[{"_id":"22295","publisher":"Springer Nature","acknowledgement":"We thank F. Freeman, V. Voronin and M. Ladron de Guevara for technical assistance; A. Stichelberger and S. Liegenfeld for the management of our animal colony; M. Schunn, C. Gold and the Preclinical Facility team for technical assistance; C. Jansen and the Scientific Computing Facility for bioinformatics support and technical assistance; the Biomedical Sequencing Facility at CeMM for assistance with next-generation sequencing; and J. Lin and T. Krausgruber in the laboratory of C. Bock for support with flow cytometry; J. Kirchner for illustrating the multi-omics approach depicted in Fig. 1; and all members of the laboratory of G.N. for their support and discussions. This study was supported by the Scientific Service Units of ISTA through resources provided by the Imaging & Optics Facility and the Laboratory Support Facility. Bulk RNA-seq was performed by the Next Generation Sequencing Facility at Vienna BioCenter Core Facilities, member of the Vienna BioCenter. This work was supported by a European Research Council Consolidator Grant (PR1028ERC02), by SFARI (PR1028SIM02) and by the Austrian Science Fund (PE1028W1232 and PR1028FG1803) to G.N. Open access funding provided by Institute of Science and Technology (IST Austria).","related_material":{"link":[{"description":"News on ISTA website","relation":"press_release","url":"https://ista.ac.at/en/news/patterns-in-genetic-chaos/"}]},"doi":"10.1038/s41586-026-10679-1","year":"2026","day":"17","title":"Cortical development dynamics across autism spectrum disorder mouse models","PlanS_conform":"1","corr_author":"1","month":"06","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","article_type":"original","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"quality_controlled":"1","publication_identifier":{"eissn":["1476-4687"],"issn":["0028-0836"]},"supplementarymaterial":"yes","fulldoi":"https://doi.org/10.1038/s41586-026-10679-1","date_updated":"2026-08-04T09:29:55Z","researchdata_availability":"yes","oa_version":"Published Version","has_accepted_license":"1","scopus_import":"1","ddc":["570"],"publication":"Nature","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"status":"public","department":[{"_id":"AnKi"},{"_id":"GaNo"},{"_id":"TiVo"},{"_id":"ScienComp"},{"_id":"GradSch"},{"_id":"Bio"},{"_id":"PreCl"}],"date_published":"2026-06-17T00:00:00Z","abstract":[{"lang":"eng","text":"Despite the functional diversity of over 100 causal genes1,2,3, phenotypic convergence across models may reveal common neurobiological processes in autism spectrum disorder (ASD). Here we profiled 251 samples from 11 monogenic mouse models of ASD using single-nucleus multi-omic sequencing across three developmental stages, both sexes and two brain regions. Despite genetic heterogeneity, ASD-linked mutations converged on perturbations of the radial glial cell lineage. These alterations reflect a transient developmental delay rather than lasting lineage misspecification and resolve by postnatal stages. Molecularly, the largest transcriptional differences emerged in neurons at early postnatal stages. These changes included downregulation of synaptic and ion channel-related genes, consistent with homeostatic adaptation or delayed maturation. Network analysis showed molecular convergence across models within each developmental stage, suggesting that diverse mutations linked to ASD impinge on common, stage-specific processes. Convergence becomes less pronounced by postnatal day 14, highlighting the dynamic nature of ASD-associated changes. Cross-genotype heterogeneity is superimposed on stage-specific effects. Electrophysiology corroborated this pattern: mutants generally showed altered neuronal excitability and synaptic properties with model-specific nuances. Our study also highlighted sex-specific gene expression alterations, with female mice often displaying larger effect sizes than male mice. Together, our findings provide a comprehensive view of developmental cellular and molecular dynamics across models of ASD."}],"article_processing_charge":"Yes (via OA deal)","oa":1,"language":[{"iso":"eng"}],"external_id":{"pmid":["42310454"]},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1038/s41586-026-10679-1"}],"pmid":1,"OA_place":"publisher","date_created":"2026-07-13T09:47:21Z","author":[{"full_name":"Schwarz, Lena A","first_name":"Lena A","last_name":"Schwarz","id":"29A8453C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Christoph","full_name":"Dotter, Christoph","orcid":"0000-0002-9033-9096","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","last_name":"Dotter"},{"full_name":"Isaev, Sergey","first_name":"Sergey","last_name":"Isaev"},{"last_name":"Lisi","id":"39383c1b-d3eb-11ef-8d6c-c8cdf4e10c8c","full_name":"Lisi, Michela","first_name":"Michela"},{"first_name":"Daniel","full_name":"Malzl, Daniel","last_name":"Malzl"},{"id":"2a8c054c-0913-11ee-9159-f8ef515809ed","last_name":"Büschl","first_name":"Christoph","full_name":"Büschl, Christoph"},{"last_name":"Ladstätter","first_name":"Sabrina","full_name":"Ladstätter, Sabrina"},{"last_name":"Oliveira","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","full_name":"Oliveira, Bárbara","first_name":"Bárbara"},{"full_name":"Barel, Matteo","first_name":"Matteo","last_name":"Barel","id":"8959927b-2236-11ed-bd6e-ea83d94ade0e"},{"orcid":"0000-0003-1843-3173","full_name":"Basilico, Bernadette","first_name":"Bernadette","last_name":"Basilico","id":"36035796-5ACA-11E9-A75E-7AF2E5697425"},{"full_name":"Chintaluri, Chaitanya","orcid":"0000-0003-4252-1608","first_name":"Chaitanya","last_name":"Chintaluri","id":"BA06AFEE-A4BA-11EA-AE5C-14673DDC885E"},{"first_name":"Sarah","full_name":"Gorkiewicz, Sarah","id":"f141a35d-15a9-11ec-9fb2-fef6becc7b6f","last_name":"Gorkiewicz"},{"id":"3384113A-F248-11E8-B48F-1D18A9856A87","last_name":"Goudarzi","first_name":"Mohammad","full_name":"Goudarzi, Mohammad"},{"last_name":"Belinova","id":"0bf89b6a-d28b-11eb-8bd6-f43768e4d368","full_name":"Belinova, Tereza","first_name":"Tereza"},{"last_name":"Reichl","full_name":"Reichl, Stephan","first_name":"Stephan"},{"first_name":"Gintarė","full_name":"Sendžikaitė, Gintarė","id":"dd6d52f2-c50d-11eb-9548-bcf0ff82b344","last_name":"Sendžikaitė"},{"first_name":"Satish","full_name":"Arcot Jayaram, Satish","orcid":"0000-0002-2479-2669","id":"b0bbee33-09f7-11eb-909c-8b358058d28a","last_name":"Arcot Jayaram"},{"first_name":"Peter","orcid":"0000-0002-3509-1948","full_name":"Koppensteiner, Peter","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","last_name":"Koppensteiner"},{"last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","first_name":"Christoph M"},{"first_name":"Tim P","orcid":"0000-0003-3295-6181","full_name":"Vogels, Tim P","id":"CB6FF8D2-008F-11EA-8E08-2637E6697425","last_name":"Vogels"},{"first_name":"Jörg","full_name":"Menche, Jörg","last_name":"Menche"},{"first_name":"Igor","full_name":"Adameyko, Igor","last_name":"Adameyko"},{"last_name":"Kharchenko","id":"0095641e-7eb7-11f1-8665-aec51a2ab5e0","full_name":"Kharchenko, Peter Vasili","first_name":"Peter Vasili"},{"last_name":"Bock","full_name":"Bock, Christoph","first_name":"Christoph"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178"}],"OA_type":"hybrid","type":"journal_article","project":[{"grant_number":"101044865","_id":"34ba8964-11ca-11ed-8bc3-e15864e7e9a6","name":"Toward an understanding of the brain interstitial system and the extracellular proteome in health and autism spectrum disorders"},{"_id":"9B91375C-BA93-11EA-9121-9846C619BF3A","grant_number":"707964","name":"Critical windows and reversibility of ASD associated with mutations in chromatin remodelers"},{"grant_number":"W1232","_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Drug Targets"},{"name":"Neurobiology of anxiety in autism spectrum disorders","grant_number":"FG1803 49015","_id":"ebb38b5d-77a9-11ec-83b8-a42e08120a88"}],"publication_status":"epub_ahead","dataavailabilitystatement":"Single-nucleus multiomics data are available from the Gene Expression Omnibus (GSE328363). The mm10 reference genome was used for the alignment (refdata-cellranger-arc-mm10-2020-A-2.0.0, obtained from https://cf.10xgenomics.com/supp/cell-arc/refdata-cellranger-arc-mm10-2020-A-2.0.0.tar.gz). Single-cell data can be accessed and visualized through a CELLxGENE database (https://adameykolab.hifo.meduniwien.ac.at/cellxgene_public/filecrawl/.2026_Nature_Schwarz). Source data are provided with this paper. Scripts and analyses that support the main findings of this study are accessible in a GitHub repository (https://git.ista.ac.at/research-sofware/mouseome).","citation":{"ieee":"L. A. Schwarz <i>et al.</i>, “Cortical development dynamics across autism spectrum disorder mouse models,” <i>Nature</i>. Springer Nature, 2026.","chicago":"Schwarz, Lena A, Christoph Dotter, Sergey Isaev, Michela Lisi, Daniel Malzl, Christoph Büschl, Sabrina Ladstätter, et al. “Cortical Development Dynamics across Autism Spectrum Disorder Mouse Models.” <i>Nature</i>. Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s41586-026-10679-1\">https://doi.org/10.1038/s41586-026-10679-1</a>.","ama":"Schwarz LA, Dotter C, Isaev S, et al. Cortical development dynamics across autism spectrum disorder mouse models. <i>Nature</i>. 2026. doi:<a href=\"https://doi.org/10.1038/s41586-026-10679-1\">10.1038/s41586-026-10679-1</a>","mla":"Schwarz, Lena A., et al. “Cortical Development Dynamics across Autism Spectrum Disorder Mouse Models.” <i>Nature</i>, Springer Nature, 2026, doi:<a href=\"https://doi.org/10.1038/s41586-026-10679-1\">10.1038/s41586-026-10679-1</a>.","ista":"Schwarz LA, Dotter C, Isaev S, Lisi M, Malzl D, Büschl C, Ladstätter S, Oliveira B, Barel M, Basilico B, Chintaluri C, Gorkiewicz S, Goudarzi M, Belinova T, Reichl S, Sendžikaitė G, Arcot Jayaram S, Koppensteiner P, Sommer CM, Vogels TP, Menche J, Adameyko I, Kharchenko PV, Bock C, Novarino G. 2026. Cortical development dynamics across autism spectrum disorder mouse models. Nature.","apa":"Schwarz, L. A., Dotter, C., Isaev, S., Lisi, M., Malzl, D., Büschl, C., … Novarino, G. (2026). Cortical development dynamics across autism spectrum disorder mouse models. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-026-10679-1\">https://doi.org/10.1038/s41586-026-10679-1</a>","short":"L.A. Schwarz, C. Dotter, S. Isaev, M. Lisi, D. Malzl, C. Büschl, S. Ladstätter, B. Oliveira, M. Barel, B. Basilico, C. Chintaluri, S. Gorkiewicz, M. Goudarzi, T. Belinova, S. Reichl, G. Sendžikaitė, S. Arcot Jayaram, P. Koppensteiner, C.M. Sommer, T.P. Vogels, J. Menche, I. Adameyko, P.V. Kharchenko, C. Bock, G. Novarino, Nature (2026)."}},{"isi":1,"oa_version":"Published Version","date_updated":"2026-06-18T18:12:08Z","volume":28,"fulldoi":"https://doi.org/10.1038/s41593-025-01874-w","quality_controlled":"1","publication_identifier":{"issn":["1097-6256"],"eissn":["1546-1726"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"article_type":"original","month":"03","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics","corr_author":"1","year":"2025","day":"01","related_material":{"record":[{"status":"public","relation":"research_data","id":"18579"}],"link":[{"description":"News on ISTA Website","relation":"press_release","url":"https://ista.ac.at/en/news/high-tech-video-optimization-in-our-brain/"}]},"_id":"19076","publisher":"Springer Nature","acknowledgement":"We thank Y. Ben-Simon for generously making viral vectors for retrograde tracing available, as well as J. Watson and F. Marr for reagents. We also thank R. Shigemoto, W. Młynarski and members of the Neuroethology group for their comments on the manuscript and L. Burnett for her schematic drawings. This research was supported by the Scientific Service Units of ISTA through resources provided by Scientific Computing, the Preclinical Facility, the Lab Support Facility and the Imaging and Optics Facility, in particular F. Lange, M. Schunn and T. Asenov. This work was supported by European Research Council Starting Grant no. 756502 (M.J.) and European Research Council Consolidator Grant no. 101086580 (M.J.); and EMBO ALTF grant no. 1098-2017 (A.S.) and Human Frontiers Science Program grant no. LT000256/2018-L (A.S.). Open access funding provided by Institute of Science and Technology (IST Austria).","doi":"10.1038/s41593-025-01874-w","citation":{"short":"T.A. Vega Zuniga, A.L. Sumser, O. Symonova, P. Koppensteiner, F. Schmidt, M.A. Jösch, Nature Neuroscience 28 (2025).","apa":"Vega Zuniga, T. A., Sumser, A. L., Symonova, O., Koppensteiner, P., Schmidt, F., &#38; Jösch, M. A. (2025). A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics. <i>Nature Neuroscience</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41593-025-01874-w\">https://doi.org/10.1038/s41593-025-01874-w</a>","ista":"Vega Zuniga TA, Sumser AL, Symonova O, Koppensteiner P, Schmidt F, Jösch MA. 2025. A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics. Nature Neuroscience. 28, 7278.","chicago":"Vega Zuniga, Tomas A, Anton L Sumser, Olga Symonova, Peter Koppensteiner, Florian Schmidt, and Maximilian A Jösch. “A Thalamic Hub-and-Spoke Network Enables Visual Perception during Action by Coordinating Visuomotor Dynamics.” <i>Nature Neuroscience</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1038/s41593-025-01874-w\">https://doi.org/10.1038/s41593-025-01874-w</a>.","ieee":"T. A. Vega Zuniga, A. L. Sumser, O. Symonova, P. Koppensteiner, F. Schmidt, and M. A. Jösch, “A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics,” <i>Nature Neuroscience</i>, vol. 28. Springer Nature, 2025.","ama":"Vega Zuniga TA, Sumser AL, Symonova O, Koppensteiner P, Schmidt F, Jösch MA. A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics. <i>Nature Neuroscience</i>. 2025;28. doi:<a href=\"https://doi.org/10.1038/s41593-025-01874-w\">10.1038/s41593-025-01874-w</a>","mla":"Vega Zuniga, Tomas A., et al. “A Thalamic Hub-and-Spoke Network Enables Visual Perception during Action by Coordinating Visuomotor Dynamics.” <i>Nature Neuroscience</i>, vol. 28, 7278, Springer Nature, 2025, doi:<a href=\"https://doi.org/10.1038/s41593-025-01874-w\">10.1038/s41593-025-01874-w</a>."},"publication_status":"published","project":[{"call_identifier":"H2020","_id":"2634E9D2-B435-11E9-9278-68D0E5697425","grant_number":"756502","name":"Circuits of Visual Attention"},{"grant_number":"101086580","_id":"bdaf81a8-d553-11ed-ba76-c95961984540","name":"Action Selection in the Midbrain: Neuromodulation of Visuomotor Senses"},{"name":"Connecting sensory with motor processing in the superior colliculus","_id":"264FEA02-B435-11E9-9278-68D0E5697425","grant_number":"ALTF 1098-2017"},{"grant_number":"LT000256","_id":"266D407A-B435-11E9-9278-68D0E5697425","name":"Neuronal networks of salience and spatial detection in the murine superior colliculus"}],"author":[{"id":"2E7C4E78-F248-11E8-B48F-1D18A9856A87","last_name":"Vega Zuniga","first_name":"Tomas A","full_name":"Vega Zuniga, Tomas A"},{"first_name":"Anton L","orcid":"0000-0002-4792-1881","full_name":"Sumser, Anton L","id":"3320A096-F248-11E8-B48F-1D18A9856A87","last_name":"Sumser"},{"first_name":"Olga","orcid":"0000-0003-2012-9947","full_name":"Symonova, Olga","id":"3C0C7BC6-F248-11E8-B48F-1D18A9856A87","last_name":"Symonova"},{"last_name":"Koppensteiner","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3509-1948","full_name":"Koppensteiner, Peter","first_name":"Peter"},{"full_name":"Schmidt, Florian","first_name":"Florian","last_name":"Schmidt","id":"A2EF226A-AF19-11E9-924C-0525E6697425"},{"full_name":"Jösch, Maximilian A","orcid":"0000-0002-3937-1330","first_name":"Maximilian A","last_name":"Jösch","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87"}],"OA_type":"hybrid","type":"journal_article","article_number":"7278","date_created":"2025-02-23T23:01:58Z","pmid":1,"OA_place":"publisher","main_file_link":[{"url":"https://doi.org/10.1038/s41593-025-01874-w","open_access":"1"}],"article_processing_charge":"Yes (via OA deal)","ec_funded":1,"language":[{"iso":"eng"}],"external_id":{"isi":["001416866800001"],"pmid":["39930095"]},"oa":1,"department":[{"_id":"MaJö"},{"_id":"PreCl"}],"date_published":"2025-03-01T00:00:00Z","abstract":[{"text":"For accurate perception and motor control, an animal must distinguish between sensory experiences elicited by external stimuli and those elicited by its own actions. The diversity of behaviors and their complex influences on the senses make this distinction challenging. Here, we uncover an action–cue hub that coordinates motor commands with visual processing in the brain’s first visual relay. We show that the ventral lateral geniculate nucleus (vLGN) acts as a corollary discharge center, integrating visual translational optic flow signals with motor copies from saccades, locomotion and pupil dynamics. The vLGN relays these signals to correct action-specific visual distortions and to refine perception, as shown for the superior colliculus and in a depth-estimation task. Simultaneously, brain-wide vLGN projections drive corrective actions necessary for accurate visuomotor control. Our results reveal an extended corollary discharge architecture that refines early visual transformations and coordinates actions via a distributed hub-and-spoke network to enable visual perception during action.","lang":"eng"}],"intvolume":"        28","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"Bio"}],"status":"public","publication":"Nature Neuroscience","has_accepted_license":"1","scopus_import":"1","ddc":["570"]},{"doi":"10.1016/j.neuron.2023.11.009","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. ","_id":"12875","related_material":{"link":[{"url":"https://ista.ac.at/en/news/the-pedigree-of-brain-cells/","relation":"press_release","description":"News on ISTA Website"}]},"publisher":"Elsevier","day":"17","year":"2024","corr_author":"1","title":"Multipotent progenitors instruct ontogeny of the superior colliculus","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"01","article_type":"original","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"quality_controlled":"1","publication_identifier":{"issn":["0896-6273"]},"fulldoi":"https://doi.org/10.1016/j.neuron.2023.11.009","volume":112,"date_updated":"2025-12-30T10:54:12Z","oa_version":"Published Version","isi":1,"ddc":["570"],"scopus_import":"1","has_accepted_license":"1","publication":"Neuron","acknowledged_ssus":[{"_id":"Bio"},{"_id":"M-Shop"},{"_id":"LifeSc"},{"_id":"PreCl"}],"status":"public","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."}],"intvolume":"       112","department":[{"_id":"SiHi"},{"_id":"RySh"}],"date_published":"2024-01-17T00:00:00Z","language":[{"iso":"eng"}],"oa":1,"external_id":{"isi":["001163937900001"],"pmid":["38096816"]},"article_processing_charge":"Yes (via OA deal)","pmid":1,"file_date_updated":"2024-02-06T13:56:15Z","page":"230-246.e11","date_created":"2023-04-27T09:41:48Z","type":"journal_article","issue":"2","author":[{"first_name":"Giselle T","full_name":"Cheung, Giselle T","orcid":"0000-0001-8457-2572","id":"471195F6-F248-11E8-B48F-1D18A9856A87","last_name":"Cheung"},{"first_name":"Florian","orcid":"0000-0002-7462-0048","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler"},{"id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","last_name":"Koppensteiner","first_name":"Peter","orcid":"0000-0002-3509-1948","full_name":"Koppensteiner, Peter"},{"last_name":"Krausgruber","first_name":"Thomas","full_name":"Krausgruber, Thomas"},{"first_name":"Carmen","full_name":"Streicher, Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","last_name":"Streicher"},{"full_name":"Schrammel, Martin","first_name":"Martin","last_name":"Schrammel","id":"f13e7cae-e8bd-11ed-841a-96dedf69f46d"},{"id":"e68ece33-f6e0-11ea-865d-ae1031dcc090","last_name":"Özgen","first_name":"Natalie Y","full_name":"Özgen, Natalie Y"},{"full_name":"Ivec, Alexis","first_name":"Alexis","last_name":"Ivec","id":"1d144691-e8be-11ed-9b33-bdd3077fad4c"},{"first_name":"Christoph","full_name":"Bock, Christoph","last_name":"Bock"},{"last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","first_name":"Ryuichi"},{"full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87"}],"project":[{"name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression","grant_number":"F7805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E"}],"publication_status":"published","citation":{"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.” <i>Neuron</i>, vol. 112, no. 2, Elsevier, 2024, p. 230–246.e11, doi:<a href=\"https://doi.org/10.1016/j.neuron.2023.11.009\">10.1016/j.neuron.2023.11.009</a>.","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.” <i>Neuron</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.neuron.2023.11.009\">https://doi.org/10.1016/j.neuron.2023.11.009</a>.","ama":"Cheung GT, Pauler F, Koppensteiner P, et al. Multipotent progenitors instruct ontogeny of the superior colliculus. <i>Neuron</i>. 2024;112(2):230-246.e11. doi:<a href=\"https://doi.org/10.1016/j.neuron.2023.11.009\">10.1016/j.neuron.2023.11.009</a>","ieee":"G. T. Cheung <i>et al.</i>, “Multipotent progenitors instruct ontogeny of the superior colliculus,” <i>Neuron</i>, vol. 112, no. 2. Elsevier, p. 230–246.e11, 2024.","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. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2023.11.009\">https://doi.org/10.1016/j.neuron.2023.11.009</a>","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."},"file":[{"file_id":"14944","checksum":"32b3788f7085cf44a84108d8faaff3ce","relation":"main_file","date_created":"2024-02-06T13:56:15Z","date_updated":"2024-02-06T13:56:15Z","creator":"dernst","file_size":5942467,"access_level":"open_access","success":1,"content_type":"application/pdf","file_name":"2024_Neuron_Cheung.pdf"}]},{"doi":"10.15479/AT:ISTA:15385","publisher":"Institute of Science and Technology Austria","related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"17142"}]},"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. ","_id":"15385","day":"15","year":"2024","corr_author":"1","title":"Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice","month":"05","user_id":"68b8ca59-c5b3-11ee-8790-cd641c68093d","tmp":{"image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)","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)"},"fulldoi":"https://doi.org/10.15479/AT:ISTA:15385","date_updated":"2025-09-08T07:57:11Z","oa_version":"Published Version","ddc":["570"],"has_accepted_license":"1","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"M-Shop"},{"_id":"LifeSc"},{"_id":"Bio"}],"status":"public","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)"}],"department":[{"_id":"MaJö"},{"_id":"PreCl"},{"_id":"SiHi"},{"_id":"RySh"},{"_id":"GaNo"}],"date_published":"2024-05-15T00:00:00Z","oa":1,"article_processing_charge":"No","file_date_updated":"2024-05-16T09:08:20Z","date_created":"2024-05-13T15:04:04Z","keyword":["ASD","periaqueductal gray","perception","behavior","potassium channels"],"type":"research_data","author":[{"first_name":"Laura","full_name":"Burnett, Laura","orcid":"0000-0002-8937-410X","id":"3B717F68-F248-11E8-B48F-1D18A9856A87","last_name":"Burnett"},{"orcid":"0000-0002-3509-1948","full_name":"Koppensteiner, Peter","first_name":"Peter","last_name":"Koppensteiner","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87"},{"id":"3C0C7BC6-F248-11E8-B48F-1D18A9856A87","last_name":"Symonova","first_name":"Olga","orcid":"0000-0003-2012-9947","full_name":"Symonova, Olga"},{"first_name":"Tomas","orcid":"0000-0002-2634-6283","full_name":"Masson, Tomas","id":"93ac43e8-8599-11eb-9b86-f6efb0a4c207","last_name":"Masson"},{"full_name":"Vega Zuniga, Tomas A","first_name":"Tomas A","last_name":"Vega Zuniga","id":"2E7C4E78-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Contreras, Ximena","first_name":"Ximena","last_name":"Contreras","id":"475990FE-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Rülicke","full_name":"Rülicke, Thomas","first_name":"Thomas"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto","first_name":"Ryuichi","full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"},{"orcid":"0000-0002-3937-1330","full_name":"Jösch, Maximilian A","first_name":"Maximilian A","last_name":"Jösch","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87"}],"citation":{"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. <a href=\"https://doi.org/10.15479/AT:ISTA:15385\">https://doi.org/10.15479/AT:ISTA:15385</a>.","mla":"Burnett, Laura, et al. <i>Shared Behavioural Impairments in Visual Perception and Place Avoidance across Different Autism Models Are Driven by Periaqueductal Grey Hypoexcitability in Setd5 Haploinsufficient Mice</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:15385\">10.15479/AT:ISTA:15385</a>.","ieee":"L. Burnett <i>et al.</i>, “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.","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:<a href=\"https://doi.org/10.15479/AT:ISTA:15385\">10.15479/AT:ISTA:15385</a>","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, <a href=\"https://doi.org/10.15479/AT:ISTA:15385\">10.15479/AT:ISTA:15385</a>.","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).","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. <a href=\"https://doi.org/10.15479/AT:ISTA:15385\">https://doi.org/10.15479/AT:ISTA:15385</a>"},"file":[{"date_updated":"2024-05-15T06:09:17Z","date_created":"2024-05-15T06:09:17Z","relation":"main_file","checksum":"9205eb0876f0f08552dbad80d6884b4b","file_id":"15396","content_type":"application/zip","file_name":"PatchClamp.zip","success":1,"access_level":"open_access","file_size":"1149617663","creator":"mjoesch"},{"content_type":"application/zip","file_name":"SiliconProbe.zip","creator":"mjoesch","file_size":"564903112","access_level":"open_access","success":1,"file_id":"15397","relation":"main_file","date_created":"2024-05-15T06:09:12Z","date_updated":"2024-05-15T06:09:12Z"},{"date_created":"2024-05-15T06:09:14Z","relation":"main_file","checksum":"49a807bbab06b5fada38f532e2176e2e","file_id":"15398","date_updated":"2024-05-15T06:09:14Z","content_type":"application/zip","file_name":"WesternBlot.zip","creator":"mjoesch","access_level":"open_access","success":1,"file_size":"11685703"},{"creator":"mjoesch","access_level":"open_access","success":1,"file_size":"1335626779","content_type":"application/zip","file_name":"Behaviour.zip","date_created":"2024-05-15T06:09:38Z","relation":"main_file","file_id":"15399","checksum":"beeeeaa43770090f3b291209ed6b0623","date_updated":"2024-05-15T06:09:38Z"},{"content_type":"text/plain","file_name":"Readme_Data.txt","access_level":"open_access","success":1,"file_size":18841,"creator":"mjoesch","date_updated":"2024-05-16T09:08:20Z","relation":"main_file","date_created":"2024-05-16T09:08:20Z","file_id":"15400","checksum":"8862ad7719388304d1d19f8e7db8bb00"}]},{"_id":"17142","publisher":"Public Library of Science","acknowledgement":"This work was supported by a European Research Council Starting Grant 756502 (MJ). ","related_material":{"record":[{"status":"public","relation":"research_data","id":"15385"}],"link":[{"relation":"software","url":"https://doi.org/10.5281/zenodo.11130587"}]},"doi":"10.1371/journal.pbio.3002668","title":"Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice","corr_author":"1","APC_amount":"6081,83 EUR","year":"2024","day":"10","article_type":"original","month":"06","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","DOAJ_listed":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"fulldoi":"https://doi.org/10.1371/journal.pbio.3002668","publication_identifier":{"eissn":["1545-7885"],"issn":["1544-9173"]},"quality_controlled":"1","date_updated":"2025-09-08T07:57:11Z","volume":22,"oa_version":"Published Version","isi":1,"has_accepted_license":"1","scopus_import":"1","ddc":["570"],"status":"public","publication":"PLoS Biology","ec_funded":1,"article_processing_charge":"Yes","language":[{"iso":"eng"}],"external_id":{"isi":["001246176800003"],"pmid":["38857283"]},"oa":1,"date_published":"2024-06-10T00:00:00Z","department":[{"_id":"RySh"},{"_id":"GaNo"},{"_id":"MaJö"}],"intvolume":"        22","abstract":[{"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.","lang":"eng"}],"pmid":1,"OA_place":"publisher","file_date_updated":"2025-01-09T10:39:41Z","author":[{"id":"3B717F68-F248-11E8-B48F-1D18A9856A87","last_name":"Burnett","first_name":"Laura","full_name":"Burnett, Laura","orcid":"0000-0002-8937-410X"},{"id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","last_name":"Koppensteiner","first_name":"Peter","orcid":"0000-0002-3509-1948","full_name":"Koppensteiner, Peter"},{"id":"3C0C7BC6-F248-11E8-B48F-1D18A9856A87","last_name":"Symonova","first_name":"Olga","orcid":"0000-0003-2012-9947","full_name":"Symonova, Olga"},{"full_name":"Masson, Tomas","orcid":"0000-0002-2634-6283","first_name":"Tomas","last_name":"Masson","id":"93ac43e8-8599-11eb-9b86-f6efb0a4c207"},{"full_name":"Vega Zuniga, Tomas A","first_name":"Tomas A","last_name":"Vega Zuniga","id":"2E7C4E78-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Contreras","id":"475990FE-F248-11E8-B48F-1D18A9856A87","full_name":"Contreras, Ximena","first_name":"Ximena"},{"last_name":"Rülicke","full_name":"Rülicke, Thomas","first_name":"Thomas"},{"first_name":"Ryuichi","full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto"},{"last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","first_name":"Gaia"},{"orcid":"0000-0002-3937-1330","full_name":"Jösch, Maximilian A","first_name":"Maximilian A","last_name":"Jösch","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87"}],"OA_type":"gold","type":"journal_article","date_created":"2024-06-16T22:01:05Z","article_number":"e3002668","publication_status":"published","project":[{"grant_number":"756502","_id":"2634E9D2-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Circuits of Visual Attention"}],"file":[{"creator":"dernst","file_size":4016568,"access_level":"open_access","success":1,"file_name":"2024_PloS_Burnett.pdf","content_type":"application/pdf","checksum":"496e1aa4fd5b92b7e4087ecc2c964133","file_id":"18805","relation":"main_file","date_created":"2025-01-09T10:39:41Z","date_updated":"2025-01-09T10:39:41Z"}],"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. <i>PLoS Biology</i>. 2024;22. doi:<a href=\"https://doi.org/10.1371/journal.pbio.3002668\">10.1371/journal.pbio.3002668</a>","ieee":"L. Burnett <i>et al.</i>, “Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice,” <i>PLoS Biology</i>, vol. 22. Public Library of Science, 2024.","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.” <i>PLoS Biology</i>. Public Library of Science, 2024. <a href=\"https://doi.org/10.1371/journal.pbio.3002668\">https://doi.org/10.1371/journal.pbio.3002668</a>.","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.” <i>PLoS Biology</i>, vol. 22, e3002668, Public Library of Science, 2024, doi:<a href=\"https://doi.org/10.1371/journal.pbio.3002668\">10.1371/journal.pbio.3002668</a>.","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.","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).","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. <i>PLoS Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pbio.3002668\">https://doi.org/10.1371/journal.pbio.3002668</a>"}},{"file_date_updated":"2024-12-09T12:54:55Z","date_created":"2024-11-22T13:48:12Z","type":"research_data","author":[{"last_name":"Vega Zuniga","id":"2E7C4E78-F248-11E8-B48F-1D18A9856A87","full_name":"Vega Zuniga, Tomas A","first_name":"Tomas A"},{"last_name":"Sumser","id":"3320A096-F248-11E8-B48F-1D18A9856A87","full_name":"Sumser, Anton L","orcid":"0000-0002-4792-1881","first_name":"Anton L"},{"orcid":"0000-0003-2012-9947","full_name":"Symonova, Olga","first_name":"Olga","last_name":"Symonova","id":"3C0C7BC6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Peter","orcid":"0000-0002-3509-1948","full_name":"Koppensteiner, Peter","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","last_name":"Koppensteiner"},{"last_name":"Schmidt","id":"A2EF226A-AF19-11E9-924C-0525E6697425","full_name":"Schmidt, Florian","first_name":"Florian"},{"first_name":"Maximilian A","full_name":"Jösch, Maximilian A","orcid":"0000-0002-3937-1330","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","last_name":"Jösch"}],"project":[{"name":"Connecting sensory with motor processing in the superior colliculus","_id":"264FEA02-B435-11E9-9278-68D0E5697425","grant_number":"ALTF 1098-2017"},{"_id":"266D407A-B435-11E9-9278-68D0E5697425","grant_number":"LT000256","name":"Neuronal networks of salience and spatial detection in the murine superior colliculus"},{"grant_number":"756502","call_identifier":"H2020","_id":"2634E9D2-B435-11E9-9278-68D0E5697425","name":"Circuits of Visual Attention"},{"name":"Action Selection in the Midbrain: Neuromodulation of Visuomotor Senses","grant_number":"101086580","_id":"bdaf81a8-d553-11ed-ba76-c95961984540"}],"citation":{"short":"T.A. Vega Zuniga, A.L. Sumser, O. Symonova, P. Koppensteiner, F. Schmidt, M.A. Jösch, (2024).","apa":"Vega Zuniga, T. A., Sumser, A. L., Symonova, O., Koppensteiner, P., Schmidt, F., &#38; Jösch, M. A. (2024). A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:18579\">https://doi.org/10.15479/AT:ISTA:18579</a>","ista":"Vega Zuniga TA, Sumser AL, Symonova O, Koppensteiner P, Schmidt F, Jösch MA. 2024. A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:18579\">10.15479/AT:ISTA:18579</a>.","ieee":"T. A. Vega Zuniga, A. L. Sumser, O. Symonova, P. Koppensteiner, F. Schmidt, and M. A. Jösch, “A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics.” Institute of Science and Technology Austria, 2024.","chicago":"Vega Zuniga, Tomas A, Anton L Sumser, Olga Symonova, Peter Koppensteiner, Florian Schmidt, and Maximilian A Jösch. “A Thalamic Hub-and-Spoke Network Enables Visual Perception during Action by Coordinating Visuomotor Dynamics.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/AT:ISTA:18579\">https://doi.org/10.15479/AT:ISTA:18579</a>.","ama":"Vega Zuniga TA, Sumser AL, Symonova O, Koppensteiner P, Schmidt F, Jösch MA. A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics. 2024. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:18579\">10.15479/AT:ISTA:18579</a>","mla":"Vega Zuniga, Tomas A., et al. <i>A Thalamic Hub-and-Spoke Network Enables Visual Perception during Action by Coordinating Visuomotor Dynamics</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:18579\">10.15479/AT:ISTA:18579</a>."},"file":[{"file_name":"electro_physiology_data.zip","content_type":"application/x-zip-compressed","creator":"symonova","file_size":800647957,"access_level":"open_access","file_id":"18625","checksum":"8b13990ca1a458ae3f3ae54c2e888564","relation":"main_file","date_created":"2024-12-06T13:28:18Z","date_updated":"2024-12-09T10:24:25Z"},{"checksum":"c5a4d71c5f29c009c3d96a3244532afa","file_id":"18636","relation":"main_file","date_created":"2024-12-09T10:21:10Z","date_updated":"2024-12-09T10:21:10Z","content_type":"application/x-zip-compressed","file_name":"NN_vLGN_Ca_data.zip","creator":"symonova","file_size":828410832,"success":1,"access_level":"open_access"},{"date_updated":"2024-12-09T12:54:55Z","relation":"main_file","date_created":"2024-12-09T12:54:55Z","checksum":"63651df0186196969553dc48b467f6ab","file_id":"18637","access_level":"open_access","success":1,"file_size":505,"creator":"symonova","file_name":"readme.txt","content_type":"text/plain"}],"ddc":["570"],"has_accepted_license":"1","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"PreCl"},{"_id":"M-Shop"},{"_id":"Bio"},{"_id":"LifeSc"}],"status":"public","abstract":[{"text":"Electrophysiological, calcium two-photon recordings and behavioral data for Vega-Zuniga et al.  Relevant information can be found in the 'README.txt' files. ","lang":"eng"}],"department":[{"_id":"MaJö"}],"date_published":"2024-12-09T00:00:00Z","oa":1,"article_processing_charge":"No","ec_funded":1,"OA_place":"publisher","fulldoi":"https://doi.org/10.15479/AT:ISTA:18579","date_updated":"2026-06-18T18:12:08Z","oa_version":"Published Version","doi":"10.15479/AT:ISTA:18579","publisher":"Institute of Science and Technology Austria","_id":"18579","related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"19076"}]},"acknowledgement":"Freyja Lange, Michael Schunn, and Todor Asenov","day":"09","year":"2024","corr_author":"1","title":"A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"12","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"}},{"publication":"STAR Protocols","acknowledged_ssus":[{"_id":"Bio"},{"_id":"M-Shop"},{"_id":"PreCl"}],"status":"public","scopus_import":"1","has_accepted_license":"1","ddc":["570"],"pmid":1,"OA_place":"publisher","article_processing_charge":"Yes","oa":1,"language":[{"iso":"eng"}],"external_id":{"pmid":["38968076"]},"department":[{"_id":"SiHi"},{"_id":"PreCl"}],"date_published":"2024-09-20T00:00:00Z","intvolume":"         5","abstract":[{"text":"The lineage relationship of clonally-related cells offers important insights into the ontogeny and cytoarchitecture of the brain in health and disease. Here, we provide a protocol to concurrently assess cell lineage relationship and cell-type identity among clonally-related cells in situ. We first describe the preparation and screening of acute brain slices containing clonally-related cells labeled using mosaic analysis with double markers (MADM). We then outline steps to collect RNA from individual cells for downstream applications and cell-type identification using RNA sequencing.\r\nFor complete details on the use and execution of this protocol, please refer to Cheung et al.\r\n1","lang":"eng"}],"author":[{"last_name":"Cheung","id":"471195F6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8457-2572","full_name":"Cheung, Giselle T","first_name":"Giselle T"},{"last_name":"Pauler","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","full_name":"Pauler, Florian","orcid":"0000-0002-7462-0048","first_name":"Florian"},{"last_name":"Koppensteiner","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3509-1948","full_name":"Koppensteiner, Peter","first_name":"Peter"},{"last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","first_name":"Simon"}],"issue":"3","OA_type":"gold","type":"journal_article","article_number":"103168","date_created":"2024-07-14T22:01:10Z","file_date_updated":"2025-01-09T12:16:53Z","file":[{"file_size":6445556,"success":1,"access_level":"open_access","creator":"dernst","content_type":"application/pdf","file_name":"2024_STARProtoc_Cheung2.pdf","date_updated":"2025-01-09T12:16:53Z","file_id":"18810","checksum":"464f52ecc6ec92f509552823bb82bf79","relation":"main_file","date_created":"2025-01-09T12:16:53Z"}],"citation":{"apa":"Cheung, G. T., Pauler, F., Koppensteiner, P., &#38; Hippenmeyer, S. (2024). Protocol for mapping cell lineage and cell-type identity of clonally-related cells in situ using MADM-CloneSeq. <i>STAR Protocols</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xpro.2024.103168\">https://doi.org/10.1016/j.xpro.2024.103168</a>","short":"G.T. Cheung, F. Pauler, P. Koppensteiner, S. Hippenmeyer, STAR Protocols 5 (2024).","ista":"Cheung GT, Pauler F, Koppensteiner P, Hippenmeyer S. 2024. Protocol for mapping cell lineage and cell-type identity of clonally-related cells in situ using MADM-CloneSeq. STAR Protocols. 5(3), 103168.","mla":"Cheung, Giselle T., et al. “Protocol for Mapping Cell Lineage and Cell-Type Identity of Clonally-Related Cells in Situ Using MADM-CloneSeq.” <i>STAR Protocols</i>, vol. 5, no. 3, 103168, Elsevier, 2024, doi:<a href=\"https://doi.org/10.1016/j.xpro.2024.103168\">10.1016/j.xpro.2024.103168</a>.","ama":"Cheung GT, Pauler F, Koppensteiner P, Hippenmeyer S. Protocol for mapping cell lineage and cell-type identity of clonally-related cells in situ using MADM-CloneSeq. <i>STAR Protocols</i>. 2024;5(3). doi:<a href=\"https://doi.org/10.1016/j.xpro.2024.103168\">10.1016/j.xpro.2024.103168</a>","chicago":"Cheung, Giselle T, Florian Pauler, Peter Koppensteiner, and Simon Hippenmeyer. “Protocol for Mapping Cell Lineage and Cell-Type Identity of Clonally-Related Cells in Situ Using MADM-CloneSeq.” <i>STAR Protocols</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.xpro.2024.103168\">https://doi.org/10.1016/j.xpro.2024.103168</a>.","ieee":"G. T. Cheung, F. Pauler, P. Koppensteiner, and S. Hippenmeyer, “Protocol for mapping cell lineage and cell-type identity of clonally-related cells in situ using MADM-CloneSeq,” <i>STAR Protocols</i>, vol. 5, no. 3. Elsevier, 2024."},"publication_status":"published","project":[{"name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","grant_number":"F7805"}],"title":"Protocol for mapping cell lineage and cell-type identity of clonally-related cells in situ using MADM-CloneSeq","APC_amount":"804 EUR","corr_author":"1","year":"2024","day":"20","acknowledgement":"We thank R. Beattie and T. Asenov for designing and producing components of the multi-well slice recover chamber. We thank R. Shigemoto for providing equipment access. We thank C. Streicher and A. Heger for mouse breeding support. This work was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging & Optics, Miba Machine Shop, and Preclinical facilities. G.C. received funding from the European Commission (IST plus postdoctoral fellowship) and S.H. was funded by ISTA institutional funds and the Austrian Science Fund Special Research Programmes (FWF SFB-F78 Neuro Stem Modulation).","_id":"17232","publisher":"Elsevier","doi":"10.1016/j.xpro.2024.103168","tmp":{"short":"CC BY-NC-ND (4.0)","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)"},"article_type":"original","month":"09","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_updated":"2025-12-30T10:54:12Z","volume":5,"fulldoi":"https://doi.org/10.1016/j.xpro.2024.103168","quality_controlled":"1","publication_identifier":{"eissn":["2666-1667"]},"oa_version":"Published Version"},{"status":"public","publication":"Science Advances","has_accepted_license":"1","scopus_import":"1","ddc":["570"],"pmid":1,"OA_place":"publisher","date_published":"2024-07-12T00:00:00Z","department":[{"_id":"RySh"},{"_id":"PreCl"}],"abstract":[{"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.","lang":"eng"}],"intvolume":"        10","article_processing_charge":"Yes","oa":1,"external_id":{"isi":["001280159000022"],"pmid":["38985877"]},"language":[{"iso":"eng"}],"article_number":"adk5462","date_created":"2024-07-21T22:01:01Z","issue":"28","author":[{"full_name":"Früh, Simon","first_name":"Simon","last_name":"Früh"},{"last_name":"Boudkkazi","first_name":"Sami","full_name":"Boudkkazi, Sami"},{"orcid":"0000-0002-3509-1948","full_name":"Koppensteiner, Peter","first_name":"Peter","last_name":"Koppensteiner","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Sereikaite","full_name":"Sereikaite, Vita","first_name":"Vita"},{"first_name":"Li Yuan","full_name":"Chen, Li Yuan","last_name":"Chen"},{"full_name":"Fernandez-Fernandez, Diego","first_name":"Diego","last_name":"Fernandez-Fernandez"},{"last_name":"Rem","full_name":"Rem, Pascal D.","first_name":"Pascal D."},{"last_name":"Ulrich","first_name":"Daniel","full_name":"Ulrich, Daniel"},{"last_name":"Schwenk","full_name":"Schwenk, Jochen","first_name":"Jochen"},{"last_name":"Chen","full_name":"Chen, Ziyang","first_name":"Ziyang"},{"first_name":"Elodie Le","full_name":"Monnier, Elodie Le","last_name":"Monnier"},{"last_name":"Fritzius","full_name":"Fritzius, Thorsten","first_name":"Thorsten"},{"first_name":"Sabrina M.","full_name":"Innocenti, Sabrina M.","last_name":"Innocenti"},{"full_name":"Besseyrias, Valérie","first_name":"Valérie","last_name":"Besseyrias"},{"last_name":"Trovò","first_name":"Luca","full_name":"Trovò, Luca"},{"first_name":"Michal","full_name":"Stawarski, Michal","last_name":"Stawarski"},{"last_name":"Argilli","first_name":"Emanuela","full_name":"Argilli, Emanuela"},{"first_name":"Elliott H.","full_name":"Sherr, Elliott H.","last_name":"Sherr"},{"last_name":"Van Bon","first_name":"Bregje","full_name":"Van Bon, Bregje"},{"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"},{"full_name":"Azamian, Mahshid S.","first_name":"Mahshid S.","last_name":"Azamian"},{"full_name":"Hernández-García, Andrés","first_name":"Andrés","last_name":"Hernández-García"},{"last_name":"Lalani","full_name":"Lalani, Seema R.","first_name":"Seema R."},{"last_name":"Rosenfeld","full_name":"Rosenfeld, Jill A.","first_name":"Jill A."},{"last_name":"Zhao","first_name":"Xiaonan","full_name":"Zhao, Xiaonan"},{"first_name":"Tiphanie P.","full_name":"Vogel, Tiphanie P.","last_name":"Vogel"},{"first_name":"Herda","full_name":"Ona, Herda","last_name":"Ona"},{"full_name":"Scott, Daryl A.","first_name":"Daryl A.","last_name":"Scott"},{"full_name":"Scheiffele, Peter","first_name":"Peter","last_name":"Scheiffele"},{"last_name":"Strømgaard","first_name":"Kristian","full_name":"Strømgaard, Kristian"},{"full_name":"Tafti, Mehdi","first_name":"Mehdi","last_name":"Tafti"},{"first_name":"Martin","full_name":"Gassmann, Martin","last_name":"Gassmann"},{"full_name":"Fakler, Bernd","first_name":"Bernd","last_name":"Fakler"},{"first_name":"Ryuichi","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto"},{"full_name":"Bettler, Bernhard","first_name":"Bernhard","last_name":"Bettler"}],"OA_type":"gold","type":"journal_article","file_date_updated":"2024-07-22T06:29:27Z","file":[{"date_updated":"2024-07-22T06:29:27Z","file_id":"17287","checksum":"9cbc4501fcd4ba1c0811fd244031422b","date_created":"2024-07-22T06:29:27Z","relation":"main_file","file_size":7241489,"access_level":"open_access","success":1,"creator":"dernst","content_type":"application/pdf","file_name":"2024_ScienceAdv_Früh.pdf"}],"citation":{"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.” <i>Science Advances</i>. American Association for the Advancement of Science, 2024. <a href=\"https://doi.org/10.1126/sciadv.adk5462\">https://doi.org/10.1126/sciadv.adk5462</a>.","ama":"Früh S, Boudkkazi S, Koppensteiner P, et al. Monoallelic de novo AJAP1 loss-of- function variants disrupt trans-synaptic control of neurotransmitter release. <i>Science Advances</i>. 2024;10(28). doi:<a href=\"https://doi.org/10.1126/sciadv.adk5462\">10.1126/sciadv.adk5462</a>","mla":"Früh, Simon, et al. “Monoallelic de Novo AJAP1 Loss-of- Function Variants Disrupt Trans-Synaptic Control of Neurotransmitter Release.” <i>Science Advances</i>, vol. 10, no. 28, adk5462, American Association for the Advancement of Science, 2024, doi:<a href=\"https://doi.org/10.1126/sciadv.adk5462\">10.1126/sciadv.adk5462</a>.","ieee":"S. Früh <i>et al.</i>, “Monoallelic de novo AJAP1 loss-of- function variants disrupt trans-synaptic control of neurotransmitter release,” <i>Science Advances</i>, 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.","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. <i>Science Advances</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/sciadv.adk5462\">https://doi.org/10.1126/sciadv.adk5462</a>","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)."},"publication_status":"published","year":"2024","day":"12","title":"Monoallelic de novo AJAP1 loss-of- function variants disrupt trans-synaptic control of neurotransmitter release","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.","_id":"17280","publisher":"American Association for the Advancement of Science","doi":"10.1126/sciadv.adk5462","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"DOAJ_listed":"1","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","month":"07","article_type":"original","volume":10,"date_updated":"2025-09-08T08:15:54Z","quality_controlled":"1","publication_identifier":{"eissn":["2375-2548"]},"fulldoi":"https://doi.org/10.1126/sciadv.adk5462","isi":1,"oa_version":"Published Version"},{"fulldoi":"https://doi.org/10.1073/pnas.2301449121","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"quality_controlled":"1","date_updated":"2026-09-13T22:30:36Z","volume":121,"oa_version":"Published Version","isi":1,"related_material":{"record":[{"status":"public","relation":"research_data","id":"13173"},{"relation":"dissertation_contains","id":"19271","status":"public"}],"link":[{"url":"https://ista.ac.at/en/news/neuronal-insights-flash-and-freeze-fracture/","description":"News on ISTA Website","relation":"press_release"}]},"_id":"15084","publisher":"National Academy of Sciences","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.","doi":"10.1073/pnas.2301449121","title":"GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles","corr_author":"1","APC_amount":"5887,8 EUR","year":"2024","day":"20","article_type":"original","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","month":"02","tmp":{"short":"CC BY-NC-ND (4.0)","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)"},"file_date_updated":"2024-03-12T13:42:42Z","issue":"8","author":[{"first_name":"Peter","orcid":"0000-0002-3509-1948","full_name":"Koppensteiner, Peter","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","last_name":"Koppensteiner"},{"id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","last_name":"Bhandari","first_name":"Pradeep","orcid":"0000-0003-0863-4481","full_name":"Bhandari, Pradeep"},{"orcid":"0000-0002-2771-2011","full_name":"Önal, Hüseyin C","first_name":"Hüseyin C","last_name":"Önal","id":"4659D740-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Carolina","full_name":"Borges Merjane, Carolina","orcid":"0000-0003-0005-401X","id":"4305C450-F248-11E8-B48F-1D18A9856A87","last_name":"Borges Merjane"},{"first_name":"Elodie","full_name":"Le Monnier, Elodie","id":"3B59276A-F248-11E8-B48F-1D18A9856A87","last_name":"Le Monnier"},{"last_name":"Roy","id":"4d26cf11-5355-11ee-ae5a-eb05e255b9b2","full_name":"Roy, Utsa","first_name":"Utsa"},{"first_name":"Yukihiro","full_name":"Nakamura, Yukihiro","last_name":"Nakamura"},{"last_name":"Sadakata","full_name":"Sadakata, Tetsushi","first_name":"Tetsushi"},{"first_name":"Makoto","full_name":"Sanbo, Makoto","last_name":"Sanbo"},{"full_name":"Hirabayashi, Masumi","first_name":"Masumi","last_name":"Hirabayashi"},{"last_name":"Rhee","full_name":"Rhee, JeongSeop","first_name":"JeongSeop"},{"first_name":"Nils","full_name":"Brose, Nils","last_name":"Brose"},{"first_name":"Peter M","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas"},{"last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","first_name":"Ryuichi"}],"type":"journal_article","OA_type":"hybrid","article_number":"e2301449121","date_created":"2024-03-05T09:23:55Z","publication_status":"published","project":[{"name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","grant_number":"694539","call_identifier":"H2020","_id":"25CA28EA-B435-11E9-9278-68D0E5697425"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"665385","name":"International IST Doctoral Program"}],"file":[{"access_level":"open_access","success":1,"file_size":13648221,"creator":"dernst","file_name":"2024_PNAS_Koppensteiner.pdf","content_type":"application/pdf","date_updated":"2024-03-12T13:42:42Z","date_created":"2024-03-12T13:42:42Z","relation":"main_file","file_id":"15110","checksum":"b25b2a057c266ff317a48b0d54d6fc8a"}],"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. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2024;121(8). doi:<a href=\"https://doi.org/10.1073/pnas.2301449121\">10.1073/pnas.2301449121</a>","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.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences, 2024. <a href=\"https://doi.org/10.1073/pnas.2301449121\">https://doi.org/10.1073/pnas.2301449121</a>.","mla":"Koppensteiner, Peter, et al. “GABAB Receptors Induce Phasic Release from Medial Habenula Terminals through Activity-Dependent Recruitment of Release-Ready Vesicles.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 121, no. 8, e2301449121, National Academy of Sciences, 2024, doi:<a href=\"https://doi.org/10.1073/pnas.2301449121\">10.1073/pnas.2301449121</a>.","ieee":"P. Koppensteiner <i>et al.</i>, “GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, 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.","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. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2301449121\">https://doi.org/10.1073/pnas.2301449121</a>","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)."},"has_accepted_license":"1","scopus_import":"1","ddc":["570"],"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"publication":"Proceedings of the National Academy of Sciences of the United States of America","status":"public","ec_funded":1,"article_processing_charge":"Yes (in subscription journal)","language":[{"iso":"eng"}],"external_id":{"isi":["001208567300006"],"pmid":["38346189"]},"oa":1,"date_published":"2024-02-20T00:00:00Z","department":[{"_id":"RySh"},{"_id":"PeJo"}],"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            <jats:sup>2+</jats:sup>\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."}],"intvolume":"       121","pmid":1,"OA_place":"publisher"},{"file":[{"relation":"main_file","date_created":"2022-05-31T09:10:15Z","checksum":"769ab627c7355a50ccfd445e43a5f351","file_id":"11423","date_updated":"2022-05-31T09:10:15Z","creator":"dernst","access_level":"open_access","success":1,"file_size":11571961,"content_type":"application/pdf","file_name":"2021_JourNeuroscience_Butola.pdf"}],"citation":{"mla":"Butola, Tanvi, et al. “RIM-Binding Protein 2 Organizes Ca<sup>21</sup> Channel Topography and Regulates Release Probability and Vesicle Replenishment at a Fast Central Synapse.” <i>Journal of Neuroscience</i>, vol. 41, no. 37, Society for Neuroscience, 2021, pp. 7742–67, doi:<a href=\"https://doi.org/10.1523/JNEUROSCI.0586-21.2021\">10.1523/JNEUROSCI.0586-21.2021</a>.","ama":"Butola T, Alvanos T, Hintze A, et al. RIM-binding protein 2 organizes Ca<sup>21</sup> channel topography and regulates release probability and vesicle replenishment at a fast central synapse. <i>Journal of Neuroscience</i>. 2021;41(37):7742-7767. doi:<a href=\"https://doi.org/10.1523/JNEUROSCI.0586-21.2021\">10.1523/JNEUROSCI.0586-21.2021</a>","chicago":"Butola, Tanvi, Theocharis Alvanos, Anika Hintze, Peter Koppensteiner, David Kleindienst, Ryuichi Shigemoto, Carolin Wichmann, and Tobias Moser. “RIM-Binding Protein 2 Organizes Ca<sup>21</sup> Channel Topography and Regulates Release Probability and Vesicle Replenishment at a Fast Central Synapse.” <i>Journal of Neuroscience</i>. Society for Neuroscience, 2021. <a href=\"https://doi.org/10.1523/JNEUROSCI.0586-21.2021\">https://doi.org/10.1523/JNEUROSCI.0586-21.2021</a>.","ieee":"T. Butola <i>et al.</i>, “RIM-binding protein 2 organizes Ca<sup>21</sup> channel topography and regulates release probability and vesicle replenishment at a fast central synapse,” <i>Journal of Neuroscience</i>, vol. 41, no. 37. Society for Neuroscience, pp. 7742–7767, 2021.","ista":"Butola T, Alvanos T, Hintze A, Koppensteiner P, Kleindienst D, Shigemoto R, Wichmann C, Moser T. 2021. RIM-binding protein 2 organizes Ca<sup>21</sup> channel topography and regulates release probability and vesicle replenishment at a fast central synapse. Journal of Neuroscience. 41(37), 7742–7767.","apa":"Butola, T., Alvanos, T., Hintze, A., Koppensteiner, P., Kleindienst, D., Shigemoto, R., … Moser, T. (2021). RIM-binding protein 2 organizes Ca<sup>21</sup> channel topography and regulates release probability and vesicle replenishment at a fast central synapse. <i>Journal of Neuroscience</i>. Society for Neuroscience. <a href=\"https://doi.org/10.1523/JNEUROSCI.0586-21.2021\">https://doi.org/10.1523/JNEUROSCI.0586-21.2021</a>","short":"T. Butola, T. Alvanos, A. Hintze, P. Koppensteiner, D. Kleindienst, R. Shigemoto, C. Wichmann, T. Moser, Journal of Neuroscience 41 (2021) 7742–7767."},"publication_status":"published","author":[{"first_name":"Tanvi","full_name":"Butola, Tanvi","last_name":"Butola"},{"first_name":"Theocharis","full_name":"Alvanos, Theocharis","last_name":"Alvanos"},{"first_name":"Anika","full_name":"Hintze, Anika","last_name":"Hintze"},{"full_name":"Koppensteiner, Peter","orcid":"0000-0002-3509-1948","first_name":"Peter","last_name":"Koppensteiner","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Kleindienst, David","first_name":"David","last_name":"Kleindienst","id":"42E121A4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","first_name":"Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Wichmann","full_name":"Wichmann, Carolin","first_name":"Carolin"},{"full_name":"Moser, Tobias","first_name":"Tobias","last_name":"Moser"}],"issue":"37","type":"journal_article","date_created":"2021-09-27T14:33:13Z","page":"7742-7767","file_date_updated":"2022-05-31T09:10:15Z","pmid":1,"article_processing_charge":"No","external_id":{"isi":["000752287700005"],"pmid":["34353898"]},"language":[{"iso":"eng"}],"oa":1,"date_published":"2021-09-15T00:00:00Z","department":[{"_id":"RySh"}],"abstract":[{"lang":"eng","text":"Rab-interacting molecule (RIM)-binding protein 2 (BP2) is a multidomain protein of the presynaptic active zone (AZ). By binding to RIM, bassoon (Bsn), and voltage-gated Ca2+ channels (CaV), it is considered to be a central organizer of the topography of CaV and release sites of synaptic vesicles (SVs) at the AZ. Here, we used RIM-BP2 knock-out (KO) mice and their wild-type (WT) littermates of either sex to investigate the role of RIM-BP2 at the endbulb of Held synapse of auditory nerve fibers (ANFs) with bushy cells (BCs) of the cochlear nucleus, a fast relay of the auditory pathway with high release probability. Disruption of RIM-BP2 lowered release probability altering short-term plasticity and reduced evoked EPSCs. Analysis of SV pool dynamics during high-frequency train stimulation indicated a reduction of SVs with high release probability but an overall normal size of the readily releasable SV pool (RRP). The Ca2+-dependent fast component of SV replenishment after RRP depletion was slowed. Ultrastructural analysis by superresolution light and electron microscopy revealed an impaired topography of presynaptic CaV and a reduction of docked and membrane-proximal SVs at the AZ. We conclude that RIM-BP2 organizes the topography of CaV, and promotes SV tethering and docking. This way RIM-BP2 is critical for establishing a high initial release probability as required to reliably signal sound onset information that we found to be degraded in BCs of RIM-BP2-deficient mice in vivo. SIGNIFICANCE STATEMENT: Rab-interacting molecule (RIM)-binding proteins (BPs) are key organizers of the active zone (AZ). Using a multidisciplinary approach to the calyceal endbulb of Held synapse that transmits auditory information at rates of up to hundreds of Hertz with submillisecond precision we demonstrate a requirement for RIM-BP2 for normal auditory signaling. Endbulb synapses lacking RIM-BP2 show a reduced release probability despite normal whole-terminal Ca2+ influx and abundance of the key priming protein Munc13-1, a reduced rate of SV replenishment, as well as an altered topography of voltage-gated (CaV)2.1 Ca2+ channels, and fewer docked and membrane proximal synaptic vesicles (SVs). This hampers transmission of sound onset information likely affecting downstream neural computations such as of sound localization."}],"intvolume":"        41","publication":"Journal of Neuroscience","status":"public","has_accepted_license":"1","scopus_import":"1","ddc":["570"],"isi":1,"oa_version":"Published Version","date_updated":"2023-08-14T06:56:30Z","volume":41,"fulldoi":"https://doi.org/10.1523/JNEUROSCI.0586-21.2021","quality_controlled":"1","publication_identifier":{"eissn":["1529-2401"],"issn":["0270-6474"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"article_type":"original","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","month":"09","title":"RIM-binding protein 2 organizes Ca<sup>21</sup> channel topography and regulates release probability and vesicle replenishment at a fast central synapse","year":"2021","day":"15","publisher":"Society for Neuroscience","_id":"10051","acknowledgement":"This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) through the Collaborative Sensory Research Center 1286 [to C.W. (A4) and T.M. (B5)] and under Germany’s Excellence Strategy Grant EXC 2067/1-390729940. We thank S. Gerke, A.J. Goldak, and C. Senger-Freitag for expert technical assistance; G. Hoch for developing image analysis routines; and S. Chepurwar and N. Strenzke for technical support and discussion regarding in vivo experiments. We also thank Dr. Christian Rosenmund, Dr. Katharina Grauel, and Dr. Stephan Sigrist for providing RIM-BP2 KO mice and Dr. Masahiko Watanabe for providing the anti-neurexin-antibody, and Dr. Toshihisa Ohtsuka for the anti-ELKS-antibody. J. Neef for help with the STED imaging and image analysis; E. Neher and S. Rizzoli for discussion and comments on the manuscript; K. Eguchi for help with the statistical analysis; and C. H. Huang and J. Neef for constant support and scientific discussion.","doi":"10.1523/JNEUROSCI.0586-21.2021"},{"pmid":1,"abstract":[{"text":"Novelty facilitates formation of memories. The detection of novelty and storage of contextual memories are both mediated by the hippocampus, yet the mechanisms that link these two functions remain to be defined. Dentate granule cells (GCs) of the dorsal hippocampus fire upon novelty exposure forming engrams of contextual memory. However, their key excitatory inputs from the entorhinal cortex are not responsive to novelty and are insufficient to make dorsal GCs fire reliably. Here we uncover a powerful glutamatergic pathway to dorsal GCs from ventral hippocampal mossy cells (MCs) that relays novelty, and is necessary and sufficient for driving dorsal GCs activation. Furthermore, manipulation of ventral MCs activity bidirectionally regulates novelty-induced contextual memory acquisition. Our results show that ventral MCs activity controls memory formation through an intra-hippocampal interaction mechanism gated by novelty.","lang":"eng"}],"intvolume":"        31","date_published":"2021-01-11T00:00:00Z","department":[{"_id":"MaJö"},{"_id":"RySh"}],"external_id":{"pmid":["33065009"],"isi":["000614361000020"]},"language":[{"iso":"eng"}],"oa":1,"article_processing_charge":"No","ec_funded":1,"status":"public","publication":"Current Biology","ddc":["570"],"scopus_import":"1","has_accepted_license":"1","citation":{"apa":"Fredes Tolorza, F. A., Silva Sifuentes, M. A., Koppensteiner, P., Kobayashi, K., Jösch, M. A., &#38; Shigemoto, R. (2021). Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation. <i>Current Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cub.2020.09.074\">https://doi.org/10.1016/j.cub.2020.09.074</a>","short":"F.A. Fredes Tolorza, M.A. Silva Sifuentes, P. Koppensteiner, K. Kobayashi, M.A. Jösch, R. Shigemoto, Current Biology 31 (2021) P25–38.E5.","mla":"Fredes Tolorza, Felipe A., et al. “Ventro-Dorsal Hippocampal Pathway Gates Novelty-Induced Contextual Memory Formation.” <i>Current Biology</i>, vol. 31, no. 1, Elsevier, 2021, p. P25–38.E5, doi:<a href=\"https://doi.org/10.1016/j.cub.2020.09.074\">10.1016/j.cub.2020.09.074</a>.","chicago":"Fredes Tolorza, Felipe A, Maria A Silva Sifuentes, Peter Koppensteiner, Kenta Kobayashi, Maximilian A Jösch, and Ryuichi Shigemoto. “Ventro-Dorsal Hippocampal Pathway Gates Novelty-Induced Contextual Memory Formation.” <i>Current Biology</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.cub.2020.09.074\">https://doi.org/10.1016/j.cub.2020.09.074</a>.","ieee":"F. A. Fredes Tolorza, M. A. Silva Sifuentes, P. Koppensteiner, K. Kobayashi, M. A. Jösch, and R. Shigemoto, “Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation,” <i>Current Biology</i>, vol. 31, no. 1. Elsevier, p. P25–38.E5, 2021.","ama":"Fredes Tolorza FA, Silva Sifuentes MA, Koppensteiner P, Kobayashi K, Jösch MA, Shigemoto R. Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation. <i>Current Biology</i>. 2021;31(1):P25-38.E5. doi:<a href=\"https://doi.org/10.1016/j.cub.2020.09.074\">10.1016/j.cub.2020.09.074</a>","ista":"Fredes Tolorza FA, Silva Sifuentes MA, Koppensteiner P, Kobayashi K, Jösch MA, Shigemoto R. 2021. Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation. Current Biology. 31(1), P25–38.E5."},"file":[{"date_updated":"2020-10-19T13:31:28Z","date_created":"2020-10-19T13:31:28Z","relation":"main_file","file_id":"8678","checksum":"b7b9c8bc84a08befce365c675229a7d1","access_level":"open_access","success":1,"file_size":4915964,"creator":"dernst","file_name":"2021_CurrentBiology_Fredes.pdf","content_type":"application/pdf"}],"project":[{"grant_number":"694539","call_identifier":"H2020","_id":"25CA28EA-B435-11E9-9278-68D0E5697425","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour"}],"publication_status":"published","page":"P25-38.E5","date_created":"2020-02-28T10:56:18Z","type":"journal_article","author":[{"last_name":"Fredes Tolorza","id":"384825DA-F248-11E8-B48F-1D18A9856A87","full_name":"Fredes Tolorza, Felipe A","first_name":"Felipe A"},{"full_name":"Silva Sifuentes, Maria A","first_name":"Maria A","last_name":"Silva Sifuentes","id":"371B3D6E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Peter","full_name":"Koppensteiner, Peter","orcid":"0000-0002-3509-1948","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","last_name":"Koppensteiner"},{"full_name":"Kobayashi, Kenta","first_name":"Kenta","last_name":"Kobayashi"},{"last_name":"Jösch","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","full_name":"Jösch, Maximilian A","orcid":"0000-0002-3937-1330","first_name":"Maximilian A"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto","first_name":"Ryuichi","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi"}],"issue":"1","file_date_updated":"2020-10-19T13:31:28Z","tmp":{"short":"CC BY-NC-ND (4.0)","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)"},"month":"01","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_type":"original","day":"11","year":"2021","title":"Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation","doi":"10.1016/j.cub.2020.09.074","_id":"7551","publisher":"Elsevier","acknowledgement":"We thank Peter Jonas and Peter Somogyi for critically reading the manuscript, Satoshi Kida for helpful discussion, Taijia Makinen for providing the Prox1-creERT2 mouse line, and Hiromu Yawo for the VAMP2-Venus construct. We also thank Vivek Jayaraman, Ph.D.; Rex A. Kerr, Ph.D.; Douglas S. Kim, Ph.D.; Loren L. Looger, Ph.D.; and Karel Svoboda, Ph.D. from the GENIE Project, Janelia Farm Research Campus, Howard Hughes Medical Institute for the viral constructs used for GCaMP6s expression. We also thank Jacqueline Montanaro, Vanessa Zheden, David Kleindienst, and Laura Burnett for technical assistance, as well as Robert Beattie for imaging assistance. This work was supported by a European Research Council Advanced Grant 694539 to R.S.","related_material":{"link":[{"relation":"press_release","description":"News on IST Homepage","url":"https://ist.ac.at/en/news/remembering-novelty/"}]},"isi":1,"oa_version":"Published Version","volume":31,"date_updated":"2025-06-12T06:54:22Z","quality_controlled":"1","fulldoi":"https://doi.org/10.1016/j.cub.2020.09.074"},{"date_updated":"2026-09-13T22:31:04Z","volume":10,"fulldoi":"https://doi.org/10.7554/ELIFE.68274","quality_controlled":"1","publication_identifier":{"eissn":["2050-084X"]},"isi":1,"oa_version":"Published Version","title":"GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals","day":"29","year":"2021","doi":"10.7554/ELIFE.68274","_id":"9437","acknowledgement":"We are grateful to Akari Hagiwara and Toshihisa Ohtsuka for CAST antibody, and Masahiko Watanabe for neurexin antibody. We thank David Adams for kindly providing the stable Cav2.3 cell line. Cav2.3 KO mice were kindly provided by Tsutomu Tanabe. This project has received funding from the European Research Council (ERC) and European Commission (EC), under the European Union’s Horizon 2020 research and innovation programme (ERC grant agreement no. 694539 to Ryuichi Shigemoto, no. 692692 to Peter Jonas, and the Marie Skłodowska-Curie grant agreement no. 665385 to Cihan Önal), the Swiss National Science Foundation Grant 31003A-172881 to Bernhard Bettler and Deutsche Forschungsgemeinschaft (For 2143) and BIOSS-2 to Akos Kulik.","publisher":"eLife Sciences Publications","related_material":{"record":[{"id":"19271","relation":"dissertation_contains","status":"public"},{"status":"public","id":"9562","relation":"dissertation_contains"}],"link":[{"relation":"earlier_version","url":"https://doi.org/10.1101/2020.04.16.045112"}]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"article_type":"original","month":"04","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","type":"journal_article","author":[{"last_name":"Bhandari","id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0863-4481","full_name":"Bhandari, Pradeep","first_name":"Pradeep"},{"id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","last_name":"Vandael","first_name":"David H","orcid":"0000-0001-7577-1676","full_name":"Vandael, David H"},{"first_name":"Diego","full_name":"Fernández-Fernández, Diego","last_name":"Fernández-Fernández"},{"last_name":"Fritzius","full_name":"Fritzius, Thorsten","first_name":"Thorsten"},{"full_name":"Kleindienst, David","first_name":"David","last_name":"Kleindienst","id":"42E121A4-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Hüseyin C","orcid":"0000-0002-2771-2011","full_name":"Önal, Hüseyin C","id":"4659D740-F248-11E8-B48F-1D18A9856A87","last_name":"Önal"},{"last_name":"Montanaro-Punzengruber","id":"3786AB44-F248-11E8-B48F-1D18A9856A87","full_name":"Montanaro-Punzengruber, Jacqueline-Claire","first_name":"Jacqueline-Claire"},{"full_name":"Gassmann, Martin","first_name":"Martin","last_name":"Gassmann"},{"last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","first_name":"Peter M"},{"full_name":"Kulik, Akos","first_name":"Akos","last_name":"Kulik"},{"last_name":"Bettler","full_name":"Bettler, Bernhard","first_name":"Bernhard"},{"last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","first_name":"Ryuichi"},{"id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","last_name":"Koppensteiner","first_name":"Peter","orcid":"0000-0002-3509-1948","full_name":"Koppensteiner, Peter"}],"date_created":"2021-05-30T22:01:23Z","article_number":"e68274","file_date_updated":"2021-05-31T09:43:09Z","citation":{"short":"P. Bhandari, D.H. Vandael, D. Fernández-Fernández, T. Fritzius, D. Kleindienst, C. Önal, J.-C. Montanaro-Punzengruber, M. Gassmann, P.M. Jonas, A. Kulik, B. Bettler, R. Shigemoto, P. Koppensteiner, ELife 10 (2021).","apa":"Bhandari, P., Vandael, D. H., Fernández-Fernández, D., Fritzius, T., Kleindienst, D., Önal, C., … Koppensteiner, P. (2021). GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/ELIFE.68274\">https://doi.org/10.7554/ELIFE.68274</a>","mla":"Bhandari, Pradeep, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from Medial Habenula Terminals.” <i>ELife</i>, vol. 10, e68274, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/ELIFE.68274\">10.7554/ELIFE.68274</a>.","ama":"Bhandari P, Vandael DH, Fernández-Fernández D, et al. GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/ELIFE.68274\">10.7554/ELIFE.68274</a>","chicago":"Bhandari, Pradeep, David H Vandael, Diego Fernández-Fernández, Thorsten Fritzius, David Kleindienst, Cihan Önal, Jacqueline-Claire Montanaro-Punzengruber, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from Medial Habenula Terminals.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/ELIFE.68274\">https://doi.org/10.7554/ELIFE.68274</a>.","ieee":"P. Bhandari <i>et al.</i>, “GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","ista":"Bhandari P, Vandael DH, Fernández-Fernández D, Fritzius T, Kleindienst D, Önal C, Montanaro-Punzengruber J-C, Gassmann M, Jonas PM, Kulik A, Bettler B, Shigemoto R, Koppensteiner P. 2021. GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. eLife. 10, e68274."},"file":[{"content_type":"application/pdf","file_name":"2021_eLife_Bhandari.pdf","creator":"cziletti","file_size":8174719,"access_level":"open_access","success":1,"checksum":"6ebcb79999f889766f7cd79ee134ad28","file_id":"9440","relation":"main_file","date_created":"2021-05-31T09:43:09Z","date_updated":"2021-05-31T09:43:09Z"}],"publication_status":"published","project":[{"name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","_id":"25CA28EA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"694539"},{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"International IST Doctoral Program"}],"publication":"eLife","status":"public","ddc":["570"],"has_accepted_license":"1","scopus_import":"1","pmid":1,"language":[{"iso":"eng"}],"external_id":{"pmid":["33913808"],"isi":["000651761700001"]},"oa":1,"ec_funded":1,"article_processing_charge":"No","abstract":[{"text":"The synaptic connection from medial habenula (MHb) to interpeduncular nucleus (IPN) is critical for emotion-related behaviors and uniquely expresses R-type Ca2+ channels (Cav2.3) and auxiliary GABAB receptor (GBR) subunits, the K+-channel tetramerization domain-containing proteins (KCTDs). Activation of GBRs facilitates or inhibits transmitter release from MHb terminals depending on the IPN subnucleus, but the role of KCTDs is unknown. We therefore examined the localization and function of Cav2.3, GBRs, and KCTDs in this pathway in mice. We show in heterologous cells that KCTD8 and KCTD12b directly bind to Cav2.3 and that KCTD8 potentiates Cav2.3 currents in the absence of GBRs. In the rostral IPN, KCTD8, KCTD12b, and Cav2.3 co-localize at the presynaptic active zone. Genetic deletion indicated a bidirectional modulation of Cav2.3-mediated release by these KCTDs with a compensatory increase of KCTD8 in the active zone in KCTD12b-deficient mice. The interaction of Cav2.3 with KCTDs therefore scales synaptic strength independent of GBR activation.","lang":"eng"}],"intvolume":"        10","date_published":"2021-04-29T00:00:00Z","department":[{"_id":"RySh"},{"_id":"PeJo"}]},{"file":[{"creator":"dernst","file_size":2641297,"access_level":"open_access","file_name":"2019_JGP_Erdem.pdf","content_type":"application/pdf","file_id":"7450","checksum":"5706b4ccd74ee3e50bf7ecb2a203df71","date_created":"2020-02-05T07:20:32Z","relation":"main_file","date_updated":"2020-07-14T12:47:57Z"}],"citation":{"short":"F.A. Erdem, M. Ilic, P. Koppensteiner, J. Gołacki, G. Lubec, M. Freissmuth, W. Sandtner, The Journal of General Physiology 151 (2019) 1035–1050.","apa":"Erdem, F. A., Ilic, M., Koppensteiner, P., Gołacki, J., Lubec, G., Freissmuth, M., &#38; Sandtner, W. (2019). A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2. <i>The Journal of General Physiology</i>. Rockefeller University Press. <a href=\"https://doi.org/10.1085/jgp.201912318\">https://doi.org/10.1085/jgp.201912318</a>","ama":"Erdem FA, Ilic M, Koppensteiner P, et al. A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2. <i>The Journal of General Physiology</i>. 2019;151(8):1035-1050. doi:<a href=\"https://doi.org/10.1085/jgp.201912318\">10.1085/jgp.201912318</a>","mla":"Erdem, Fatma Asli, et al. “A Comparison of the Transport Kinetics of Glycine Transporter 1 and Glycine Transporter 2.” <i>The Journal of General Physiology</i>, vol. 151, no. 8, Rockefeller University Press, 2019, pp. 1035–50, doi:<a href=\"https://doi.org/10.1085/jgp.201912318\">10.1085/jgp.201912318</a>.","ieee":"F. A. Erdem <i>et al.</i>, “A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2,” <i>The Journal of General Physiology</i>, vol. 151, no. 8. Rockefeller University Press, pp. 1035–1050, 2019.","chicago":"Erdem, Fatma Asli, Marija Ilic, Peter Koppensteiner, Jakub Gołacki, Gert Lubec, Michael Freissmuth, and Walter Sandtner. “A Comparison of the Transport Kinetics of Glycine Transporter 1 and Glycine Transporter 2.” <i>The Journal of General Physiology</i>. Rockefeller University Press, 2019. <a href=\"https://doi.org/10.1085/jgp.201912318\">https://doi.org/10.1085/jgp.201912318</a>.","ista":"Erdem FA, Ilic M, Koppensteiner P, Gołacki J, Lubec G, Freissmuth M, Sandtner W. 2019. A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2. The Journal of General Physiology. 151(8), 1035–1050."},"publication_status":"published","author":[{"last_name":"Erdem","first_name":"Fatma Asli","full_name":"Erdem, Fatma Asli"},{"first_name":"Marija","full_name":"Ilic, Marija","last_name":"Ilic"},{"last_name":"Koppensteiner","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","full_name":"Koppensteiner, Peter","orcid":"0000-0002-3509-1948","first_name":"Peter"},{"first_name":"Jakub","full_name":"Gołacki, Jakub","last_name":"Gołacki"},{"first_name":"Gert","full_name":"Lubec, Gert","last_name":"Lubec"},{"first_name":"Michael","full_name":"Freissmuth, Michael","last_name":"Freissmuth"},{"last_name":"Sandtner","full_name":"Sandtner, Walter","first_name":"Walter"}],"issue":"8","type":"journal_article","date_created":"2020-01-29T16:06:29Z","page":"1035-1050","file_date_updated":"2020-07-14T12:47:57Z","pmid":1,"article_processing_charge":"No","language":[{"iso":"eng"}],"oa":1,"external_id":{"isi":["000478792500008"],"pmid":["31270129"]},"date_published":"2019-07-03T00:00:00Z","department":[{"_id":"RySh"}],"abstract":[{"lang":"eng","text":"Transporters of the solute carrier 6 (SLC6) family translocate their cognate substrate together with Na+ and Cl−. Detailed kinetic models exist for the transporters of GABA (GAT1/SLC6A1) and the monoamines dopamine (DAT/SLC6A3) and serotonin (SERT/SLC6A4). Here, we posited that the transport cycle of individual SLC6 transporters reflects the physiological requirements they operate under. We tested this hypothesis by analyzing the transport cycle of glycine transporter 1 (GlyT1/SLC6A9) and glycine transporter 2 (GlyT2/SLC6A5). GlyT2 is the only SLC6 family member known to translocate glycine, Na+, and Cl− in a 1:3:1 stoichiometry. We analyzed partial reactions in real time by electrophysiological recordings. Contrary to monoamine transporters, both GlyTs were found to have a high transport capacity driven by rapid return of the empty transporter after release of Cl− on the intracellular side. Rapid cycling of both GlyTs was further supported by highly cooperative binding of cosubstrate ions and substrate such that their forward transport mode was maintained even under conditions of elevated intracellular Na+ or Cl−. The most important differences in the transport cycle of GlyT1 and GlyT2 arose from the kinetics of charge movement and the resulting voltage-dependent rate-limiting reactions: the kinetics of GlyT1 were governed by transition of the substrate-bound transporter from outward- to inward-facing conformations, whereas the kinetics of GlyT2 were governed by Na+ binding (or a related conformational change). Kinetic modeling showed that the kinetics of GlyT1 are ideally suited for supplying the extracellular glycine levels required for NMDA receptor activation."}],"intvolume":"       151","publication":"The Journal of General Physiology","status":"public","scopus_import":"1","has_accepted_license":"1","ddc":["570"],"isi":1,"oa_version":"Published Version","date_updated":"2023-09-07T14:52:23Z","volume":151,"fulldoi":"https://doi.org/10.1085/jgp.201912318","quality_controlled":"1","publication_identifier":{"issn":["0022-1295"],"eissn":["1540-7748"]},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","short":"CC BY-NC-SA (4.0)","image":"/images/cc_by_nc_sa.png"},"article_type":"original","month":"07","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","title":"A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2","year":"2019","day":"03","publisher":"Rockefeller University Press","_id":"7398","doi":"10.1085/jgp.201912318"}]