_name: Tomas full_name: Hökfelt, Tomas last_name: Hökfelt - first_name: Manuel full_name: Zimmer, Manuel last_name: Zimmer - first_name: Frédéric full_name: Clotman, Frédéric last_name: Clotman - first_name: Tibor full_name: Harkany, Tibor last_name: Harkany citation: ama: Zupančič M, Keimpema E, Tretiakov EO, et al. Concerted transcriptional regulation of the morphogenesis of hypothalamic neurons by ONECUT3. Nature Communications. 2024;15. doi:10.1038/s41467-024-52762-z apa: Zupančič, M., Keimpema, E., Tretiakov, E. O., Eder, S. J., Lev, I., Englmaier, L., … Harkany, T. (2024). Concerted transcriptional regulation of the morphogenesis of hypothalamic neurons by ONECUT3. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-024-52762-z chicago: Zupančič, Maja, Erik Keimpema, Evgenii O. Tretiakov, Stephanie J. Eder, Itamar Lev, Lukas Englmaier, Pradeep Bhandari, et al. “Concerted Transcriptional Regulation of the Morphogenesis of Hypothalamic Neurons by ONECUT3.” Nature Communications. Springer Nature, 2024. https://doi.org/10.1038/s41467-024-52762-z. ieee: M. Zupančič et al., “Concerted transcriptional regulation of the morphogenesis of hypothalamic neurons by ONECUT3,” Nature Communications, vol. 15. Springer Nature, 2024. ista: Zupančič M, Keimpema E, Tretiakov EO, Eder SJ, Lev I, Englmaier L, Bhandari P, Fietz SA, Härtig W, Renaux E, Villunger A, Hökfelt T, Zimmer M, Clotman F, Harkany T. 2024. Concerted transcriptional regulation of the morphogenesis of hypothalamic neurons by ONECUT3. Nature Communications. 15, 8631. mla: Zupančič, Maja, et al. “Concerted Transcriptional Regulation of the Morphogenesis of Hypothalamic Neurons by ONECUT3.” Nature Communications, vol. 15, 8631, Springer Nature, 2024, doi:10.1038/s41467-024-52762-z. short: M. Zupančič, E. Keimpema, E.O. Tretiakov, S.J. Eder, I. Lev, L. Englmaier, P. Bhandari, S.A. Fietz, W. Härtig, E. Renaux, A. Villunger, T. Hökfelt, M. Zimmer, F. Clotman, T. Harkany, Nature Communications 15 (2024). das_tickbox: '1' dataavailabilitystatement: The snRNA-seq data generated in this study have been deposited in the NCBI Gene Expression Omnibus database under accession code GSE132730 and as ‘Supplementary Data 1 - Neuro2a-onecut3-overexpression’. All other primary data were made publically available at https://github.com/Harkany-Lab/Zupancic_2023 and deposited to Figshare.com with https://doi.org/10.6084/m9.figshare.22680433. Source data are provided with this paper. date_created: 2024-10-20T22:02:05Z date_published: 2024-10-05T00:00:00Z date_updated: 2026-10-01T12:17:25Z day: '05' ddc: - '570' department: - _id: RySh doi: 10.1038/s41467-024-52762-z external_id: isi: - '001409493300014' pmid: - '39366958' file: - access_level: open_access checksum: 03d6dd1b84efa24e9e9ede748d08764d content_type: application/pdf creator: dernst date_created: 2024-10-21T12:15:38Z date_updated: 2024-10-21T12:15:38Z file_id: '18460' file_name: 2024_NatureComm_Zupancic.pdf file_size: 7215329 relation: main_file success: 1 file_date_updated: 2024-10-21T12:15:38Z fulldoi: https://doi.org/10.1038/s41467-024-52762-z has_accepted_license: '1' intvolume: ' 15' isi: 1 language: - iso: eng month: '10' 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' related_material: record: - id: '22961' relation: research_data status: public researchdata_availability: yes scopus_import: '1' status: public supplementarymaterial: yes title: Concerted transcriptional regulation of the morphogenesis of hypothalamic neurons by ONECUT3 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: 15 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' das_tickbox: '1' dataavailabilitystatement: 'The mass spectrometry proteomics data have been deposited at the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifier PXD051022. The data used in the analysis can be found in the ISTA data repository DOI: 10.15479/AT:ISTA:15385. The code used to generate the results is available at: https://zenodo.org/records/11130588.' date_created: 2024-06-16T22:01:05Z date_published: 2024-06-10T00:00:00Z date_updated: 2026-10-21T08:31:42Z 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 fulldoi: https://doi.org/10.1371/journal.pbio.3002668 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 researchdata_availability: yes scopus_import: '1' status: public supplementarymaterial: yes 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' ... --- _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: 2026-10-21T08:31:42Z 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 fulldoi: https://doi.org/10.15479/AT:ISTA:15385 has_accepted_license: '1' keyword: - ASD - periaqueductal gray - perception - behavior - potassium channels 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' ... --- OA_place: publisher OA_type: hybrid _id: '14257' abstract: - lang: eng text: Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease. acknowledged_ssus: - _id: ScienComp - _id: Bio - _id: PreCl - _id: LifeSc - _id: M-Shop - _id: E-Lib acknowledgement: 'We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I. Erber for technical assistance; and M. Tomschik for support with obtaining human samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata for computational support and hardware control. We are grateful to R. Shigemoto and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University) for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly provided by S. Grant (University of Edinburgh). We acknowledge expert support by Institute of Science and Technology Austria’s scientific computing, imaging and optics, preclinical and lab support facilities and by the Miba machine shop and library. We gratefully acknowledge funding by the following sources: Austrian Science Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232 (J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award (P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27 (R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 692692 – GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).' article_processing_charge: Yes (in subscription journal) article_type: original author: - first_name: Julia M full_name: Michalska, Julia M id: 443DB6DE-F248-11E8-B48F-1D18A9856A87 last_name: Michalska orcid: 0000-0003-3862-1235 - first_name: Julia full_name: Lyudchik, Julia id: 46E28B80-F248-11E8-B48F-1D18A9856A87 last_name: Lyudchik - first_name: Philipp full_name: Velicky, Philipp id: 39BDC62C-F248-11E8-B48F-1D18A9856A87 last_name: Velicky orcid: 0000-0002-2340-7431 - first_name: Hana full_name: Korinkova, Hana id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed last_name: Korinkova - first_name: Jake full_name: Watson, Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Alban full_name: Cenameri, Alban id: 9ac8f577-2357-11eb-997a-e566c5550886 last_name: Cenameri - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Nicole full_name: Amberg, Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Alessandro full_name: Venturino, Alessandro id: 41CB84B2-F248-11E8-B48F-1D18A9856A87 last_name: Venturino orcid: 0000-0003-2356-9403 - first_name: Karl full_name: Roessler, Karl last_name: Roessler - first_name: Thomas full_name: Czech, Thomas last_name: Czech - first_name: Romana full_name: Höftberger, Romana last_name: Höftberger - first_name: Sandra full_name: Siegert, Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - 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: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 citation: ama: Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. 2024;42:1051-1064. doi:10.1038/s41587-023-01911-8 apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (2024). Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. Springer Nature. https://doi.org/10.1038/s41587-023-01911-8 chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Nature Biotechnology. Springer Nature, 2024. https://doi.org/10.1038/s41587-023-01911-8. ieee: J. M. Michalska et al., “Imaging brain tissue architecture across millimeter to nanometer scales,” Nature Biotechnology, vol. 42. Springer Nature, pp. 1051–1064, 2024. ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino G, Jonas PM, Danzl JG. 2024. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. 42, 1051–1064. mla: Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Nature Biotechnology, vol. 42, Springer Nature, 2024, pp. 1051–64, doi:10.1038/s41587-023-01911-8. short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology 42 (2024) 1051–1064. corr_author: '1' das_tickbox: '1' date_created: 2023-09-03T22:01:15Z date_published: 2024-07-01T00:00:00Z date_updated: 2026-10-21T08:36:20Z day: '01' ddc: - '570' department: - _id: SaSi - _id: GaNo - _id: PeJo - _id: JoDa - _id: Bio - _id: RySh doi: 10.1038/s41587-023-01911-8 ec_funded: 1 external_id: isi: - '001065254200001' pmid: - '37653226' file: - access_level: open_access checksum: 57d5fafb16f02dcb9f7dddb1bd7e2a71 content_type: application/pdf creator: dernst date_created: 2025-01-09T07:48:01Z date_updated: 2025-01-09T07:48:01Z file_id: '18784' file_name: 2024_NatureBiotech_Michalska.pdf file_size: 26065165 relation: main_file success: 1 file_date_updated: 2025-01-09T07:48:01Z fulldoi: https://doi.org/10.1038/s41587-023-01911-8 has_accepted_license: '1' intvolume: ' 42' isi: 1 language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: 1051-1064 pmid: 1 project: - _id: 265CB4D0-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03600 name: Optical control of synaptic function via adhesion molecules - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232 name: Molecular Drug Targets - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: Synaptic communication in neuronal microcircuits - _id: 23889792-32DE-11EA-91FC-C7463DDC885E grant_number: LS18-022 name: High content imaging to decode human immune cell interactions in health and allergic disease - _id: 25444568-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715508' name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glutamatergic synapse - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program - _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9 call_identifier: H2020 grant_number: '101026635' name: Synaptic computations of the hippocampal CA3 circuitry publication: Nature Biotechnology publication_identifier: eissn: - 1546-1696 issn: - 1087-0156 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - relation: software url: https://github.com/danzllab/CATS record: - id: '18660' relation: dissertation_contains status: deleted - id: '13126' relation: research_data status: public - id: '18674' relation: dissertation_contains status: public researchdata_availability: yes scopus_import: '1' status: public supplementarymaterial: yes title: Imaging brain tissue architecture across millimeter to nanometer scales 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: 42 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). das_tickbox: '1' dataavailabilitystatement: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. date_created: 2024-07-21T22:01:01Z date_published: 2024-07-12T00:00:00Z date_updated: 2026-10-21T08:35:21Z 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 fulldoi: https://doi.org/10.1126/sciadv.adk5462 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' researchdata_availability: yes (supplementary data) scopus_import: '1' status: public supplementarymaterial: yes 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' ... --- _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' das_tickbox: '1' dataavailabilitystatement: All data generated and analyzed in this study are included in the paper and/or supplementary materials. Raw sequencing data has been deposited at Gene Expression Omnibus (GEO). All scripts that were used to prepare data and figures for this manuscript are available via GitHub at https://github.com/fpauler. Accession numbers and github DOI are listed in the key resources table. Files for 3D printing of acute slice recovery chamber (3D model 361319) are deposited to https://www.printables.com. date_created: 2023-04-27T09:41:48Z date_published: 2024-01-17T00:00:00Z date_updated: 2026-10-21T09:51:58Z 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 fulldoi: https://doi.org/10.1016/j.neuron.2023.11.009 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/ researchdata_availability: yes scopus_import: '1' status: public supplementarymaterial: yes 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: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 112 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: 2026-10-22T22:31:22Z 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 fulldoi: https://doi.org/10.1016/j.neuron.2023.12.002 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' ... --- 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' das_tickbox: '1' date_created: 2024-03-05T09:23:55Z date_published: 2024-02-20T00:00:00Z date_updated: 2026-10-22T22:31:33Z 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 fulldoi: https://doi.org/10.1073/pnas.2301449121 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 researchdata_availability: yes scopus_import: '1' status: public supplementarymaterial: yes 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' ... --- _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 fulldoi: https://doi.org/10.1523/JNEUROSCI.1514-22.2023 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' ...