---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '22295'
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.'
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
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).
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Lena A
  full_name: Schwarz, Lena A
  id: 29A8453C-F248-11E8-B48F-1D18A9856A87
  last_name: Schwarz
- first_name: Christoph
  full_name: Dotter, Christoph
  id: 4C66542E-F248-11E8-B48F-1D18A9856A87
  last_name: Dotter
  orcid: 0000-0002-9033-9096
- first_name: Sergey
  full_name: Isaev, Sergey
  last_name: Isaev
- first_name: Michela
  full_name: Lisi, Michela
  id: 39383c1b-d3eb-11ef-8d6c-c8cdf4e10c8c
  last_name: Lisi
- first_name: Daniel
  full_name: Malzl, Daniel
  last_name: Malzl
- first_name: Christoph
  full_name: Büschl, Christoph
  id: 2a8c054c-0913-11ee-9159-f8ef515809ed
  last_name: Büschl
- first_name: Sabrina
  full_name: Ladstätter, Sabrina
  last_name: Ladstätter
- first_name: Bárbara
  full_name: Oliveira, Bárbara
  id: 3B03AA1A-F248-11E8-B48F-1D18A9856A87
  last_name: Oliveira
- first_name: Matteo
  full_name: Barel, Matteo
  id: 8959927b-2236-11ed-bd6e-ea83d94ade0e
  last_name: Barel
- first_name: Bernadette
  full_name: Basilico, Bernadette
  id: 36035796-5ACA-11E9-A75E-7AF2E5697425
  last_name: Basilico
  orcid: 0000-0003-1843-3173
- first_name: Chaitanya
  full_name: Chintaluri, Chaitanya
  id: BA06AFEE-A4BA-11EA-AE5C-14673DDC885E
  last_name: Chintaluri
  orcid: 0000-0003-4252-1608
- first_name: Sarah
  full_name: Gorkiewicz, Sarah
  id: f141a35d-15a9-11ec-9fb2-fef6becc7b6f
  last_name: Gorkiewicz
- first_name: Mohammad
  full_name: Goudarzi, Mohammad
  id: 3384113A-F248-11E8-B48F-1D18A9856A87
  last_name: Goudarzi
- first_name: Tereza
  full_name: Belinova, Tereza
  id: 0bf89b6a-d28b-11eb-8bd6-f43768e4d368
  last_name: Belinova
- first_name: Stephan
  full_name: Reichl, Stephan
  last_name: Reichl
- first_name: Gintarė
  full_name: Sendžikaitė, Gintarė
  id: dd6d52f2-c50d-11eb-9548-bcf0ff82b344
  last_name: Sendžikaitė
- first_name: Satish
  full_name: Arcot Jayaram, Satish
  id: b0bbee33-09f7-11eb-909c-8b358058d28a
  last_name: Arcot Jayaram
  orcid: 0000-0002-2479-2669
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
  orcid: 0000-0002-3509-1948
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Tim P
  full_name: Vogels, Tim P
  id: CB6FF8D2-008F-11EA-8E08-2637E6697425
  last_name: Vogels
  orcid: 0000-0003-3295-6181
- first_name: Jörg
  full_name: Menche, Jörg
  last_name: Menche
- first_name: Igor
  full_name: Adameyko, Igor
  last_name: Adameyko
- first_name: Peter Vasili
  full_name: Kharchenko, Peter Vasili
  id: 0095641e-7eb7-11f1-8665-aec51a2ab5e0
  last_name: Kharchenko
- first_name: Christoph
  full_name: Bock, Christoph
  last_name: Bock
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
citation:
  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>
  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>
  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>.
  ieee: L. A. Schwarz <i>et al.</i>, “Cortical development dynamics across autism
    spectrum disorder mouse models,” <i>Nature</i>. Springer Nature, 2026.
  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.
  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>.
  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).
corr_author: '1'
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).
date_created: 2026-07-13T09:47:21Z
date_published: 2026-06-17T00:00:00Z
date_updated: 2026-08-04T09:29:55Z
day: '17'
ddc:
- '570'
department:
- _id: AnKi
- _id: GaNo
- _id: TiVo
- _id: ScienComp
- _id: GradSch
- _id: Bio
- _id: PreCl
doi: 10.1038/s41586-026-10679-1
external_id:
  pmid:
  - '42310454'
fulldoi: https://doi.org/10.1038/s41586-026-10679-1
has_accepted_license: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1038/s41586-026-10679-1
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 34ba8964-11ca-11ed-8bc3-e15864e7e9a6
  grant_number: '101044865'
  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
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232
  name: Molecular Drug Targets
- _id: ebb38b5d-77a9-11ec-83b8-a42e08120a88
  grant_number: FG1803 49015
  name: Neurobiology of anxiety in autism spectrum disorders
publication: Nature
publication_identifier:
  eissn:
  - 1476-4687
  issn:
  - 0028-0836
publication_status: epub_ahead
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - description: News on ISTA website
    relation: press_release
    url: https://ista.ac.at/en/news/patterns-in-genetic-chaos/
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Cortical development dynamics across autism spectrum disorder mouse models
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2026'
...
---
OA_place: publisher
OA_type: hybrid
_id: '19076'
abstract:
- lang: eng
  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.
acknowledged_ssus:
- _id: ScienComp
- _id: PreCl
- _id: LifeSc
- _id: Bio
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).
article_number: '7278'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Tomas A
  full_name: Vega Zuniga, Tomas A
  id: 2E7C4E78-F248-11E8-B48F-1D18A9856A87
  last_name: Vega Zuniga
- first_name: Anton L
  full_name: Sumser, Anton L
  id: 3320A096-F248-11E8-B48F-1D18A9856A87
  last_name: Sumser
  orcid: 0000-0002-4792-1881
- first_name: Olga
  full_name: Symonova, Olga
  id: 3C0C7BC6-F248-11E8-B48F-1D18A9856A87
  last_name: Symonova
  orcid: 0000-0003-2012-9947
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
  orcid: 0000-0002-3509-1948
- first_name: Florian
  full_name: Schmidt, Florian
  id: A2EF226A-AF19-11E9-924C-0525E6697425
  last_name: Schmidt
- first_name: Maximilian A
  full_name: Jösch, Maximilian A
  id: 2BD278E6-F248-11E8-B48F-1D18A9856A87
  last_name: Jösch
  orcid: 0000-0002-3937-1330
citation:
  ama: 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>
  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>
  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.
  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.
  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>.
  short: T.A. Vega Zuniga, A.L. Sumser, O. Symonova, P. Koppensteiner, F. Schmidt,
    M.A. Jösch, Nature Neuroscience 28 (2025).
corr_author: '1'
date_created: 2025-02-23T23:01:58Z
date_published: 2025-03-01T00:00:00Z
date_updated: 2026-06-18T18:12:08Z
day: '01'
ddc:
- '570'
department:
- _id: MaJö
- _id: PreCl
doi: 10.1038/s41593-025-01874-w
ec_funded: 1
external_id:
  isi:
  - '001416866800001'
  pmid:
  - '39930095'
fulldoi: https://doi.org/10.1038/s41593-025-01874-w
has_accepted_license: '1'
intvolume: '        28'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1038/s41593-025-01874-w
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2634E9D2-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '756502'
  name: Circuits of Visual Attention
- _id: bdaf81a8-d553-11ed-ba76-c95961984540
  grant_number: '101086580'
  name: 'Action Selection in the Midbrain: Neuromodulation of Visuomotor Senses'
- _id: 264FEA02-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 1098-2017
  name: Connecting sensory with motor processing in the superior colliculus
- _id: 266D407A-B435-11E9-9278-68D0E5697425
  grant_number: LT000256
  name: Neuronal networks of salience and spatial detection in the murine superior
    colliculus
publication: Nature Neuroscience
publication_identifier:
  eissn:
  - 1546-1726
  issn:
  - 1097-6256
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - description: News on ISTA Website
    relation: press_release
    url: https://ista.ac.at/en/news/high-tech-video-optimization-in-our-brain/
  record:
  - id: '18579'
    relation: research_data
    status: public
scopus_import: '1'
status: public
title: A thalamic hub-and-spoke network enables visual perception during action by
  coordinating visuomotor dynamics
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 28
year: '2025'
...
---
_id: '12875'
abstract:
- lang: eng
  text: The superior colliculus (SC) in the mammalian midbrain is essential for multisensory
    integration and is composed of a rich diversity of excitatory and inhibitory neurons
    and glia. However, the developmental principles directing the generation of SC
    cell-type diversity are not understood. Here, we pursued systematic cell lineage
    tracing in silico and in vivo, preserving full spatial information, using genetic
    mosaic analysis with double markers (MADM)-based clonal analysis with single-cell
    sequencing (MADM-CloneSeq). The analysis of clonally related cell lineages revealed
    that radial glial progenitors (RGPs) in SC are exceptionally multipotent. Individual
    resident RGPs have the capacity to produce all excitatory and inhibitory SC neuron
    types, even at the stage of terminal division. While individual clonal units show
    no pre-defined cellular composition, the establishment of appropriate relative
    proportions of distinct neuronal types occurs in a PTEN-dependent manner. Collectively,
    our findings provide an inaugural framework at the single-RGP/-cell level of the
    mammalian SC ontogeny.
acknowledged_ssus:
- _id: Bio
- _id: M-Shop
- _id: LifeSc
- _id: PreCl
acknowledgement: "We thank Liqun Luo for his continued support, for providing essential
  resources for generating Fzd10-CreER mice which were generated in his laboratory,
  and for comments on the manuscript; W. Zhong for providing Nestin-Cre transgenic
  mouse line for this study; A. Heger for mouse colony management; R. Beattie and
  T. Asenov for designing and producing components of acute slice recovery chamber
  for MADM-CloneSeq experiments; and K. Leopold, J. Rodarte and N. Amberg for initial
  experiments, technical support and/or assistance. This study was supported by the
  Scientific Service Units (SSU) of IST Austria through resources provided by the
  Imaging & Optics Facility (IOF), Laboratory Support Facility (LSF), Miba Machine
  Shop, and Pre-clinical Facility (PCF). G.C. received funding from European Commission
  (IST plus postdoctoral fellowship). This work was supported by ISTA institutional\r\nfunds;
  the Austrian Science Fund Special Research Programmes (FWF SFB F78 Neuro Stem Modulation)
  to S.H. "
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Giselle T
  full_name: Cheung, Giselle T
  id: 471195F6-F248-11E8-B48F-1D18A9856A87
  last_name: Cheung
  orcid: 0000-0001-8457-2572
- first_name: Florian
  full_name: Pauler, Florian
  id: 48EA0138-F248-11E8-B48F-1D18A9856A87
  last_name: Pauler
  orcid: 0000-0002-7462-0048
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
  orcid: 0000-0002-3509-1948
- first_name: Thomas
  full_name: Krausgruber, Thomas
  last_name: Krausgruber
- first_name: Carmen
  full_name: Streicher, Carmen
  id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
  last_name: Streicher
- first_name: Martin
  full_name: Schrammel, Martin
  id: f13e7cae-e8bd-11ed-841a-96dedf69f46d
  last_name: Schrammel
- first_name: Natalie Y
  full_name: Özgen, Natalie Y
  id: e68ece33-f6e0-11ea-865d-ae1031dcc090
  last_name: Özgen
- first_name: Alexis
  full_name: Ivec, Alexis
  id: 1d144691-e8be-11ed-9b33-bdd3077fad4c
  last_name: Ivec
- first_name: Christoph
  full_name: Bock, Christoph
  last_name: Bock
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
citation:
  ama: Cheung GT, Pauler F, Koppensteiner P, et al. Multipotent progenitors instruct
    ontogeny of the superior colliculus. <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>
  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>
  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>.
  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.
  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>.
  short: G.T. Cheung, F. Pauler, P. Koppensteiner, T. Krausgruber, C. Streicher, M.
    Schrammel, N.Y. Özgen, A. Ivec, C. Bock, R. Shigemoto, S. Hippenmeyer, Neuron
    112 (2024) 230–246.e11.
corr_author: '1'
date_created: 2023-04-27T09:41:48Z
date_published: 2024-01-17T00:00:00Z
date_updated: 2025-12-30T10:54:12Z
day: '17'
ddc:
- '570'
department:
- _id: SiHi
- _id: RySh
doi: 10.1016/j.neuron.2023.11.009
external_id:
  isi:
  - '001163937900001'
  pmid:
  - '38096816'
file:
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  date_updated: 2024-02-06T13:56:15Z
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  file_size: 5942467
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  success: 1
file_date_updated: 2024-02-06T13:56:15Z
fulldoi: https://doi.org/10.1016/j.neuron.2023.11.009
has_accepted_license: '1'
intvolume: '       112'
isi: 1
issue: '2'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: 230-246.e11
pmid: 1
project:
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
  grant_number: F7805
  name: Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular
    Mechanisms of Neural Stem Cell Lineage Progression
publication: Neuron
publication_identifier:
  issn:
  - 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  link:
  - description: News on ISTA Website
    relation: press_release
    url: https://ista.ac.at/en/news/the-pedigree-of-brain-cells/
scopus_import: '1'
status: public
title: Multipotent progenitors instruct ontogeny of the superior colliculus
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 112
year: '2024'
...
---
_id: '15385'
abstract:
- lang: eng
  text: "Relevant information about the data can be found in the 'Readme_Data.txt'
    file. \r\nA previous version of the publication can be found on BioRxiv: https://www.biorxiv.org/content/10.1101/2022.10.11.511691v4\r\nand
    published in Plos Biology (2024)"
acknowledged_ssus:
- _id: PreCl
- _id: M-Shop
- _id: LifeSc
- _id: Bio
acknowledgement: 'We thank Armel Nicolas, Bella Bruszel and Ewelina Dutkiewicz from
  the ISTA Mass Spectrometry Service (Lab Services Facilities) for all Proteomics
  work, including samples preparation, LC/MS data acquisition, searches and data evaluation.
  We thank Prof. Peter Jonas for his suggestion on the involvement of potassium channels
  and members of the Neuroethology group for their comments on the manuscript. Katalin
  Szigeti and Julie Murmann for experimental help. This research was supported by
  the Scientific Service Units of ISTA through resources provided by the Lab Support
  Facility, the Imaging and Optics Facility, the Machine Shop Unit and the Preclinical
  Facility, especially Freyja Langer and Michael Schunn. '
article_processing_charge: No
author:
- first_name: Laura
  full_name: Burnett, Laura
  id: 3B717F68-F248-11E8-B48F-1D18A9856A87
  last_name: Burnett
  orcid: 0000-0002-8937-410X
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
  orcid: 0000-0002-3509-1948
- first_name: Olga
  full_name: Symonova, Olga
  id: 3C0C7BC6-F248-11E8-B48F-1D18A9856A87
  last_name: Symonova
  orcid: 0000-0003-2012-9947
- first_name: Tomas
  full_name: Masson, Tomas
  id: 93ac43e8-8599-11eb-9b86-f6efb0a4c207
  last_name: Masson
  orcid: 0000-0002-2634-6283
- first_name: Tomas A
  full_name: Vega Zuniga, Tomas A
  id: 2E7C4E78-F248-11E8-B48F-1D18A9856A87
  last_name: Vega Zuniga
- first_name: Ximena
  full_name: Contreras, Ximena
  id: 475990FE-F248-11E8-B48F-1D18A9856A87
  last_name: Contreras
- first_name: Thomas
  full_name: Rülicke, Thomas
  last_name: Rülicke
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Maximilian A
  full_name: Jösch, Maximilian A
  id: 2BD278E6-F248-11E8-B48F-1D18A9856A87
  last_name: Jösch
  orcid: 0000-0002-3937-1330
citation:
  ama: Burnett L, Koppensteiner P, Symonova O, et al. Shared behavioural impairments
    in visual perception and place avoidance across different autism models are driven
    by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice. 2024.
    doi:<a href="https://doi.org/10.15479/AT:ISTA:15385">10.15479/AT:ISTA:15385</a>
  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>
  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>.
  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.
  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>.
  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>.
  short: L. Burnett, P. Koppensteiner, O. Symonova, T. Masson, T.A. Vega Zuniga, X.
    Contreras, T. Rülicke, R. Shigemoto, G. Novarino, M.A. Jösch, (2024).
corr_author: '1'
date_created: 2024-05-13T15:04:04Z
date_published: 2024-05-15T00:00:00Z
date_updated: 2025-09-08T07:57:11Z
day: '15'
ddc:
- '570'
department:
- _id: MaJö
- _id: PreCl
- _id: SiHi
- _id: RySh
- _id: GaNo
doi: 10.15479/AT:ISTA:15385
file:
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  creator: mjoesch
  date_created: 2024-05-15T06:09:17Z
  date_updated: 2024-05-15T06:09:17Z
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  date_created: 2024-05-15T06:09:12Z
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file_date_updated: 2024-05-16T09:08:20Z
fulldoi: https://doi.org/10.15479/AT:ISTA:15385
has_accepted_license: '1'
keyword:
- ASD
- periaqueductal gray
- perception
- behavior
- potassium channels
month: '05'
oa: 1
oa_version: Published Version
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '17142'
    relation: used_in_publication
    status: public
status: public
title: Shared behavioural impairments in visual perception and place avoidance across
  different autism models are driven by periaqueductal grey hypoexcitability in Setd5
  haploinsufficient mice
tmp:
  image: /images/cc_by_nc.png
  legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
  short: CC BY-NC (4.0)
type: research_data
user_id: 68b8ca59-c5b3-11ee-8790-cd641c68093d
year: '2024'
...
---
APC_amount: 6081,83 EUR
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '17142'
abstract:
- lang: eng
  text: Despite the diverse genetic origins of autism spectrum disorders (ASDs), affected
    individuals share strikingly similar and correlated behavioural traits that include
    perceptual and sensory processing challenges. Notably, the severity of these sensory
    symptoms is often predictive of the expression of other autistic traits. However,
    the origin of these perceptual deficits remains largely elusive. Here, we show
    a recurrent impairment in visual threat perception that is similarly impaired
    in 3 independent mouse models of ASD with different molecular aetiologies. Interestingly,
    this deficit is associated with reduced avoidance of threatening environments—a
    nonperceptual trait. Focusing on a common cause of ASDs, the Setd5 gene mutation,
    we define the molecular mechanism. We show that the perceptual impairment is caused
    by a potassium channel (Kv1)-mediated hypoexcitability in a subcortical node essential
    for the initiation of escape responses, the dorsal periaqueductal grey (dPAG).
    Targeted pharmacological Kv1 blockade rescued both perceptual and place avoidance
    deficits, causally linking seemingly unrelated trait deficits to the dPAG. Furthermore,
    we show that different molecular mechanisms converge on similar behavioural phenotypes
    by demonstrating that the autism models Cul3 and Ptchd1, despite having similar
    behavioural phenotypes, differ in their functional and molecular alteration. Our
    findings reveal a link between rapid perception controlled by subcortical pathways
    and appropriate learned interactions with the environment and define a nondevelopmental
    source of such deficits in ASD.
acknowledgement: 'This work was supported by a European Research Council Starting
  Grant 756502 (MJ). '
article_number: e3002668
article_processing_charge: Yes
article_type: original
author:
- first_name: Laura
  full_name: Burnett, Laura
  id: 3B717F68-F248-11E8-B48F-1D18A9856A87
  last_name: Burnett
  orcid: 0000-0002-8937-410X
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
  orcid: 0000-0002-3509-1948
- first_name: Olga
  full_name: Symonova, Olga
  id: 3C0C7BC6-F248-11E8-B48F-1D18A9856A87
  last_name: Symonova
  orcid: 0000-0003-2012-9947
- first_name: Tomas
  full_name: Masson, Tomas
  id: 93ac43e8-8599-11eb-9b86-f6efb0a4c207
  last_name: Masson
  orcid: 0000-0002-2634-6283
- first_name: Tomas A
  full_name: Vega Zuniga, Tomas A
  id: 2E7C4E78-F248-11E8-B48F-1D18A9856A87
  last_name: Vega Zuniga
- first_name: Ximena
  full_name: Contreras, Ximena
  id: 475990FE-F248-11E8-B48F-1D18A9856A87
  last_name: Contreras
- first_name: Thomas
  full_name: Rülicke, Thomas
  last_name: Rülicke
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Maximilian A
  full_name: Jösch, Maximilian A
  id: 2BD278E6-F248-11E8-B48F-1D18A9856A87
  last_name: Jösch
  orcid: 0000-0002-3937-1330
citation:
  ama: Burnett L, Koppensteiner P, Symonova O, et al. Shared behavioural impairments
    in visual perception and place avoidance across different autism models are driven
    by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice. <i>PLoS
    Biology</i>. 2024;22. doi:<a href="https://doi.org/10.1371/journal.pbio.3002668">10.1371/journal.pbio.3002668</a>
  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>
  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>.
  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.
  ista: Burnett L, Koppensteiner P, Symonova O, Masson T, Vega Zuniga TA, Contreras
    X, Rülicke T, Shigemoto R, Novarino G, Jösch MA. 2024. Shared behavioural impairments
    in visual perception and place avoidance across different autism models are driven
    by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice. PLoS
    Biology. 22, e3002668.
  mla: Burnett, Laura, et al. “Shared Behavioural Impairments in Visual Perception
    and Place Avoidance across Different Autism Models Are Driven by Periaqueductal
    Grey Hypoexcitability in Setd5 Haploinsufficient Mice.” <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>.
  short: L. Burnett, P. Koppensteiner, O. Symonova, T. Masson, T.A. Vega Zuniga, X.
    Contreras, T. Rülicke, R. Shigemoto, G. Novarino, M.A. Jösch, PLoS Biology 22
    (2024).
corr_author: '1'
date_created: 2024-06-16T22:01:05Z
date_published: 2024-06-10T00:00:00Z
date_updated: 2025-09-08T07:57:11Z
day: '10'
ddc:
- '570'
department:
- _id: RySh
- _id: GaNo
- _id: MaJö
doi: 10.1371/journal.pbio.3002668
ec_funded: 1
external_id:
  isi:
  - '001246176800003'
  pmid:
  - '38857283'
file:
- access_level: open_access
  checksum: 496e1aa4fd5b92b7e4087ecc2c964133
  content_type: application/pdf
  creator: dernst
  date_created: 2025-01-09T10:39:41Z
  date_updated: 2025-01-09T10:39:41Z
  file_id: '18805'
  file_name: 2024_PloS_Burnett.pdf
  file_size: 4016568
  relation: main_file
  success: 1
file_date_updated: 2025-01-09T10:39:41Z
fulldoi: https://doi.org/10.1371/journal.pbio.3002668
has_accepted_license: '1'
intvolume: '        22'
isi: 1
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2634E9D2-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '756502'
  name: Circuits of Visual Attention
publication: PLoS Biology
publication_identifier:
  eissn:
  - 1545-7885
  issn:
  - 1544-9173
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
related_material:
  link:
  - relation: software
    url: https://doi.org/10.5281/zenodo.11130587
  record:
  - id: '15385'
    relation: research_data
    status: public
scopus_import: '1'
status: public
title: Shared behavioural impairments in visual perception and place avoidance across
  different autism models are driven by periaqueductal grey hypoexcitability in Setd5
  haploinsufficient mice
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 22
year: '2024'
...
---
OA_place: publisher
_id: '18579'
abstract:
- lang: eng
  text: 'Electrophysiological, calcium two-photon recordings and behavioral data for
    Vega-Zuniga et al.  Relevant information can be found in the ''README.txt'' files. '
acknowledged_ssus:
- _id: ScienComp
- _id: PreCl
- _id: M-Shop
- _id: Bio
- _id: LifeSc
acknowledgement: Freyja Lange, Michael Schunn, and Todor Asenov
article_processing_charge: No
author:
- first_name: Tomas A
  full_name: Vega Zuniga, Tomas A
  id: 2E7C4E78-F248-11E8-B48F-1D18A9856A87
  last_name: Vega Zuniga
- first_name: Anton L
  full_name: Sumser, Anton L
  id: 3320A096-F248-11E8-B48F-1D18A9856A87
  last_name: Sumser
  orcid: 0000-0002-4792-1881
- first_name: Olga
  full_name: Symonova, Olga
  id: 3C0C7BC6-F248-11E8-B48F-1D18A9856A87
  last_name: Symonova
  orcid: 0000-0003-2012-9947
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
  orcid: 0000-0002-3509-1948
- first_name: Florian
  full_name: Schmidt, Florian
  id: A2EF226A-AF19-11E9-924C-0525E6697425
  last_name: Schmidt
- first_name: Maximilian A
  full_name: Jösch, Maximilian A
  id: 2BD278E6-F248-11E8-B48F-1D18A9856A87
  last_name: Jösch
  orcid: 0000-0002-3937-1330
citation:
  ama: 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>
  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>
  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>.
  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.
  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>.
  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>.
  short: T.A. Vega Zuniga, A.L. Sumser, O. Symonova, P. Koppensteiner, F. Schmidt,
    M.A. Jösch, (2024).
corr_author: '1'
date_created: 2024-11-22T13:48:12Z
date_published: 2024-12-09T00:00:00Z
date_updated: 2026-06-18T18:12:08Z
day: '09'
ddc:
- '570'
department:
- _id: MaJö
doi: 10.15479/AT:ISTA:18579
ec_funded: 1
file:
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file_date_updated: 2024-12-09T12:54:55Z
fulldoi: https://doi.org/10.15479/AT:ISTA:18579
has_accepted_license: '1'
month: '12'
oa: 1
oa_version: Published Version
project:
- _id: 264FEA02-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 1098-2017
  name: Connecting sensory with motor processing in the superior colliculus
- _id: 266D407A-B435-11E9-9278-68D0E5697425
  grant_number: LT000256
  name: Neuronal networks of salience and spatial detection in the murine superior
    colliculus
- _id: 2634E9D2-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '756502'
  name: Circuits of Visual Attention
- _id: bdaf81a8-d553-11ed-ba76-c95961984540
  grant_number: '101086580'
  name: 'Action Selection in the Midbrain: Neuromodulation of Visuomotor Senses'
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '19076'
    relation: used_in_publication
    status: public
status: public
title: A thalamic hub-and-spoke network enables visual perception during action by
  coordinating visuomotor dynamics
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2024'
...
---
APC_amount: 804 EUR
OA_place: publisher
OA_type: gold
_id: '17232'
abstract:
- lang: eng
  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"
acknowledged_ssus:
- _id: Bio
- _id: M-Shop
- _id: PreCl
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).
article_number: '103168'
article_processing_charge: Yes
article_type: original
author:
- first_name: Giselle T
  full_name: Cheung, Giselle T
  id: 471195F6-F248-11E8-B48F-1D18A9856A87
  last_name: Cheung
  orcid: 0000-0001-8457-2572
- first_name: Florian
  full_name: Pauler, Florian
  id: 48EA0138-F248-11E8-B48F-1D18A9856A87
  last_name: Pauler
  orcid: 0000-0002-7462-0048
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
  orcid: 0000-0002-3509-1948
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
citation:
  ama: Cheung GT, Pauler F, Koppensteiner P, 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>
  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>
  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.
  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>.
  short: G.T. Cheung, F. Pauler, P. Koppensteiner, S. Hippenmeyer, STAR Protocols
    5 (2024).
corr_author: '1'
date_created: 2024-07-14T22:01:10Z
date_published: 2024-09-20T00:00:00Z
date_updated: 2025-12-30T10:54:12Z
day: '20'
ddc:
- '570'
department:
- _id: SiHi
- _id: PreCl
doi: 10.1016/j.xpro.2024.103168
external_id:
  pmid:
  - '38968076'
file:
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  checksum: 464f52ecc6ec92f509552823bb82bf79
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  creator: dernst
  date_created: 2025-01-09T12:16:53Z
  date_updated: 2025-01-09T12:16:53Z
  file_id: '18810'
  file_name: 2024_STARProtoc_Cheung2.pdf
  file_size: 6445556
  relation: main_file
  success: 1
file_date_updated: 2025-01-09T12:16:53Z
fulldoi: https://doi.org/10.1016/j.xpro.2024.103168
has_accepted_license: '1'
intvolume: '         5'
issue: '3'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
  grant_number: F7805
  name: Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular
    Mechanisms of Neural Stem Cell Lineage Progression
publication: STAR Protocols
publication_identifier:
  eissn:
  - 2666-1667
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Protocol for mapping cell lineage and cell-type identity of clonally-related
  cells in situ using MADM-CloneSeq
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 5
year: '2024'
...
---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '17280'
abstract:
- lang: eng
  text: Adherens junction–associated protein 1 (AJAP1) has been implicated in brain
    diseases; however, a pathogenic mechanism has not been identified. AJAP1 is widely
    expressed in neurons and binds to γ-aminobutyric acid type B receptors (GBRs),
    which inhibit neurotransmitter release at most synapses in the brain. Here, we
    show that AJAP1 is selectively expressed in dendrites and trans-synaptically recruits
    GBRs to presynaptic sites of neurons expressing AJAP1. We have identified several
    monoallelic AJAP1 variants in individuals with epilepsy and/or neurodevelopmental
    disorders. Specifically, we show that the variant p.(W183C) lacks binding to GBRs,
    resulting in the inability to recruit them. Ultrastructural analysis revealed
    significantly decreased presynaptic GBR levels in Ajap1−/− and Ajap1W183C/+ mice.
    Consequently, these mice exhibited reduced GBR-mediated presynaptic inhibition
    at excitatory and inhibitory synapses, along with impaired synaptic plasticity.
    Our study reveals that AJAP1 enables the postsynaptic neuron to regulate the level
    of presynaptic GBR-mediated inhibition, supporting the clinical relevance of loss-of-function
    AJAP1 variants.
acknowledgement: "Ajap1HA/HA and Ajap1W183C/+ mice were generated in collaboration
  with Pawel Pelczar at the center for transgenic models at the University of Basel,
  Switzerland. We thank the imaging core facility (IMCF, University of Basel) and
  in particular A. Ferrand for the technical assistance provided on the OMX 3D-SIM
  microscope.\r\nThis work was supported by a grant from the Swiss National Science
  Foundation (SNF) to B.B. (31003A-152970, 310030B-201291), an NIH grant to E.A. and
  E.H.S. (R01NS058721), DFG grants to B.F. (TRR 152 project ID 239283807, FA 332/15-1,
  16-1), and grants to P.S. from AIMS-2-TRIALS, which are supported by the Innovative
  Medicines Initiatives from the European Commission joint undertaking under grant
  agreement No 777394."
article_number: adk5462
article_processing_charge: Yes
article_type: original
author:
- first_name: Simon
  full_name: Früh, Simon
  last_name: Früh
- first_name: Sami
  full_name: Boudkkazi, Sami
  last_name: Boudkkazi
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
  orcid: 0000-0002-3509-1948
- first_name: Vita
  full_name: Sereikaite, Vita
  last_name: Sereikaite
- first_name: Li Yuan
  full_name: Chen, Li Yuan
  last_name: Chen
- first_name: Diego
  full_name: Fernandez-Fernandez, Diego
  last_name: Fernandez-Fernandez
- first_name: Pascal D.
  full_name: Rem, Pascal D.
  last_name: Rem
- first_name: Daniel
  full_name: Ulrich, Daniel
  last_name: Ulrich
- first_name: Jochen
  full_name: Schwenk, Jochen
  last_name: Schwenk
- first_name: Ziyang
  full_name: Chen, Ziyang
  last_name: Chen
- first_name: Elodie Le
  full_name: Monnier, Elodie Le
  last_name: Monnier
- first_name: Thorsten
  full_name: Fritzius, Thorsten
  last_name: Fritzius
- first_name: Sabrina M.
  full_name: Innocenti, Sabrina M.
  last_name: Innocenti
- first_name: Valérie
  full_name: Besseyrias, Valérie
  last_name: Besseyrias
- first_name: Luca
  full_name: Trovò, Luca
  last_name: Trovò
- first_name: Michal
  full_name: Stawarski, Michal
  last_name: Stawarski
- first_name: Emanuela
  full_name: Argilli, Emanuela
  last_name: Argilli
- first_name: Elliott H.
  full_name: Sherr, Elliott H.
  last_name: Sherr
- first_name: Bregje
  full_name: Van Bon, Bregje
  last_name: Van Bon
- first_name: Erik Jan
  full_name: Kamsteeg, Erik Jan
  last_name: Kamsteeg
- first_name: Maria
  full_name: Iascone, Maria
  last_name: Iascone
- first_name: Alba
  full_name: Pilotta, Alba
  last_name: Pilotta
- first_name: Maria R.
  full_name: Cutrì, Maria R.
  last_name: Cutrì
- first_name: Mahshid S.
  full_name: Azamian, Mahshid S.
  last_name: Azamian
- first_name: Andrés
  full_name: Hernández-García, Andrés
  last_name: Hernández-García
- first_name: Seema R.
  full_name: Lalani, Seema R.
  last_name: Lalani
- first_name: Jill A.
  full_name: Rosenfeld, Jill A.
  last_name: Rosenfeld
- first_name: Xiaonan
  full_name: Zhao, Xiaonan
  last_name: Zhao
- first_name: Tiphanie P.
  full_name: Vogel, Tiphanie P.
  last_name: Vogel
- first_name: Herda
  full_name: Ona, Herda
  last_name: Ona
- first_name: Daryl A.
  full_name: Scott, Daryl A.
  last_name: Scott
- first_name: Peter
  full_name: Scheiffele, Peter
  last_name: Scheiffele
- first_name: Kristian
  full_name: Strømgaard, Kristian
  last_name: Strømgaard
- first_name: Mehdi
  full_name: Tafti, Mehdi
  last_name: Tafti
- first_name: Martin
  full_name: Gassmann, Martin
  last_name: Gassmann
- first_name: Bernd
  full_name: Fakler, Bernd
  last_name: Fakler
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
- first_name: Bernhard
  full_name: Bettler, Bernhard
  last_name: Bettler
citation:
  ama: Früh S, Boudkkazi S, Koppensteiner P, et al. Monoallelic de novo AJAP1 loss-of-
    function variants disrupt trans-synaptic control of neurotransmitter release.
    <i>Science Advances</i>. 2024;10(28). doi:<a href="https://doi.org/10.1126/sciadv.adk5462">10.1126/sciadv.adk5462</a>
  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>
  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>.
  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.
  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>.
  short: S. Früh, S. Boudkkazi, P. Koppensteiner, V. Sereikaite, L.Y. Chen, D. Fernandez-Fernandez,
    P.D. Rem, D. Ulrich, J. Schwenk, Z. Chen, E.L. Monnier, T. Fritzius, S.M. Innocenti,
    V. Besseyrias, L. Trovò, M. Stawarski, E. Argilli, E.H. Sherr, B. Van Bon, E.J.
    Kamsteeg, M. Iascone, A. Pilotta, M.R. Cutrì, M.S. Azamian, A. Hernández-García,
    S.R. Lalani, J.A. Rosenfeld, X. Zhao, T.P. Vogel, H. Ona, D.A. Scott, P. Scheiffele,
    K. Strømgaard, M. Tafti, M. Gassmann, B. Fakler, R. Shigemoto, B. Bettler, Science
    Advances 10 (2024).
date_created: 2024-07-21T22:01:01Z
date_published: 2024-07-12T00:00:00Z
date_updated: 2025-09-08T08:15:54Z
day: '12'
ddc:
- '570'
department:
- _id: RySh
- _id: PreCl
doi: 10.1126/sciadv.adk5462
external_id:
  isi:
  - '001280159000022'
  pmid:
  - '38985877'
file:
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  checksum: 9cbc4501fcd4ba1c0811fd244031422b
  content_type: application/pdf
  creator: dernst
  date_created: 2024-07-22T06:29:27Z
  date_updated: 2024-07-22T06:29:27Z
  file_id: '17287'
  file_name: 2024_ScienceAdv_Früh.pdf
  file_size: 7241489
  relation: main_file
  success: 1
file_date_updated: 2024-07-22T06:29:27Z
fulldoi: https://doi.org/10.1126/sciadv.adk5462
has_accepted_license: '1'
intvolume: '        10'
isi: 1
issue: '28'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
publication: Science Advances
publication_identifier:
  eissn:
  - 2375-2548
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
scopus_import: '1'
status: public
title: Monoallelic de novo AJAP1 loss-of- function variants disrupt trans-synaptic
  control of neurotransmitter release
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 10
year: '2024'
...
---
APC_amount: 5887,8 EUR
OA_place: publisher
OA_type: hybrid
_id: '15084'
abstract:
- lang: eng
  text: "GABAB receptor (GBR) activation inhibits neurotransmitter release in axon
    terminals in the brain, except in medial habenula (MHb) terminals, which show
    robust potentiation. However, mechanisms underlying this enigmatic potentiation
    remain elusive. Here, we report that GBR activation on MHb terminals induces an
    activity-dependent transition from a facilitating, tonic to a depressing, phasic
    neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase
    in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked
    synaptic vesicles (SVs) at the presynaptic active zone (AZ). Strikingly, the depressing
    phasic release exhibits looser coupling distance than the tonic release. Furthermore,
    the tonic and phasic release are selectively affected by deletion of synaptoporin
    (SPO) and Ca\r\n            <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."
acknowledged_ssus:
- _id: M-Shop
- _id: PreCl
- _id: EM-Fac
acknowledgement: We thank Erwin Neher and Ipe Ninan for critical comments on the manuscript.
  This project has received funding from the European Research Council (ERC) and European
  Commission, under the European Union’s Horizon 2020 research and innovation program
  (ERC grant agreement no. 694539 to R.S. and the Marie Skłodowska-Curie grant agreement
  no. 665385 to C.Ö.). This study was supported by the Cooperative Study Program of
  Center for Animal Resources and Collaborative Study of NINS. We thank Kohgaku Eguchi
  for statistical analysis, Yu Kasugai for additional EM imaging, Robert Beattie for
  the design of the slice recovery chamber for Flash and Freeze experiments, Todor
  Asenov from the ISTA machine shop for custom part preparations for high-pressure
  freezing, the ISTA preclinical facility for animal caretaking, and the ISTA EM facilities
  for technical support.
article_number: e2301449121
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
  orcid: 0000-0002-3509-1948
- first_name: Pradeep
  full_name: Bhandari, Pradeep
  id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87
  last_name: Bhandari
  orcid: 0000-0003-0863-4481
- first_name: Hüseyin C
  full_name: Önal, Hüseyin C
  id: 4659D740-F248-11E8-B48F-1D18A9856A87
  last_name: Önal
  orcid: 0000-0002-2771-2011
- first_name: Carolina
  full_name: Borges Merjane, Carolina
  id: 4305C450-F248-11E8-B48F-1D18A9856A87
  last_name: Borges Merjane
  orcid: 0000-0003-0005-401X
- first_name: Elodie
  full_name: Le Monnier, Elodie
  id: 3B59276A-F248-11E8-B48F-1D18A9856A87
  last_name: Le Monnier
- first_name: Utsa
  full_name: Roy, Utsa
  id: 4d26cf11-5355-11ee-ae5a-eb05e255b9b2
  last_name: Roy
- first_name: Yukihiro
  full_name: Nakamura, Yukihiro
  last_name: Nakamura
- first_name: Tetsushi
  full_name: Sadakata, Tetsushi
  last_name: Sadakata
- first_name: Makoto
  full_name: Sanbo, Makoto
  last_name: Sanbo
- first_name: Masumi
  full_name: Hirabayashi, Masumi
  last_name: Hirabayashi
- first_name: JeongSeop
  full_name: Rhee, JeongSeop
  last_name: Rhee
- first_name: Nils
  full_name: Brose, Nils
  last_name: Brose
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
citation:
  ama: Koppensteiner P, Bhandari P, Önal C, et al. GABAB receptors induce phasic release
    from medial habenula terminals through activity-dependent recruitment of release-ready
    vesicles. <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>
  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>
  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>.
  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.
  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>.
  short: P. Koppensteiner, P. Bhandari, C. Önal, C. Borges Merjane, E. Le Monnier,
    U. Roy, Y. Nakamura, T. Sadakata, M. Sanbo, M. Hirabayashi, J. Rhee, N. Brose,
    P.M. Jonas, R. Shigemoto, Proceedings of the National Academy of Sciences of the
    United States of America 121 (2024).
corr_author: '1'
date_created: 2024-03-05T09:23:55Z
date_published: 2024-02-20T00:00:00Z
date_updated: 2026-09-13T22:30:36Z
day: '20'
ddc:
- '570'
department:
- _id: RySh
- _id: PeJo
doi: 10.1073/pnas.2301449121
ec_funded: 1
external_id:
  isi:
  - '001208567300006'
  pmid:
  - '38346189'
file:
- access_level: open_access
  checksum: b25b2a057c266ff317a48b0d54d6fc8a
  content_type: application/pdf
  creator: dernst
  date_created: 2024-03-12T13:42:42Z
  date_updated: 2024-03-12T13:42:42Z
  file_id: '15110'
  file_name: 2024_PNAS_Koppensteiner.pdf
  file_size: 13648221
  relation: main_file
  success: 1
file_date_updated: 2024-03-12T13:42:42Z
fulldoi: https://doi.org/10.1073/pnas.2301449121
has_accepted_license: '1'
intvolume: '       121'
isi: 1
issue: '8'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25CA28EA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '694539'
  name: 'In situ analysis of single channel subunit composition in neurons: physiological
    implication in synaptic plasticity and behaviour'
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
publication: Proceedings of the National Academy of Sciences of the United States
  of America
publication_identifier:
  eissn:
  - 1091-6490
  issn:
  - 0027-8424
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
  link:
  - description: News on ISTA Website
    relation: press_release
    url: https://ista.ac.at/en/news/neuronal-insights-flash-and-freeze-fracture/
  record:
  - id: '13173'
    relation: research_data
    status: public
  - id: '19271'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: GABAB receptors induce phasic release from medial habenula terminals through
  activity-dependent recruitment of release-ready vesicles
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 121
year: '2024'
...
---
_id: '10051'
abstract:
- lang: eng
  text: 'Rab-interacting molecule (RIM)-binding protein 2 (BP2) is a multidomain protein
    of the presynaptic active zone (AZ). By binding to RIM, bassoon (Bsn), and voltage-gated
    Ca2+ channels (CaV), it is considered to be a central organizer of the topography
    of CaV and release sites of synaptic vesicles (SVs) at the AZ. Here, we used RIM-BP2
    knock-out (KO) mice and their wild-type (WT) littermates of either sex to investigate
    the role of RIM-BP2 at the endbulb of Held synapse of auditory nerve fibers (ANFs)
    with bushy cells (BCs) of the cochlear nucleus, a fast relay of the auditory pathway
    with high release probability. Disruption of RIM-BP2 lowered release probability
    altering short-term plasticity and reduced evoked EPSCs. Analysis of SV pool dynamics
    during high-frequency train stimulation indicated a reduction of SVs with high
    release probability but an overall normal size of the readily releasable SV pool
    (RRP). The Ca2+-dependent fast component of SV replenishment after RRP depletion
    was slowed. Ultrastructural analysis by superresolution light and electron microscopy
    revealed an impaired topography of presynaptic CaV and a reduction of docked and
    membrane-proximal SVs at the AZ. We conclude that RIM-BP2 organizes the topography
    of CaV, and promotes SV tethering and docking. This way RIM-BP2 is critical for
    establishing a high initial release probability as required to reliably signal
    sound onset information that we found to be degraded in BCs of RIM-BP2-deficient
    mice in vivo. SIGNIFICANCE STATEMENT: Rab-interacting molecule (RIM)-binding proteins
    (BPs) are key organizers of the active zone (AZ). Using a multidisciplinary approach
    to the calyceal endbulb of Held synapse that transmits auditory information at
    rates of up to hundreds of Hertz with submillisecond precision we demonstrate
    a requirement for RIM-BP2 for normal auditory signaling. Endbulb synapses lacking
    RIM-BP2 show a reduced release probability despite normal whole-terminal Ca2+
    influx and abundance of the key priming protein Munc13-1, a reduced rate of SV
    replenishment, as well as an altered topography of voltage-gated (CaV)2.1 Ca2+
    channels, and fewer docked and membrane proximal synaptic vesicles (SVs). This
    hampers transmission of sound onset information likely affecting downstream neural
    computations such as of sound localization.'
acknowledgement: This work was supported by the Deutsche Forschungsgemeinschaft (DFG,
  German Research Foundation) through the Collaborative Sensory Research Center 1286
  [to C.W. (A4) and T.M. (B5)] and under Germany’s Excellence Strategy Grant EXC 2067/1-390729940.
  We thank S. Gerke, A.J. Goldak, and C. Senger-Freitag for expert technical assistance;
  G. Hoch for developing image analysis routines; and S. Chepurwar and N. Strenzke
  for technical support and discussion regarding in vivo experiments. We also thank
  Dr. Christian Rosenmund, Dr. Katharina Grauel, and Dr. Stephan Sigrist for providing
  RIM-BP2 KO mice and Dr. Masahiko Watanabe for providing the anti-neurexin-antibody,
  and Dr. Toshihisa Ohtsuka for the anti-ELKS-antibody. J. Neef for help with the
  STED imaging and image analysis; E. Neher and S. Rizzoli for discussion and comments
  on the manuscript; K. Eguchi for help with the statistical analysis; and C. H. Huang
  and J. Neef for constant support and scientific discussion.
article_processing_charge: No
article_type: original
author:
- first_name: Tanvi
  full_name: Butola, Tanvi
  last_name: Butola
- first_name: Theocharis
  full_name: Alvanos, Theocharis
  last_name: Alvanos
- first_name: Anika
  full_name: Hintze, Anika
  last_name: Hintze
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
  orcid: 0000-0002-3509-1948
- first_name: David
  full_name: Kleindienst, David
  id: 42E121A4-F248-11E8-B48F-1D18A9856A87
  last_name: Kleindienst
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
- first_name: Carolin
  full_name: Wichmann, Carolin
  last_name: Wichmann
- first_name: Tobias
  full_name: Moser, Tobias
  last_name: Moser
citation:
  ama: Butola T, Alvanos T, Hintze A, et al. RIM-binding protein 2 organizes 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>
  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>
  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.
  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>.
  short: T. Butola, T. Alvanos, A. Hintze, P. Koppensteiner, D. Kleindienst, R. Shigemoto,
    C. Wichmann, T. Moser, Journal of Neuroscience 41 (2021) 7742–7767.
date_created: 2021-09-27T14:33:13Z
date_published: 2021-09-15T00:00:00Z
date_updated: 2023-08-14T06:56:30Z
day: '15'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1523/JNEUROSCI.0586-21.2021
external_id:
  isi:
  - '000752287700005'
  pmid:
  - '34353898'
file:
- access_level: open_access
  checksum: 769ab627c7355a50ccfd445e43a5f351
  content_type: application/pdf
  creator: dernst
  date_created: 2022-05-31T09:10:15Z
  date_updated: 2022-05-31T09:10:15Z
  file_id: '11423'
  file_name: 2021_JourNeuroscience_Butola.pdf
  file_size: 11571961
  relation: main_file
  success: 1
file_date_updated: 2022-05-31T09:10:15Z
fulldoi: https://doi.org/10.1523/JNEUROSCI.0586-21.2021
has_accepted_license: '1'
intvolume: '        41'
isi: 1
issue: '37'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: 7742-7767
pmid: 1
publication: Journal of Neuroscience
publication_identifier:
  eissn:
  - 1529-2401
  issn:
  - 0270-6474
publication_status: published
publisher: Society for Neuroscience
quality_controlled: '1'
scopus_import: '1'
status: public
title: RIM-binding protein 2 organizes Ca<sup>21</sup> channel topography and regulates
  release probability and vesicle replenishment at a fast central synapse
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 41
year: '2021'
...
---
_id: '7551'
abstract:
- lang: eng
  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.
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.
article_processing_charge: No
article_type: original
author:
- first_name: Felipe A
  full_name: Fredes Tolorza, Felipe A
  id: 384825DA-F248-11E8-B48F-1D18A9856A87
  last_name: Fredes Tolorza
- first_name: Maria A
  full_name: Silva Sifuentes, Maria A
  id: 371B3D6E-F248-11E8-B48F-1D18A9856A87
  last_name: Silva Sifuentes
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
  orcid: 0000-0002-3509-1948
- first_name: Kenta
  full_name: Kobayashi, Kenta
  last_name: Kobayashi
- first_name: Maximilian A
  full_name: Jösch, Maximilian A
  id: 2BD278E6-F248-11E8-B48F-1D18A9856A87
  last_name: Jösch
  orcid: 0000-0002-3937-1330
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
citation:
  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>
  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>
  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.
  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.
  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>.
  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.
date_created: 2020-02-28T10:56:18Z
date_published: 2021-01-11T00:00:00Z
date_updated: 2025-06-12T06:54:22Z
day: '11'
ddc:
- '570'
department:
- _id: MaJö
- _id: RySh
doi: 10.1016/j.cub.2020.09.074
ec_funded: 1
external_id:
  isi:
  - '000614361000020'
  pmid:
  - '33065009'
file:
- access_level: open_access
  checksum: b7b9c8bc84a08befce365c675229a7d1
  content_type: application/pdf
  creator: dernst
  date_created: 2020-10-19T13:31:28Z
  date_updated: 2020-10-19T13:31:28Z
  file_id: '8678'
  file_name: 2021_CurrentBiology_Fredes.pdf
  file_size: 4915964
  relation: main_file
  success: 1
file_date_updated: 2020-10-19T13:31:28Z
fulldoi: https://doi.org/10.1016/j.cub.2020.09.074
has_accepted_license: '1'
intvolume: '        31'
isi: 1
issue: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: P25-38.E5
pmid: 1
project:
- _id: 25CA28EA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '694539'
  name: 'In situ analysis of single channel subunit composition in neurons: physiological
    implication in synaptic plasticity and behaviour'
publication: Current Biology
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/remembering-novelty/
scopus_import: '1'
status: public
title: Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 31
year: '2021'
...
---
_id: '9437'
abstract:
- lang: eng
  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.
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.
article_number: e68274
article_processing_charge: No
article_type: original
author:
- first_name: Pradeep
  full_name: Bhandari, Pradeep
  id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87
  last_name: Bhandari
  orcid: 0000-0003-0863-4481
- first_name: David H
  full_name: Vandael, David H
  id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87
  last_name: Vandael
  orcid: 0000-0001-7577-1676
- first_name: Diego
  full_name: Fernández-Fernández, Diego
  last_name: Fernández-Fernández
- first_name: Thorsten
  full_name: Fritzius, Thorsten
  last_name: Fritzius
- first_name: David
  full_name: Kleindienst, David
  id: 42E121A4-F248-11E8-B48F-1D18A9856A87
  last_name: Kleindienst
- first_name: Hüseyin C
  full_name: Önal, Hüseyin C
  id: 4659D740-F248-11E8-B48F-1D18A9856A87
  last_name: Önal
  orcid: 0000-0002-2771-2011
- first_name: Jacqueline-Claire
  full_name: Montanaro-Punzengruber, Jacqueline-Claire
  id: 3786AB44-F248-11E8-B48F-1D18A9856A87
  last_name: Montanaro-Punzengruber
- first_name: Martin
  full_name: Gassmann, Martin
  last_name: Gassmann
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
- first_name: Akos
  full_name: Kulik, Akos
  last_name: Kulik
- first_name: Bernhard
  full_name: Bettler, Bernhard
  last_name: Bettler
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
  orcid: 0000-0002-3509-1948
citation:
  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>
  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>
  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.
  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>.
  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).
date_created: 2021-05-30T22:01:23Z
date_published: 2021-04-29T00:00:00Z
date_updated: 2026-09-13T22:31:04Z
day: '29'
ddc:
- '570'
department:
- _id: RySh
- _id: PeJo
doi: 10.7554/ELIFE.68274
ec_funded: 1
external_id:
  isi:
  - '000651761700001'
  pmid:
  - '33913808'
file:
- access_level: open_access
  checksum: 6ebcb79999f889766f7cd79ee134ad28
  content_type: application/pdf
  creator: cziletti
  date_created: 2021-05-31T09:43:09Z
  date_updated: 2021-05-31T09:43:09Z
  file_id: '9440'
  file_name: 2021_eLife_Bhandari.pdf
  file_size: 8174719
  relation: main_file
  success: 1
file_date_updated: 2021-05-31T09:43:09Z
fulldoi: https://doi.org/10.7554/ELIFE.68274
has_accepted_license: '1'
intvolume: '        10'
isi: 1
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25CA28EA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '694539'
  name: 'In situ analysis of single channel subunit composition in neurons: physiological
    implication in synaptic plasticity and behaviour'
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
  link:
  - relation: earlier_version
    url: https://doi.org/10.1101/2020.04.16.045112
  record:
  - id: '19271'
    relation: dissertation_contains
    status: public
  - id: '9562'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial
  habenula terminals
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 10
year: '2021'
...
---
_id: '7398'
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.'
article_processing_charge: No
article_type: original
author:
- first_name: Fatma Asli
  full_name: Erdem, Fatma Asli
  last_name: Erdem
- first_name: Marija
  full_name: Ilic, Marija
  last_name: Ilic
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
  orcid: 0000-0002-3509-1948
- 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
- first_name: Walter
  full_name: Sandtner, Walter
  last_name: Sandtner
citation:
  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>
  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>
  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>.
  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.
  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.
  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>.
  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.
date_created: 2020-01-29T16:06:29Z
date_published: 2019-07-03T00:00:00Z
date_updated: 2023-09-07T14:52:23Z
day: '03'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1085/jgp.201912318
external_id:
  isi:
  - '000478792500008'
  pmid:
  - '31270129'
file:
- access_level: open_access
  checksum: 5706b4ccd74ee3e50bf7ecb2a203df71
  content_type: application/pdf
  creator: dernst
  date_created: 2020-02-05T07:20:32Z
  date_updated: 2020-07-14T12:47:57Z
  file_id: '7450'
  file_name: 2019_JGP_Erdem.pdf
  file_size: 2641297
  relation: main_file
file_date_updated: 2020-07-14T12:47:57Z
fulldoi: https://doi.org/10.1085/jgp.201912318
has_accepted_license: '1'
intvolume: '       151'
isi: 1
issue: '8'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 1035-1050
pmid: 1
publication: The Journal of General Physiology
publication_identifier:
  eissn:
  - 1540-7748
  issn:
  - 0022-1295
publication_status: published
publisher: Rockefeller University Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: A comparison of the transport kinetics of glycine transporter 1 and glycine
  transporter 2
tmp:
  image: /images/cc_by_nc_sa.png
  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)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 151
year: '2019'
...
