---
_id: '14794'
abstract:
- lang: eng
  text: "Mosaic analysis with double markers (MADM) technology enables the sparse
    labeling of genetically defined neurons. We present a protocol for time-lapse
    imaging of cortical projection neuron migration in mice using MADM. We describe
    steps for the isolation, culturing, and 4D imaging of neuronal dynamics in MADM-labeled
    brain tissue. While this protocol is compatible with other single-cell labeling
    methods, the MADM approach provides a genetic platform for the functional assessment
    of cell-autonomous candidate gene function and the relative contribution of non-cell-autonomous
    effects.\r\n\r\nFor complete details on the use and execution of this protocol,
    please refer to Hansen et al. (2022),1 Contreras et al. (2021),2 and Amberg and
    Hippenmeyer (2021).3"
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: We thank Florian Pauler for discussion and his expert technical support.
  This research was supported by the Scientific Service Units (SSU) at IST Austria
  through resources provided by the Imaging and Optics Facility (IOF) and Preclinical
  Facility (PCF). A.H.H. was a recipient of a DOC Fellowship (24812) of the Austrian
  Academy of Sciences.
article_number: '102795'
article_processing_charge: Yes
article_type: review
author:
- first_name: Andi H
  full_name: Hansen, Andi H
  id: 38853E16-F248-11E8-B48F-1D18A9856A87
  last_name: Hansen
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
citation:
  ama: Hansen AH, Hippenmeyer S. Time-lapse imaging of cortical projection neuron
    migration in mice using mosaic analysis with double markers. <i>STAR Protocols</i>.
    2024;5(1). doi:<a href="https://doi.org/10.1016/j.xpro.2023.102795">10.1016/j.xpro.2023.102795</a>
  apa: Hansen, A. H., &#38; Hippenmeyer, S. (2024). Time-lapse imaging of cortical
    projection neuron migration in mice using mosaic analysis with double markers.
    <i>STAR Protocols</i>. Elsevier. <a href="https://doi.org/10.1016/j.xpro.2023.102795">https://doi.org/10.1016/j.xpro.2023.102795</a>
  chicago: Hansen, Andi H, and Simon Hippenmeyer. “Time-Lapse Imaging of Cortical
    Projection Neuron Migration in Mice Using Mosaic Analysis with Double Markers.”
    <i>STAR Protocols</i>. Elsevier, 2024. <a href="https://doi.org/10.1016/j.xpro.2023.102795">https://doi.org/10.1016/j.xpro.2023.102795</a>.
  ieee: A. H. Hansen and S. Hippenmeyer, “Time-lapse imaging of cortical projection
    neuron migration in mice using mosaic analysis with double markers,” <i>STAR Protocols</i>,
    vol. 5, no. 1. Elsevier, 2024.
  ista: Hansen AH, Hippenmeyer S. 2024. Time-lapse imaging of cortical projection
    neuron migration in mice using mosaic analysis with double markers. STAR Protocols.
    5(1), 102795.
  mla: Hansen, Andi H., and Simon Hippenmeyer. “Time-Lapse Imaging of Cortical Projection
    Neuron Migration in Mice Using Mosaic Analysis with Double Markers.” <i>STAR Protocols</i>,
    vol. 5, no. 1, 102795, Elsevier, 2024, doi:<a href="https://doi.org/10.1016/j.xpro.2023.102795">10.1016/j.xpro.2023.102795</a>.
  short: A.H. Hansen, S. Hippenmeyer, STAR Protocols 5 (2024).
date_created: 2024-01-14T23:00:56Z
date_published: 2024-01-01T00:00:00Z
date_updated: 2025-08-11T11:49:30Z
day: '01'
department:
- _id: SiHi
doi: 10.1016/j.xpro.2023.102795
external_id:
  oaworkID:
  - '34426698 '
  pmid:
  - '38165800'
intvolume: '         5'
issue: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1016/j.xpro.2023.102795
month: '01'
oa: 1
oa_version: Published Version
oaworkID: 1
pmid: 1
project:
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
  grant_number: '24812'
  name: Molecular Mechanisms of Radial Neuronal Migration
publication: STAR Protocols
publication_identifier:
  eissn:
  - 2666-1667
publication_status: epub_ahead
publisher: Elsevier
quality_controlled: '1'
related_material:
  link:
  - relation: software
    url: http://github.com/hippenmeyerlab
scopus_import: '1'
status: public
title: Time-lapse imaging of cortical projection neuron migration in mice using mosaic
  analysis with double markers
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 5
year: '2024'
...
---
_id: '14795'
abstract:
- lang: eng
  text: Metazoan development relies on the formation and remodeling of cell-cell contacts.
    Dynamic reorganization of adhesion receptors and the actomyosin cell cortex in
    space and time plays a central role in cell-cell contact formation and maturation.
    Nevertheless, how this process is mechanistically achieved when new contacts are
    formed remains unclear. Here, by building a biomimetic assay composed of progenitor
    cells adhering to supported lipid bilayers functionalized with E-cadherin ectodomains,
    we show that cortical F-actin flows, driven by the depletion of myosin-2 at the
    cell contact center, mediate the dynamic reorganization of adhesion receptors
    and cell cortex at the contact. E-cadherin-dependent downregulation of the small
    GTPase RhoA at the forming contact leads to both a depletion of myosin-2 and a
    decrease of F-actin at the contact center. At the contact rim, in contrast, myosin-2
    becomes enriched by the retraction of bleb-like protrusions, resulting in a cortical
    tension gradient from the contact rim to its center. This tension gradient, in
    turn, triggers centrifugal F-actin flows, leading to further accumulation of F-actin
    at the contact rim and the progressive redistribution of E-cadherin from the contact
    center to the rim. Eventually, this combination of actomyosin downregulation and
    flows at the contact determines the characteristic molecular organization, with
    E-cadherin and F-actin accumulating at the contact rim, where they are needed
    to mechanically link the contractile cortices of the adhering cells.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: "We are grateful to Edwin Munro for their feedback and help with
  the single particle analysis. We thank members of the Heisenberg and Loose labs
  for their help and feedback on the manuscript, notably Xin Tong for making the PCS2-mCherry-AHPH
  plasmid. Finally, we thank the Aquatics and Imaging & Optics facilities of ISTA
  for their continuous support, especially Yann Cesbron for assistance with the laser
  cutter. This work was supported by an ERC\r\nAdvanced Grant (MECSPEC) to C.-P.H."
article_processing_charge: Yes (via OA deal)
article_type: original
arxiv: 1
author:
- first_name: Feyza N
  full_name: Arslan, Feyza N
  id: 49DA7910-F248-11E8-B48F-1D18A9856A87
  last_name: Arslan
  orcid: 0000-0001-5809-9566
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Jack
  full_name: Merrin, Jack
  id: 4515C308-F248-11E8-B48F-1D18A9856A87
  last_name: Merrin
  orcid: 0000-0001-5145-4609
- first_name: Martin
  full_name: Loose, Martin
  id: 462D4284-F248-11E8-B48F-1D18A9856A87
  last_name: Loose
  orcid: 0000-0001-7309-9724
- first_name: Carl-Philipp J
  full_name: Heisenberg, Carl-Philipp J
  id: 39427864-F248-11E8-B48F-1D18A9856A87
  last_name: Heisenberg
  orcid: 0000-0002-0912-4566
citation:
  ama: Arslan FN, Hannezo EB, Merrin J, Loose M, Heisenberg C-PJ. Adhesion-induced
    cortical flows pattern E-cadherin-mediated cell contacts. <i>Current Biology</i>.
    2024;34(1):171-182.e8. doi:<a href="https://doi.org/10.1016/j.cub.2023.11.067">10.1016/j.cub.2023.11.067</a>
  apa: Arslan, F. N., Hannezo, E. B., Merrin, J., Loose, M., &#38; Heisenberg, C.-P.
    J. (2024). Adhesion-induced cortical flows pattern E-cadherin-mediated cell contacts.
    <i>Current Biology</i>. Elsevier. <a href="https://doi.org/10.1016/j.cub.2023.11.067">https://doi.org/10.1016/j.cub.2023.11.067</a>
  chicago: Arslan, Feyza N, Edouard B Hannezo, Jack Merrin, Martin Loose, and Carl-Philipp
    J Heisenberg. “Adhesion-Induced Cortical Flows Pattern E-Cadherin-Mediated Cell
    Contacts.” <i>Current Biology</i>. Elsevier, 2024. <a href="https://doi.org/10.1016/j.cub.2023.11.067">https://doi.org/10.1016/j.cub.2023.11.067</a>.
  ieee: F. N. Arslan, E. B. Hannezo, J. Merrin, M. Loose, and C.-P. J. Heisenberg,
    “Adhesion-induced cortical flows pattern E-cadherin-mediated cell contacts,” <i>Current
    Biology</i>, vol. 34, no. 1. Elsevier, p. 171–182.e8, 2024.
  ista: Arslan FN, Hannezo EB, Merrin J, Loose M, Heisenberg C-PJ. 2024. Adhesion-induced
    cortical flows pattern E-cadherin-mediated cell contacts. Current Biology. 34(1),
    171–182.e8.
  mla: Arslan, Feyza N., et al. “Adhesion-Induced Cortical Flows Pattern E-Cadherin-Mediated
    Cell Contacts.” <i>Current Biology</i>, vol. 34, no. 1, Elsevier, 2024, p. 171–182.e8,
    doi:<a href="https://doi.org/10.1016/j.cub.2023.11.067">10.1016/j.cub.2023.11.067</a>.
  short: F.N. Arslan, E.B. Hannezo, J. Merrin, M. Loose, C.-P.J. Heisenberg, Current
    Biology 34 (2024) 171–182.e8.
corr_author: '1'
date_created: 2024-01-14T23:00:56Z
date_published: 2024-01-08T00:00:00Z
date_updated: 2025-07-22T14:58:27Z
day: '08'
ddc:
- '570'
department:
- _id: CaHe
- _id: EdHa
- _id: MaLo
- _id: NanoFab
doi: 10.1016/j.cub.2023.11.067
ec_funded: 1
external_id:
  arxiv:
  - '2410.03589'
file:
- access_level: open_access
  checksum: 51220b76d72a614208f84bdbfbaf9b72
  content_type: application/pdf
  creator: dernst
  date_created: 2024-01-16T10:53:31Z
  date_updated: 2024-01-16T10:53:31Z
  file_id: '14813'
  file_name: 2024_CurrentBiology_Arslan.pdf
  file_size: 5183861
  relation: main_file
  success: 1
file_date_updated: 2024-01-16T10:53:31Z
has_accepted_license: '1'
intvolume: '        34'
issue: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: 171-182.e8
project:
- _id: 260F1432-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '742573'
  name: Interaction and feedback between cell mechanics and fate specification in
    vertebrate gastrulation
publication: Current Biology
publication_identifier:
  eissn:
  - 1879-0445
  issn:
  - 0960-9822
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Adhesion-induced cortical flows pattern E-cadherin-mediated cell contacts
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: 34
year: '2024'
...
---
_id: '14843'
abstract:
- lang: eng
  text: The coupling between Ca2+ channels and release sensors is a key factor defining
    the signaling properties of a synapse. However, the coupling nanotopography at
    many synapses remains unknown, and it is unclear how it changes during development.
    To address these questions, we examined coupling at the cerebellar inhibitory
    basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission
    by paired recording and intracellular pipette perfusion revealed that the effects
    of exogenous Ca2+ chelators decreased during development, despite constant reliance
    of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica
    labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic
    P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked
    vesicles were only clustered at later developmental stages. Modeling suggested
    a developmental transformation from a more random to a more clustered coupling
    nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point
    configuration, optimizing speed, reliability, and energy efficiency of synaptic
    transmission.
acknowledged_ssus:
- _id: EM-Fac
- _id: PreCl
- _id: M-Shop
acknowledgement: We thank Drs. David DiGregorio and Erwin Neher for critically reading
  an earlier version of the manuscript, Ralf Schneggenburger for helpful discussions,
  Benjamin Suter and Katharina Lichter for support with image analysis, Chris Wojtan
  for advice on numerical solution of partial differential equations, Maria Reva for
  help with Ripley analysis, Alois Schlögl for programming, and Akari Hagiwara and
  Toshihisa Ohtsuka for anti-ELKS antibody. We are grateful to Florian Marr, Christina
  Altmutter, and Vanessa Zheden for excellent technical assistance and to Eleftheria
  Kralli-Beller for manuscript editing. This research was supported by the Scientific
  Services Units (SSUs) of ISTA (Electron Microscopy Facility, Preclinical Facility,
  and Machine Shop). The project received funding from the European Research Council
  (ERC) under the European Union’s Horizon 2020 research and innovation program (grant
  agreement no. 692692), the Fonds zur Förderung der Wissenschaftlichen Forschung
  (Z 312-B27, Wittgenstein award; P 36232-B), all to P.J., and a DOC fellowship of
  the Austrian Academy of Sciences to J.-J.C.
article_processing_charge: No
article_type: original
author:
- first_name: JingJing
  full_name: Chen, JingJing
  id: 2C4E65C8-F248-11E8-B48F-1D18A9856A87
  last_name: Chen
- first_name: Walter
  full_name: Kaufmann, Walter
  id: 3F99E422-F248-11E8-B48F-1D18A9856A87
  last_name: Kaufmann
  orcid: 0000-0001-9735-5315
- first_name: Chong
  full_name: Chen, Chong
  id: 3DFD581A-F248-11E8-B48F-1D18A9856A87
  last_name: Chen
- first_name: Itaru
  full_name: Arai, Itaru
  id: 32A73F6C-F248-11E8-B48F-1D18A9856A87
  last_name: Arai
- first_name: Olena
  full_name: Kim, Olena
  id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87
  last_name: Kim
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
citation:
  ama: Chen J, Kaufmann W, Chen C, et al. Developmental transformation of Ca2+ channel-vesicle
    nanotopography at a central GABAergic synapse. <i>Neuron</i>. doi:<a href="https://doi.org/10.1016/j.neuron.2023.12.002">10.1016/j.neuron.2023.12.002</a>
  apa: Chen, J., Kaufmann, W., Chen, C., Arai,  itaru, Kim, O., Shigemoto, R., &#38;
    Jonas, P. M. (n.d.). Developmental transformation of Ca2+ channel-vesicle nanotopography
    at a central GABAergic synapse. <i>Neuron</i>. Elsevier. <a href="https://doi.org/10.1016/j.neuron.2023.12.002">https://doi.org/10.1016/j.neuron.2023.12.002</a>
  chicago: Chen, JingJing, Walter Kaufmann, Chong Chen, itaru Arai, Olena Kim, Ryuichi
    Shigemoto, and Peter M Jonas. “Developmental Transformation of Ca2+ Channel-Vesicle
    Nanotopography at a Central GABAergic Synapse.” <i>Neuron</i>. Elsevier, n.d.
    <a href="https://doi.org/10.1016/j.neuron.2023.12.002">https://doi.org/10.1016/j.neuron.2023.12.002</a>.
  ieee: J. Chen <i>et al.</i>, “Developmental transformation of Ca2+ channel-vesicle
    nanotopography at a central GABAergic synapse,” <i>Neuron</i>. Elsevier.
  ista: Chen J, Kaufmann W, Chen C, Arai  itaru, Kim O, Shigemoto R, Jonas PM. Developmental
    transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse.
    Neuron.
  mla: Chen, JingJing, et al. “Developmental Transformation of Ca2+ Channel-Vesicle
    Nanotopography at a Central GABAergic Synapse.” <i>Neuron</i>, Elsevier, doi:<a
    href="https://doi.org/10.1016/j.neuron.2023.12.002">10.1016/j.neuron.2023.12.002</a>.
  short: J. Chen, W. Kaufmann, C. Chen,  itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas,
    Neuron (n.d.).
date_created: 2024-01-21T23:00:56Z
date_published: 2024-01-11T00:00:00Z
date_updated: 2024-03-05T09:31:24Z
day: '11'
department:
- _id: PeJo
- _id: EM-Fac
- _id: RySh
doi: 10.1016/j.neuron.2023.12.002
ec_funded: 1
external_id:
  pmid:
  - '38215739'
language:
- iso: eng
month: '01'
oa_version: None
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z00312
  name: The Wittgenstein Prize
- _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5
  grant_number: P36232
  name: Mechanisms of GABA release in hippocampal circuits
- _id: 26B66A3E-B435-11E9-9278-68D0E5697425
  grant_number: '25383'
  name: Development of nanodomain coupling between Ca2+ channels and release sensors
    at a central inhibitory synapse
publication: Neuron
publication_identifier:
  eissn:
  - 1097-4199
  issn:
  - 0896-6273
publication_status: inpress
publisher: Elsevier
quality_controlled: '1'
related_material:
  link:
  - description: News on ISTA Website
    relation: press_release
    url: https://ista.ac.at/en/news/synapses-brought-to-the-point/
scopus_import: '1'
status: public
title: Developmental transformation of Ca2+ channel-vesicle nanotopography at a central
  GABAergic synapse
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2024'
...
---
_id: '12875'
abstract:
- lang: eng
  text: The superior colliculus (SC) in the mammalian midbrain is essential for multisensory
    integration and is composed of a rich diversity of excitatory and inhibitory neurons
    and glia. However, the developmental principles directing the generation of SC
    cell-type diversity are not understood. Here, we pursued systematic cell lineage
    tracing in silico and in vivo, preserving full spatial information, using genetic
    mosaic analysis with double markers (MADM)-based clonal analysis with single-cell
    sequencing (MADM-CloneSeq). The analysis of clonally related cell lineages revealed
    that radial glial progenitors (RGPs) in SC are exceptionally multipotent. Individual
    resident RGPs have the capacity to produce all excitatory and inhibitory SC neuron
    types, even at the stage of terminal division. While individual clonal units show
    no pre-defined cellular composition, the establishment of appropriate relative
    proportions of distinct neuronal types occurs in a PTEN-dependent manner. Collectively,
    our findings provide an inaugural framework at the single-RGP/-cell level of the
    mammalian SC ontogeny.
acknowledged_ssus:
- _id: Bio
- _id: M-Shop
- _id: LifeSc
- _id: PreCl
acknowledgement: "We thank Liqun Luo for his continued support, for providing essential
  resources for generating Fzd10-CreER mice which were generated in his laboratory,
  and for comments on the manuscript; W. Zhong for providing Nestin-Cre transgenic
  mouse line for this study; A. Heger for mouse colony management; R. Beattie and
  T. Asenov for designing and producing components of acute slice recovery chamber
  for MADM-CloneSeq experiments; and K. Leopold, J. Rodarte and N. Amberg for initial
  experiments, technical support and/or assistance. This study was supported by the
  Scientific Service Units (SSU) of IST Austria through resources provided by the
  Imaging & Optics Facility (IOF), Laboratory Support Facility (LSF), Miba Machine
  Shop, and Pre-clinical Facility (PCF). G.C. received funding from European Commission
  (IST plus postdoctoral fellowship). This work was supported by ISTA institutional\r\nfunds;
  the Austrian Science Fund Special Research Programmes (FWF SFB F78 Neuro Stem Modulation)
  to S.H. "
article_processing_charge: Yes (via OA deal)
article_type: comment
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
date_created: 2023-04-27T09:41:48Z
date_published: 2024-01-17T00:00:00Z
date_updated: 2025-05-14T09:39:37Z
day: '17'
ddc:
- '570'
department:
- _id: SiHi
- _id: RySh
doi: 10.1016/j.neuron.2023.11.009
external_id:
  pmid:
  - '38096816'
file:
- access_level: open_access
  checksum: 32b3788f7085cf44a84108d8faaff3ce
  content_type: application/pdf
  creator: dernst
  date_created: 2024-02-06T13:56:15Z
  date_updated: 2024-02-06T13:56:15Z
  file_id: '14944'
  file_name: 2024_Neuron_Cheung.pdf
  file_size: 5942467
  relation: main_file
  success: 1
file_date_updated: 2024-02-06T13:56:15Z
has_accepted_license: '1'
intvolume: '       112'
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: F07805
  name: Molecular Mechanisms of Neural Stem Cell Lineage Progression
publication: Neuron
publication_identifier:
  eisbn:
  - '1234995621'
  issn:
  - 0896-6273
  issnl:
  - 1234-5678
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: '14323'
abstract:
- lang: eng
  text: Morphogens are signaling molecules that are known for their prominent role
    in pattern formation within developing tissues. In addition to patterning, morphogens
    also control tissue growth. However, the underlying mechanisms are poorly understood.
    We studied the role of morphogens in regulating tissue growth in the developing
    vertebrate neural tube. In this system, opposing morphogen gradients of Shh and
    BMP establish the dorsoventral pattern of neural progenitor domains. Perturbations
    in these morphogen pathways result in alterations in tissue growth and cell cycle
    progression, however, it has been unclear what cellular process is affected. To
    address this, we analysed the rates of cell proliferation and cell death in mouse
    mutants in which signaling is perturbed, as well as in chick neural plate explants
    exposed to defined concentrations of signaling activators or inhibitors. Our results
    indicated that the rate of cell proliferation was not altered in these assays.
    By contrast, both the Shh and BMP signaling pathways had profound effects on neural
    progenitor survival. Our results indicate that these pathways synergise to promote
    cell survival within neural progenitors. Consistent with this, we found that progenitors
    within the intermediate region of the neural tube, where the combined levels of
    Shh and BMP are the lowest, are most prone to cell death when signaling activity
    is inhibited. In addition, we found that downregulation of Shh results in increased
    apoptosis within the roof plate, which is the dorsal source of BMP ligand production.
    This revealed a cross-interaction between the Shh and BMP morphogen signaling
    pathways that may be relevant for understanding how gradients scale in neural
    tubes with different overall sizes. We further studied the mechanism acting downstream
    of Shh in cell survival regulation using genetic and genomic approaches. We propose
    that Shh transcriptionally regulates a non-canonical apoptotic pathway. Altogether,
    our study points to a novel role of opposing morphogen gradients in tissue size
    regulation and provides new insights into complex interactions between Shh and
    BMP signaling gradients in the neural tube.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Katarzyna
  full_name: Kuzmicz-Kowalska, Katarzyna
  id: 4CED352A-F248-11E8-B48F-1D18A9856A87
  last_name: Kuzmicz-Kowalska
citation:
  ama: Kuzmicz-Kowalska K. Regulation of neural progenitor survival by Shh and BMP
    in the developing spinal cord. 2023. doi:<a href="https://doi.org/10.15479/at:ista:14323">10.15479/at:ista:14323</a>
  apa: Kuzmicz-Kowalska, K. (2023). <i>Regulation of neural progenitor survival by
    Shh and BMP in the developing spinal cord</i>. Institute of Science and Technology
    Austria. <a href="https://doi.org/10.15479/at:ista:14323">https://doi.org/10.15479/at:ista:14323</a>
  chicago: Kuzmicz-Kowalska, Katarzyna. “Regulation of Neural Progenitor Survival
    by Shh and BMP in the Developing Spinal Cord.” Institute of Science and Technology
    Austria, 2023. <a href="https://doi.org/10.15479/at:ista:14323">https://doi.org/10.15479/at:ista:14323</a>.
  ieee: K. Kuzmicz-Kowalska, “Regulation of neural progenitor survival by Shh and
    BMP in the developing spinal cord,” Institute of Science and Technology Austria,
    2023.
  ista: Kuzmicz-Kowalska K. 2023. Regulation of neural progenitor survival by Shh
    and BMP in the developing spinal cord. Institute of Science and Technology Austria.
  mla: Kuzmicz-Kowalska, Katarzyna. <i>Regulation of Neural Progenitor Survival by
    Shh and BMP in the Developing Spinal Cord</i>. Institute of Science and Technology
    Austria, 2023, doi:<a href="https://doi.org/10.15479/at:ista:14323">10.15479/at:ista:14323</a>.
  short: K. Kuzmicz-Kowalska, Regulation of Neural Progenitor Survival by Shh and
    BMP in the Developing Spinal Cord, Institute of Science and Technology Austria,
    2023.
date_created: 2023-09-13T10:07:18Z
date_published: 2023-09-13T00:00:00Z
date_updated: 2024-03-07T15:02:59Z
day: '13'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: AnKi
doi: 10.15479/at:ista:14323
file:
- access_level: closed
  checksum: bd83596869c814b24aeff7077d031c0e
  content_type: application/pdf
  creator: kkuzmicz
  date_created: 2023-09-13T09:52:52Z
  date_updated: 2023-09-13T10:08:25Z
  embargo: 2025-03-13
  embargo_to: open_access
  file_id: '14324'
  file_name: PhDThesis_KK_final_pdfA.pdf
  file_size: 10147911
  relation: main_file
- access_level: closed
  checksum: aa2757ae4c3478041fd7e62c587d3e4d
  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
  creator: kkuzmicz
  date_created: 2023-09-13T09:53:29Z
  date_updated: 2023-09-13T09:53:29Z
  file_id: '14325'
  file_name: thesis_KK_final_corrections_092023.docx
  file_size: 103980668
  relation: source_file
file_date_updated: 2023-09-13T10:08:25Z
has_accepted_license: '1'
language:
- iso: eng
month: '09'
oa_version: Published Version
page: '151'
project:
- _id: 267AF0E4-B435-11E9-9278-68D0E5697425
  name: The role of morphogens in the regulation of neural tube growth
publication_identifier:
  issn:
  - 2663 - 337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '7883'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Anna
  full_name: Kicheva, Anna
  id: 3959A2A0-F248-11E8-B48F-1D18A9856A87
  last_name: Kicheva
  orcid: 0000-0003-4509-4998
title: Regulation of neural progenitor survival by Shh and BMP in the developing spinal
  cord
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: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2023'
...
---
_id: '14363'
abstract:
- lang: eng
  text: Mitochondrial networks remodel their connectivity, content, and subcellular
    localization to support optimized energy production in conditions of increased
    environmental or cellular stress. Microglia rely on mitochondria to respond to
    these stressors, however our knowledge about mitochondrial networks and their
    adaptations in microglia in vivo is limited. Here, we generate a mouse model that
    selectively labels mitochondria in microglia. We identify that mitochondrial networks
    are more fragmented with increased content and perinuclear localization in vitro
    vs. in vivo. Mitochondrial networks adapt similarly in microglia closest to the
    injury site after optic nerve crush. Preventing microglial UCP2 increase after
    injury by selective knockout induces cellular stress. This results in mitochondrial
    hyperfusion in male microglia, a phenotype absent in females due to circulating
    estrogens. Our results establish the foundation for mitochondrial network analysis
    of microglia in vivo, emphasizing the importance of mitochondrial-based sex effects
    of microglia in other pathologies.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: We thank the Scientific Service Units (SSU) of ISTA through resources
  provided by the Imaging and Optics Facility (IOF), the Lab Support Facility (LSF),
  and the Pre-Clinical Facility (PCF) team, specifically Sonja Haslinger and Michael
  Schunn for excellent mouse colony management and support. This research was supported
  by the FWF Sonderforschungsbereich F83 (to E.E.P). We thank Bálint Nagy, Ryan John
  A. Cubero, Marco Benevento and all members of the Siegert group for constant feedback
  on the project and article.
article_number: '107780'
article_processing_charge: Yes
article_type: original
author:
- first_name: Margaret E
  full_name: Maes, Margaret E
  id: 3838F452-F248-11E8-B48F-1D18A9856A87
  last_name: Maes
  orcid: 0000-0001-9642-1085
- first_name: Gloria
  full_name: Colombo, Gloria
  id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
  last_name: Colombo
  orcid: 0000-0001-9434-8902
- first_name: Florianne E
  full_name: Schoot Uiterkamp, Florianne E
  id: 3526230C-F248-11E8-B48F-1D18A9856A87
  last_name: Schoot Uiterkamp
- first_name: Felix
  full_name: Sternberg, Felix
  last_name: Sternberg
- first_name: Alessandro
  full_name: Venturino, Alessandro
  id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
  last_name: Venturino
  orcid: 0000-0003-2356-9403
- first_name: Elena E.
  full_name: Pohl, Elena E.
  last_name: Pohl
- first_name: Sandra
  full_name: Siegert, Sandra
  id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
  last_name: Siegert
  orcid: 0000-0001-8635-0877
citation:
  ama: Maes ME, Colombo G, Schoot Uiterkamp FE, et al. Mitochondrial network adaptations
    of microglia reveal sex-specific stress response after injury and UCP2 knockout.
    <i>iScience</i>. 2023;26(10). doi:<a href="https://doi.org/10.1016/j.isci.2023.107780">10.1016/j.isci.2023.107780</a>
  apa: Maes, M. E., Colombo, G., Schoot Uiterkamp, F. E., Sternberg, F., Venturino,
    A., Pohl, E. E., &#38; Siegert, S. (2023). Mitochondrial network adaptations of
    microglia reveal sex-specific stress response after injury and UCP2 knockout.
    <i>IScience</i>. Elsevier. <a href="https://doi.org/10.1016/j.isci.2023.107780">https://doi.org/10.1016/j.isci.2023.107780</a>
  chicago: Maes, Margaret E, Gloria Colombo, Florianne E Schoot Uiterkamp, Felix Sternberg,
    Alessandro Venturino, Elena E. Pohl, and Sandra Siegert. “Mitochondrial Network
    Adaptations of Microglia Reveal Sex-Specific Stress Response after Injury and
    UCP2 Knockout.” <i>IScience</i>. Elsevier, 2023. <a href="https://doi.org/10.1016/j.isci.2023.107780">https://doi.org/10.1016/j.isci.2023.107780</a>.
  ieee: M. E. Maes <i>et al.</i>, “Mitochondrial network adaptations of microglia
    reveal sex-specific stress response after injury and UCP2 knockout,” <i>iScience</i>,
    vol. 26, no. 10. Elsevier, 2023.
  ista: Maes ME, Colombo G, Schoot Uiterkamp FE, Sternberg F, Venturino A, Pohl EE,
    Siegert S. 2023. Mitochondrial network adaptations of microglia reveal sex-specific
    stress response after injury and UCP2 knockout. iScience. 26(10), 107780.
  mla: Maes, Margaret E., et al. “Mitochondrial Network Adaptations of Microglia Reveal
    Sex-Specific Stress Response after Injury and UCP2 Knockout.” <i>IScience</i>,
    vol. 26, no. 10, 107780, Elsevier, 2023, doi:<a href="https://doi.org/10.1016/j.isci.2023.107780">10.1016/j.isci.2023.107780</a>.
  short: M.E. Maes, G. Colombo, F.E. Schoot Uiterkamp, F. Sternberg, A. Venturino,
    E.E. Pohl, S. Siegert, IScience 26 (2023).
date_created: 2023-09-24T22:01:11Z
date_published: 2023-10-20T00:00:00Z
date_updated: 2023-12-13T12:27:30Z
day: '20'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1016/j.isci.2023.107780
external_id:
  isi:
  - '001080403500001'
  pmid:
  - '37731609'
file:
- access_level: open_access
  checksum: be1a560efdd96d20712311f4fc54aac2
  content_type: application/pdf
  creator: dernst
  date_created: 2023-11-07T08:53:21Z
  date_updated: 2023-11-07T08:53:21Z
  file_id: '14497'
  file_name: 2023_iScience_Maes.pdf
  file_size: 8197935
  relation: main_file
  success: 1
file_date_updated: 2023-11-07T08:53:21Z
has_accepted_license: '1'
intvolume: '        26'
isi: 1
issue: '10'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
pmid: 1
publication: iScience
publication_identifier:
  eissn:
  - 2589-0042
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Mitochondrial network adaptations of microglia reveal sex-specific stress response
  after injury and UCP2 knockout
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: 26
year: '2023'
...
---
_id: '14644'
abstract:
- lang: eng
  text: Transcription by RNA polymerase II (Pol II) can be repressed by noncoding
    RNA, including the human RNA Alu. However, the mechanism by which endogenous RNAs
    repress transcription remains unclear. Here we present cryo-electron microscopy
    structures of Pol II bound to Alu RNA, which reveal that Alu RNA mimics how DNA
    and RNA bind to Pol II during transcription elongation. Further, we show how domains
    of the general transcription factor TFIIF affect complex dynamics and control
    repressive activity. Together, we reveal how a non-coding RNA can regulate mammalian
    gene expression.
acknowledged_ssus:
- _id: LifeSc
- _id: EM-Fac
- _id: PreCl
acknowledgement: "We thank B. Kaczmarek and other members of the Bernecky lab for
  helpful discussions. We thank V.-V. Hodirnau for SerialEM data collection and support
  with EPU data collection. We thank D. Slade for the wild type TFIIF expression\r\nplasmid.
  We thank N. Thompson and R. Burgess for the 8WG16 hybridoma cell line. We thank
  C. Plaschka and M. Loose for critical reading of the manuscript. This work was supported
  by Austrian Science Fund (FWF) grant P34185. This research was further supported
  by the Scientific Service Units (SSU) of IST Austria through resources provided
  by the Lab Support Facility (LSF), Electron Microscopy Facility (EMF), Scientific
  Computing (SciComp), and the Preclinical Facility (PCF)."
article_processing_charge: No
author:
- first_name: Katarina
  full_name: Tluckova, Katarina
  id: 4AC7D980-F248-11E8-B48F-1D18A9856A87
  last_name: Tluckova
- first_name: Anita P
  full_name: Testa Salmazo, Anita P
  id: 41F1F098-F248-11E8-B48F-1D18A9856A87
  last_name: Testa Salmazo
- first_name: Carrie A
  full_name: Bernecky, Carrie A
  id: 2CB9DFE2-F248-11E8-B48F-1D18A9856A87
  last_name: Bernecky
  orcid: 0000-0003-0893-7036
citation:
  ama: Tluckova K, Testa Salmazo AP, Bernecky C. Mechanism of mammalian transcriptional
    repression by noncoding RNA. doi:<a href="https://doi.org/10.15479/AT:ISTA:14644">10.15479/AT:ISTA:14644</a>
  apa: Tluckova, K., Testa Salmazo, A. P., &#38; Bernecky, C. (n.d.). Mechanism of
    mammalian transcriptional repression by noncoding RNA. Institute of Science and
    Technology Austria. <a href="https://doi.org/10.15479/AT:ISTA:14644">https://doi.org/10.15479/AT:ISTA:14644</a>
  chicago: Tluckova, Katarina, Anita P Testa Salmazo, and Carrie Bernecky. “Mechanism
    of Mammalian Transcriptional Repression by Noncoding RNA.” Institute of Science
    and Technology Austria, n.d. <a href="https://doi.org/10.15479/AT:ISTA:14644">https://doi.org/10.15479/AT:ISTA:14644</a>.
  ieee: K. Tluckova, A. P. Testa Salmazo, and C. Bernecky, “Mechanism of mammalian
    transcriptional repression by noncoding RNA.” Institute of Science and Technology
    Austria.
  ista: Tluckova K, Testa Salmazo AP, Bernecky C. Mechanism of mammalian transcriptional
    repression by noncoding RNA. <a href="https://doi.org/10.15479/AT:ISTA:14644">10.15479/AT:ISTA:14644</a>.
  mla: Tluckova, Katarina, et al. <i>Mechanism of Mammalian Transcriptional Repression
    by Noncoding RNA</i>. Institute of Science and Technology Austria, doi:<a href="https://doi.org/10.15479/AT:ISTA:14644">10.15479/AT:ISTA:14644</a>.
  short: K. Tluckova, A.P. Testa Salmazo, C. Bernecky, (n.d.).
date_created: 2023-12-04T14:51:00Z
date_published: 2023-12-05T00:00:00Z
date_updated: 2023-12-05T10:37:28Z
day: '05'
ddc:
- '572'
department:
- _id: CaBe
doi: 10.15479/AT:ISTA:14644
file:
- access_level: open_access
  checksum: c45608cb97ee36d7b50ba518db8e07b0
  content_type: application/pdf
  creator: dernst
  date_created: 2023-12-05T10:37:02Z
  date_updated: 2023-12-05T10:37:02Z
  file_id: '14646'
  file_name: 2023_Tluckova_etal_REx.pdf
  file_size: 4892920
  relation: main_file
  success: 1
file_date_updated: 2023-12-05T10:37:02Z
has_accepted_license: '1'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Submitted Version
project:
- _id: c08a6700-5a5b-11eb-8a69-82a722b2bc30
  grant_number: P34185
  name: Regulation of mammalian transcription by noncoding RNA
publication_status: submitted
publisher: Institute of Science and Technology Austria
status: public
title: Mechanism of mammalian transcriptional repression by noncoding RNA
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: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2023'
...
---
_id: '14683'
abstract:
- lang: eng
  text: "Mosaic analysis with double markers (MADM) technology enables the generation
    of genetic mosaic tissue in mice and high-resolution phenotyping at the individual
    cell level. Here, we present a protocol for isolating MADM-labeled cells with
    high yield for downstream molecular analyses using fluorescence-activated cell
    sorting (FACS). We describe steps for generating MADM-labeled mice, perfusion,
    single-cell suspension, and debris removal. We then detail procedures for cell
    sorting by FACS and downstream analysis. This protocol is suitable for embryonic
    to adult mice.\r\nFor complete details on the use and execution of this protocol,
    please refer to Contreras et al. (2021).1"
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: This research was supported by the Scientific Service Units (SSU)
  at IST Austria through resources provided by the Imaging & Optics Facility (IOF)
  and Preclinical Facilities (PCF). N.A. received support from FWF Firnberg-Programme
  (T 1031). G.C. received support from the European Union’s Horizon 2020 research
  and innovation programme under the Marie Skłodowska-Curie grant agreement no. 754411
  as an ISTplus postdoctoral fellow. This work was also supported by IST Austria institutional
  funds, FWF SFB F78 to S.H., and the European Research Council (ERC) under the European
  Union’s Horizon 2020 research and innovation programme (grant agreement no. 725780
  LinPro) to S.H.
article_number: '102771'
article_processing_charge: No
article_type: review
author:
- first_name: Nicole
  full_name: Amberg, Nicole
  id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
  last_name: Amberg
  orcid: 0000-0002-3183-8207
- 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: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
citation:
  ama: Amberg N, Cheung GT, Hippenmeyer S. Protocol for sorting cells from mouse brains
    labeled with mosaic analysis with double markers by flow cytometry. <i>STAR Protocols</i>.
    2023;5(1). doi:<a href="https://doi.org/10.1016/j.xpro.2023.102771">10.1016/j.xpro.2023.102771</a>
  apa: Amberg, N., Cheung, G. T., &#38; Hippenmeyer, S. (2023). Protocol for sorting
    cells from mouse brains labeled with mosaic analysis with double markers by flow
    cytometry. <i>STAR Protocols</i>. Elsevier. <a href="https://doi.org/10.1016/j.xpro.2023.102771">https://doi.org/10.1016/j.xpro.2023.102771</a>
  chicago: Amberg, Nicole, Giselle T Cheung, and Simon Hippenmeyer. “Protocol for
    Sorting Cells from Mouse Brains Labeled with Mosaic Analysis with Double Markers
    by Flow Cytometry.” <i>STAR Protocols</i>. Elsevier, 2023. <a href="https://doi.org/10.1016/j.xpro.2023.102771">https://doi.org/10.1016/j.xpro.2023.102771</a>.
  ieee: N. Amberg, G. T. Cheung, and S. Hippenmeyer, “Protocol for sorting cells from
    mouse brains labeled with mosaic analysis with double markers by flow cytometry,”
    <i>STAR Protocols</i>, vol. 5, no. 1. Elsevier, 2023.
  ista: Amberg N, Cheung GT, Hippenmeyer S. 2023. Protocol for sorting cells from
    mouse brains labeled with mosaic analysis with double markers by flow cytometry.
    STAR Protocols. 5(1), 102771.
  mla: Amberg, Nicole, et al. “Protocol for Sorting Cells from Mouse Brains Labeled
    with Mosaic Analysis with Double Markers by Flow Cytometry.” <i>STAR Protocols</i>,
    vol. 5, no. 1, 102771, Elsevier, 2023, doi:<a href="https://doi.org/10.1016/j.xpro.2023.102771">10.1016/j.xpro.2023.102771</a>.
  short: N. Amberg, G.T. Cheung, S. Hippenmeyer, STAR Protocols 5 (2023).
date_created: 2023-12-13T11:48:05Z
date_published: 2023-12-08T00:00:00Z
date_updated: 2023-12-18T08:06:14Z
day: '08'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.xpro.2023.102771
ec_funded: 1
external_id:
  pmid:
  - '38070137'
intvolume: '         5'
issue: '1'
keyword:
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- General Neuroscience
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1016/j.xpro.2023.102771
month: '12'
oa: 1
oa_version: Submitted Version
pmid: 1
project:
- _id: 268F8446-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: T0101031
  name: Role of Eed in neural stem cell lineage progression
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
  grant_number: F07805
  name: Molecular Mechanisms of Neural Stem Cell Lineage Progression
- _id: 260018B0-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '725780'
  name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: STAR Protocols
publication_identifier:
  issn:
  - 2666-1667
publication_status: epub_ahead
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Protocol for sorting cells from mouse brains labeled with mosaic analysis with
  double markers by flow cytometry
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: 5
year: '2023'
...
---
_id: '13107'
abstract:
- lang: eng
  text: "Within the human body, the brain exhibits the highest rate of energy consumption
    amongst all organs, with the majority of generated ATP being utilized to sustain
    neuronal activity. Therefore, the metabolism of the mature cerebral cortex is
    geared towards preserving metabolic homeostasis whilst generating significant
    amounts of energy. This requires a precise interplay between diverse metabolic
    pathways, spanning from a tissue-wide scale to the level of individual neurons.
    Disturbances to this delicate metabolic equilibrium, such as those resulting from
    maternal malnutrition\r\nor mutations affecting metabolic enzymes, often result
    in neuropathological variants of neurodevelopment. For instance, mutations in
    SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs),
    have been associated with autism and microcephaly. However, despite recent progress
    in the field, the extent of metabolic restructuring that occurs within the developing
    brain and the corresponding alterations in nutrient demands during various critical
    periods remain largely unknown. To investigate this, we performed metabolomic
    profiling of the murine cerebral cortex to characterize the metabolic state of
    the forebrain at different developmental stages. We found that the developing
    cortex undergoes substantial metabolic reprogramming, with specific sets of metabolites
    displaying stage-specific changes. According to our observations, we determined
    a distinct temporal period in postnatal development during which the cortex displays
    heightened reliance on LNAAs. Hence, using a conditional knock-out mouse model,
    we deleted Slc7a5 in neural cells, allowing us to monitor the impact of a perturbed
    neuronal metabolic state across multiple developmental stages of corticogenesis.
    We found that manipulating the levels of essential LNAAs in cortical neurons in
    vivo affects one particular perinatal developmental period critical for cortical
    network refinement. Abnormally low intracellular LNAA levels result in cell-autonomous
    alterations in neuronal lipid metabolism, excitability, and survival during this
    particular time window. Although most of the effects of Slc7a5 deletion on neuronal
    physiology are transient, derailment of these processes during this brief but
    crucial window leads to long-term circuit dysfunction in mice. In conclusion,
    out data indicate that the cerebral cortex undergoes significant metabolic reorganization
    during development. This process involves the intricate integration of multiple
    metabolic pathways to ensure optimal neuronal function throughout different developmental
    stages. Our findings offer a paradigm for understanding how neurons synchronize
    the expression of nutrient-related genes with their activity to allow proper brain
    maturation. Further, our results demonstrate that disruptions in these precisely
    calibrated metabolic processes during critical periods of brain development may
    result in neuropathological outcomes in mice and in humans."
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: EM-Fac
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Lisa
  full_name: Knaus, Lisa
  id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
  last_name: Knaus
citation:
  ama: 'Knaus L. The metabolism of the developing brain : How large neutral amino
    acids modulate perinatal neuronal excitability and survival. 2023. doi:<a href="https://doi.org/10.15479/at:ista:13107">10.15479/at:ista:13107</a>'
  apa: 'Knaus, L. (2023). <i>The metabolism of the developing brain : How large neutral
    amino acids modulate perinatal neuronal excitability and survival</i>. Institute
    of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:13107">https://doi.org/10.15479/at:ista:13107</a>'
  chicago: 'Knaus, Lisa. “The Metabolism of the Developing Brain : How Large Neutral
    Amino Acids Modulate Perinatal Neuronal Excitability and Survival.” Institute
    of Science and Technology Austria, 2023. <a href="https://doi.org/10.15479/at:ista:13107">https://doi.org/10.15479/at:ista:13107</a>.'
  ieee: 'L. Knaus, “The metabolism of the developing brain : How large neutral amino
    acids modulate perinatal neuronal excitability and survival,” Institute of Science
    and Technology Austria, 2023.'
  ista: 'Knaus L. 2023. The metabolism of the developing brain : How large neutral
    amino acids modulate perinatal neuronal excitability and survival. Institute of
    Science and Technology Austria.'
  mla: 'Knaus, Lisa. <i>The Metabolism of the Developing Brain : How Large Neutral
    Amino Acids Modulate Perinatal Neuronal Excitability and Survival</i>. Institute
    of Science and Technology Austria, 2023, doi:<a href="https://doi.org/10.15479/at:ista:13107">10.15479/at:ista:13107</a>.'
  short: 'L. Knaus, The Metabolism of the Developing Brain : How Large Neutral Amino
    Acids Modulate Perinatal Neuronal Excitability and Survival, Institute of Science
    and Technology Austria, 2023.'
date_created: 2023-06-01T09:05:24Z
date_published: 2023-05-31T00:00:00Z
date_updated: 2024-02-07T08:03:33Z
day: '31'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: GaNo
doi: 10.15479/at:ista:13107
ec_funded: 1
file:
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  date_created: 2023-06-01T13:48:41Z
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file_date_updated: 2023-06-07T08:41:49Z
has_accepted_license: '1'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: '147'
project:
- _id: 25444568-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715508'
  name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
    and in vitro Models
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232-B24
  name: Molecular Drug Targets
publication_identifier:
  issn:
  - 2663 - 337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '12802'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
title: 'The metabolism of the developing brain : How large neutral amino acids modulate
  perinatal neuronal excitability and survival'
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2023'
...
---
_id: '13126'
abstract:
- lang: eng
  text: Mapping the complex and dense arrangement of cells and their connectivity
    in brain tissue demands nanoscale spatial resolution imaging. Super-resolution
    optical microscopy excels at visualizing specific molecules and individual cells
    but fails to provide tissue context. Here, we developed Comprehensive Analysis
    of Tissues across Scales (CATS), a technology to densely map brain tissue architecture
    from millimeter regional to nanometer synaptic scales in diverse chemically fixed
    brain preparations, including rodent and human. CATS uses fixation-compatible
    extracellular labeling and optical imaging, including stimulated emission depletion
    or expansion microscopy, to comprehensively delineate cellular structures. It
    enables three-dimensional reconstruction of single synapses and mapping of synaptic
    connectivity by identification and analysis of putative synaptic cleft regions.
    Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed
    and quantified the synaptic input and output structure of identified neurons.
    We furthermore demonstrate applicability to clinically derived human tissue samples,
    including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing
    the cellular architecture of brain tissue in health and disease.
acknowledged_ssus:
- _id: ScienComp
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
- _id: E-Lib
acknowledgement: "We thank Jakob Vorlaufer, Nathalie Agudelo-Dueñas, Wiebke Jahr,
  Andreas Wartak for microscope maintenance and troubleshooting, Caroline Kreuzinger,
  Anna Freeman, and Irene Erber for technical assistance and Matthias Tomschik for
  support with obtaining human samples. We gratefully acknowledge Eder Miguel for
  setting up webKnossos and Marek Šuplata for computational support and hardware control.
  We are grateful to Ryuichi Shigemoto and Bernd Bickel for generous support, and
  Michael Sixt and Scott Boyd (Stanford University) for discussions and critical reading
  of the manuscript. PSD95-HaloTag mice were kindly provided by Seth Grant (University
  of Edinburgh). We acknowledge expert support by IST Austria’s scientific computing,
  imaging and optics, preclinical, and lab support facilities, and by the Library
  and Miba machine shop.\r\nWe gratefully acknowledge funding by the following sources:
  \r\nAustrian Science Fund (FWF) grant I3600-B27 (JGD)\r\nAustrian Science Fund (FWF)
  grant DK W1232 (JGD, JMM)\r\nAustrian Science Fund (FWF) grant Z 312-B27, Wittgenstein
  award (PJ)\r\nAustrian Science Funds (FWF) projects I4685-B, I6565-B (SYNABS) and
  DOC 33-B27 (RH)\r\nGesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022
  (JGD)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European
  Research Council (ERC) grant 715508 – REVERSEAUTISM (GN)\r\nEuropean Union’s Horizon
  2020 research and innovation programme, European Research Council (ERC) grant 692692
  – GIANTSYN (PJ)\r\nMarie Skłodowska-Curie Actions Fellowship GA no. 665385 under
  the EU Horizon 2020 program (JMM, JL)\r\nMarie Skłodowska-Curie Actions Individual
  Fellowship 101026635 under the EU Horizon 2020 program (JFW)"
article_processing_charge: No
author:
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
citation:
  ama: Danzl JG. Research data for the publication “Imaging brain tissue architecture
    across millimeter to nanometer scales.” 2023. doi:<a href="https://doi.org/10.15479/AT:ISTA:13126">10.15479/AT:ISTA:13126</a>
  apa: Danzl, J. G. (2023). Research data for the publication “Imaging brain tissue
    architecture across millimeter to nanometer scales.” Institute of Science and
    Technology Austria. <a href="https://doi.org/10.15479/AT:ISTA:13126">https://doi.org/10.15479/AT:ISTA:13126</a>
  chicago: Danzl, Johann G. “Research Data for the Publication ‘Imaging Brain Tissue
    Architecture across Millimeter to Nanometer Scales.’” Institute of Science and
    Technology Austria, 2023. <a href="https://doi.org/10.15479/AT:ISTA:13126">https://doi.org/10.15479/AT:ISTA:13126</a>.
  ieee: J. G. Danzl, “Research data for the publication ‘Imaging brain tissue architecture
    across millimeter to nanometer scales.’” Institute of Science and Technology Austria,
    2023.
  ista: Danzl JG. 2023. Research data for the publication ‘Imaging brain tissue architecture
    across millimeter to nanometer scales’, Institute of Science and Technology Austria,
    <a href="https://doi.org/10.15479/AT:ISTA:13126">10.15479/AT:ISTA:13126</a>.
  mla: Danzl, Johann G. <i>Research Data for the Publication “Imaging Brain Tissue
    Architecture across Millimeter to Nanometer Scales.”</i> Institute of Science
    and Technology Austria, 2023, doi:<a href="https://doi.org/10.15479/AT:ISTA:13126">10.15479/AT:ISTA:13126</a>.
  short: J.G. Danzl, (2023).
contributor:
- first_name: Julia M
  id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
  last_name: Michalska
- first_name: Julia
  id: 46E28B80-F248-11E8-B48F-1D18A9856A87
  last_name: Lyudchik
- first_name: Philipp
  id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
  last_name: Velicky
  orcid: 0000-0002-2340-7431
- first_name: Hana
  id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed
  last_name: Stefanickova
- first_name: Jake
  id: 63836096-4690-11EA-BD4E-32803DDC885E
  last_name: Watson
  orcid: 0000-0002-8698-3823
- first_name: Alban
  id: 9ac8f577-2357-11eb-997a-e566c5550886
  last_name: Cenameri
- first_name: Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Nicole
  id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
  last_name: Amberg
  orcid: 0000-0002-3183-8207
- first_name: Alessandro
  id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
  last_name: Venturino
  orcid: 0000-0003-2356-9403
- first_name: Karl
  last_name: Roessler
- first_name: Thomas
  last_name: Czech
- first_name: Romana
  last_name: Höftberger
- first_name: Sandra
  id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
  last_name: Siegert
  orcid: 0000-0001-8635-0877
- first_name: Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
date_created: 2023-06-07T07:15:12Z
date_published: 2023-08-04T00:00:00Z
date_updated: 2024-02-21T12:18:19Z
day: '04'
ddc:
- '610'
department:
- _id: JoDa
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: Bio
- _id: RySh
doi: 10.15479/AT:ISTA:13126
ec_funded: 1
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oa_version: Published Version
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: I03600
  name: Optical control of synaptic function via adhesion molecules
- _id: 26AA4EF2-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232-B24
  name: Molecular Drug Targets
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z00312
  name: The Wittgenstein Prize
- _id: 23889792-32DE-11EA-91FC-C7463DDC885E
  name: High content imaging to decode human immune cell interactions in health and
    allergic disease
- _id: 25444568-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715508'
  name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
    and in vitro Models
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
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  call_identifier: H2020
  grant_number: '101026635'
  name: Synaptic computations of the hippocampal CA3 circuitry
publisher: Institute of Science and Technology Austria
related_material:
  link:
  - description: 'Original data for Fig. 5d, Fig. 5d (N2V) and Fig. 5f-i, provided
      via an external link due to the large size (>10GB) of the datasets. '
    relation: research_data
    url: https://pub.ista.ac.at/group_danzl/data/CATS/
  record:
  - id: '14257'
    relation: used_in_publication
    status: public
status: public
title: Research data for the publication "Imaging brain tissue architecture across
  millimeter to nanometer scales"
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: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2023'
...
---
_id: '13267'
abstract:
- lang: eng
  text: Three-dimensional (3D) reconstruction of living brain tissue down to an individual
    synapse level would create opportunities for decoding the dynamics and structure–function
    relationships of the brain’s complex and dense information processing network;
    however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise
    ratio and prohibitive light burden in optical imaging, whereas electron microscopy
    is inherently static. Here we solved these challenges by developing an integrated
    optical/machine-learning technology, LIONESS (live information-optimized nanoscopy
    enabling saturated segmentation). This leverages optical modifications to stimulated
    emission depletion microscopy in comprehensively, extracellularly labeled tissue
    and previous information on sample structure via machine learning to simultaneously
    achieve isotropic super-resolution, high signal-to-noise ratio and compatibility
    with living tissue. This allows dense deep-learning-based instance segmentation
    and 3D reconstruction at a synapse level, incorporating molecular, activity and
    morphodynamic information. LIONESS opens up avenues for studying the dynamic functional
    (nano-)architecture of living brain tissue.
acknowledged_ssus:
- _id: ScienComp
- _id: Bio
- _id: PreCl
- _id: E-Lib
- _id: LifeSc
- _id: M-Shop
acknowledgement: "We thank J. Vorlaufer, N. Agudelo and A. Wartak for microscope maintenance
  and troubleshooting, C. Kreuzinger and A. Freeman for technical assistance, M. Šuplata
  for hardware control support and M. Cunha dos Santos for initial exploration of
  software. We\r\nthank P. Henderson for advice on deep-learning training and M. Sixt,
  S. Boyd and T. Weiss for discussions and critical reading of the manuscript. L.
  Lavis (Janelia Research Campus) generously provided the JF585-HaloTag ligand. We
  acknowledge expert support by IST\r\nAustria’s scientific computing, imaging and
  optics, preclinical, library and laboratory support facilities and by the Miba machine
  shop. We gratefully acknowledge funding by the following sources: Austrian Science
  Fund (F.W.F.) grant no. I3600-B27 (J.G.D.), grant no. DK W1232\r\n(J.G.D. and J.M.M.)
  and grant no. Z 312-B27, Wittgenstein award (P.J.); the Gesellschaft für Forschungsförderung
  NÖ grant no. LSC18-022 (J.G.D.); an ISTA Interdisciplinary project grant (J.G.D.
  and B.B.); the European Union’s Horizon 2020 research and innovation programme,\r\nMarie-Skłodowska
  Curie grant 665385 (J.M.M. and J.L.); the European Union’s Horizon 2020 research
  and innovation programme, European Research Council grant no. 715767, MATERIALIZABLE
  (B.B.); grant no. 715508, REVERSEAUTISM (G.N.); grant no. 695568, SYNNOVATE (S.G.N.G.);
  and grant no. 692692, GIANTSYN (P.J.); the Simons\r\nFoundation Autism Research
  Initiative grant no. 529085 (S.G.N.G.); the Wellcome Trust Technology Development
  grant no. 202932 (S.G.N.G.); the Marie Skłodowska-Curie Actions Individual Fellowship
  no. 101026635 under the EU Horizon 2020 program (J.F.W.);\r\nthe Human Frontier
  Science Program postdoctoral fellowship LT000557/2018 (W.J.); and the National Science
  Foundation grant no. IIS-1835231 (H.P.) and NCS-FO-2124179 (H.P.)."
article_processing_charge: Yes
article_type: original
author:
- first_name: Philipp
  full_name: Velicky, Philipp
  id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
  last_name: Velicky
  orcid: 0000-0002-2340-7431
- first_name: Eder
  full_name: Miguel Villalba, Eder
  id: 3FB91342-F248-11E8-B48F-1D18A9856A87
  last_name: Miguel Villalba
  orcid: 0000-0001-5665-0430
- first_name: Julia M
  full_name: Michalska, Julia M
  id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
  last_name: Michalska
  orcid: 0000-0003-3862-1235
- first_name: Julia
  full_name: Lyudchik, Julia
  id: 46E28B80-F248-11E8-B48F-1D18A9856A87
  last_name: Lyudchik
- first_name: Donglai
  full_name: Wei, Donglai
  last_name: Wei
- first_name: Zudi
  full_name: Lin, Zudi
  last_name: Lin
- first_name: Jake
  full_name: Watson, Jake
  id: 63836096-4690-11EA-BD4E-32803DDC885E
  last_name: Watson
  orcid: 0000-0002-8698-3823
- first_name: Jakob
  full_name: Troidl, Jakob
  last_name: Troidl
- first_name: Johanna
  full_name: Beyer, Johanna
  last_name: Beyer
- first_name: Yoav
  full_name: Ben Simon, Yoav
  id: 43DF3136-F248-11E8-B48F-1D18A9856A87
  last_name: Ben Simon
- 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: Wiebke
  full_name: Jahr, Wiebke
  id: 425C1CE8-F248-11E8-B48F-1D18A9856A87
  last_name: Jahr
- first_name: Alban
  full_name: Cenameri, Alban
  id: 9ac8f577-2357-11eb-997a-e566c5550886
  last_name: Cenameri
- first_name: Johannes
  full_name: Broichhagen, Johannes
  last_name: Broichhagen
- first_name: Seth G.N.
  full_name: Grant, Seth G.N.
  last_name: Grant
- 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: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Hanspeter
  full_name: Pfister, Hanspeter
  last_name: Pfister
- first_name: Bernd
  full_name: Bickel, Bernd
  id: 49876194-F248-11E8-B48F-1D18A9856A87
  last_name: Bickel
  orcid: 0000-0001-6511-9385
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
citation:
  ama: Velicky P, Miguel Villalba E, Michalska JM, et al. Dense 4D nanoscale reconstruction
    of living brain tissue. <i>Nature Methods</i>. 2023;20:1256-1265. doi:<a href="https://doi.org/10.1038/s41592-023-01936-6">10.1038/s41592-023-01936-6</a>
  apa: Velicky, P., Miguel Villalba, E., Michalska, J. M., Lyudchik, J., Wei, D.,
    Lin, Z., … Danzl, J. G. (2023). Dense 4D nanoscale reconstruction of living brain
    tissue. <i>Nature Methods</i>. Springer Nature. <a href="https://doi.org/10.1038/s41592-023-01936-6">https://doi.org/10.1038/s41592-023-01936-6</a>
  chicago: Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Julia Lyudchik,
    Donglai Wei, Zudi Lin, Jake Watson, et al. “Dense 4D Nanoscale Reconstruction
    of Living Brain Tissue.” <i>Nature Methods</i>. Springer Nature, 2023. <a href="https://doi.org/10.1038/s41592-023-01936-6">https://doi.org/10.1038/s41592-023-01936-6</a>.
  ieee: P. Velicky <i>et al.</i>, “Dense 4D nanoscale reconstruction of living brain
    tissue,” <i>Nature Methods</i>, vol. 20. Springer Nature, pp. 1256–1265, 2023.
  ista: Velicky P, Miguel Villalba E, Michalska JM, Lyudchik J, Wei D, Lin Z, Watson
    J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen
    J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. 2023. Dense
    4D nanoscale reconstruction of living brain tissue. Nature Methods. 20, 1256–1265.
  mla: Velicky, Philipp, et al. “Dense 4D Nanoscale Reconstruction of Living Brain
    Tissue.” <i>Nature Methods</i>, vol. 20, Springer Nature, 2023, pp. 1256–65, doi:<a
    href="https://doi.org/10.1038/s41592-023-01936-6">10.1038/s41592-023-01936-6</a>.
  short: P. Velicky, E. Miguel Villalba, J.M. Michalska, J. Lyudchik, D. Wei, Z. Lin,
    J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri,
    J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel,
    J.G. Danzl, Nature Methods 20 (2023) 1256–1265.
date_created: 2023-07-23T22:01:13Z
date_published: 2023-08-01T00:00:00Z
date_updated: 2024-01-10T08:37:48Z
day: '01'
department:
- _id: PeJo
- _id: GaNo
- _id: BeBi
- _id: JoDa
- _id: Bio
doi: 10.1038/s41592-023-01936-6
ec_funded: 1
external_id:
  isi:
  - '001025621500001'
  pmid:
  - '37429995'
intvolume: '        20'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1038/s41592-023-01936-6
month: '08'
oa: 1
oa_version: Published Version
page: 1256-1265
pmid: 1
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: I03600
  name: Optical control of synaptic function via adhesion molecules
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232-B24
  name: Molecular Drug Targets
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z00312
  name: The Wittgenstein Prize
- _id: 23889792-32DE-11EA-91FC-C7463DDC885E
  name: High content imaging to decode human immune cell interactions in health and
    allergic disease
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 24F9549A-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715767'
  name: 'MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and
    Modeling'
- _id: 25444568-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715508'
  name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
    and in vitro Models
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
  call_identifier: H2020
  grant_number: '101026635'
  name: Synaptic computations of the hippocampal CA3 circuitry
- _id: 2668BFA0-B435-11E9-9278-68D0E5697425
  grant_number: LT00057
  name: High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration
publication: Nature Methods
publication_identifier:
  eissn:
  - 1548-7105
  issn:
  - 1548-7091
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - relation: software
    url: https://github.com/danzllab/LIONESS
  record:
  - id: '12817'
    relation: research_data
    status: public
  - id: '14770'
    relation: shorter_version
    status: public
scopus_import: '1'
status: public
title: Dense 4D nanoscale reconstruction of living brain tissue
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 20
year: '2023'
...
---
_id: '14082'
abstract:
- lang: eng
  text: Epithelial barrier function is commonly analyzed using transepithelial electrical
    resistance, which measures ion flux across a monolayer, or by adding traceable
    macromolecules and monitoring their passage across the monolayer. Although these
    methods measure changes in global barrier function, they lack the sensitivity
    needed to detect local or transient barrier breaches, and they do not reveal the
    location of barrier leaks. Therefore, we previously developed a method that we
    named the zinc-based ultrasensitive microscopic barrier assay (ZnUMBA), which
    overcomes these limitations, allowing for detection of local tight junction leaks
    with high spatiotemporal resolution. Here, we present expanded applications for
    ZnUMBA. ZnUMBA can be used in Xenopus embryos to measure the dynamics of barrier
    restoration and actin accumulation following laser injury. ZnUMBA can also be
    effectively utilized in developing zebrafish embryos as well as cultured monolayers
    of Madin–Darby canine kidney (MDCK) II epithelial cells. ZnUMBA is a powerful
    and flexible method that, with minimal optimization, can be applied to multiple
    systems to measure dynamic changes in barrier function with spatiotemporal precision.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
acknowledgement: "The authors thank their respective lab members for feedback and
  helpful discussions. We thank the bioimaging and zebrafish facilities of IST Austria
  for their support.\r\nThis work was supported by the National Institutes of Health
  [R01GM112794 to A.L.M.], by Grants-in-Aid for Scientific Research from the Japan
  Society for the Promotion of Science [21K06156 to T.H.], by the Grant Program for
  Biomedical Engineering Research from the Nakatani Foundation for Advancement of
  Measuring Technologies in Biomedical Engineering [to T.H.] and by funding from the
  European Research Council [advanced grant 742573 to C.-P.H.]. "
article_number: jcs260668
article_processing_charge: No
article_type: original
author:
- first_name: Tomohito
  full_name: Higashi, Tomohito
  last_name: Higashi
- first_name: Rachel E.
  full_name: Stephenson, Rachel E.
  last_name: Stephenson
- first_name: Cornelia
  full_name: Schwayer, Cornelia
  id: 3436488C-F248-11E8-B48F-1D18A9856A87
  last_name: Schwayer
  orcid: 0000-0001-5130-2226
- first_name: Karla
  full_name: Huljev, Karla
  id: 44C6F6A6-F248-11E8-B48F-1D18A9856A87
  last_name: Huljev
- first_name: Atsuko Y.
  full_name: Higashi, Atsuko Y.
  last_name: Higashi
- first_name: Carl-Philipp J
  full_name: Heisenberg, Carl-Philipp J
  id: 39427864-F248-11E8-B48F-1D18A9856A87
  last_name: Heisenberg
  orcid: 0000-0002-0912-4566
- first_name: Hideki
  full_name: Chiba, Hideki
  last_name: Chiba
- first_name: Ann L.
  full_name: Miller, Ann L.
  last_name: Miller
citation:
  ama: Higashi T, Stephenson RE, Schwayer C, et al. ZnUMBA - a live imaging method
    to detect local barrier breaches. <i>Journal of Cell Science</i>. 2023;136(15).
    doi:<a href="https://doi.org/10.1242/jcs.260668">10.1242/jcs.260668</a>
  apa: Higashi, T., Stephenson, R. E., Schwayer, C., Huljev, K., Higashi, A. Y., Heisenberg,
    C.-P. J., … Miller, A. L. (2023). ZnUMBA - a live imaging method to detect local
    barrier breaches. <i>Journal of Cell Science</i>. The Company of Biologists. <a
    href="https://doi.org/10.1242/jcs.260668">https://doi.org/10.1242/jcs.260668</a>
  chicago: Higashi, Tomohito, Rachel E. Stephenson, Cornelia Schwayer, Karla Huljev,
    Atsuko Y. Higashi, Carl-Philipp J Heisenberg, Hideki Chiba, and Ann L. Miller.
    “ZnUMBA - a Live Imaging Method to Detect Local Barrier Breaches.” <i>Journal
    of Cell Science</i>. The Company of Biologists, 2023. <a href="https://doi.org/10.1242/jcs.260668">https://doi.org/10.1242/jcs.260668</a>.
  ieee: T. Higashi <i>et al.</i>, “ZnUMBA - a live imaging method to detect local
    barrier breaches,” <i>Journal of Cell Science</i>, vol. 136, no. 15. The Company
    of Biologists, 2023.
  ista: Higashi T, Stephenson RE, Schwayer C, Huljev K, Higashi AY, Heisenberg C-PJ,
    Chiba H, Miller AL. 2023. ZnUMBA - a live imaging method to detect local barrier
    breaches. Journal of Cell Science. 136(15), jcs260668.
  mla: Higashi, Tomohito, et al. “ZnUMBA - a Live Imaging Method to Detect Local Barrier
    Breaches.” <i>Journal of Cell Science</i>, vol. 136, no. 15, jcs260668, The Company
    of Biologists, 2023, doi:<a href="https://doi.org/10.1242/jcs.260668">10.1242/jcs.260668</a>.
  short: T. Higashi, R.E. Stephenson, C. Schwayer, K. Huljev, A.Y. Higashi, C.-P.J.
    Heisenberg, H. Chiba, A.L. Miller, Journal of Cell Science 136 (2023).
date_created: 2023-08-20T22:01:13Z
date_published: 2023-08-01T00:00:00Z
date_updated: 2023-12-13T12:11:18Z
day: '01'
ddc:
- '570'
department:
- _id: CaHe
- _id: EvBe
doi: 10.1242/jcs.260668
ec_funded: 1
external_id:
  isi:
  - '001070149000001'
file:
- access_level: closed
  checksum: a399389b7e3d072f1788b63e612a10b3
  content_type: application/pdf
  creator: dernst
  date_created: 2023-08-21T07:37:54Z
  date_updated: 2023-08-21T07:37:54Z
  embargo: 2024-08-10
  embargo_to: open_access
  file_id: '14092'
  file_name: 2023_JourCellScience_Higashi.pdf
  file_size: 18665315
  relation: main_file
file_date_updated: 2023-08-21T07:37:54Z
has_accepted_license: '1'
intvolume: '       136'
isi: 1
issue: '15'
language:
- iso: eng
month: '08'
oa_version: None
project:
- _id: 260F1432-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '742573'
  name: Interaction and feedback between cell mechanics and fate specification in
    vertebrate gastrulation
publication: Journal of Cell Science
publication_identifier:
  eissn:
  - 1477-9137
  issn:
  - 0021-9533
publication_status: published
publisher: The Company of Biologists
quality_controlled: '1'
scopus_import: '1'
status: public
title: ZnUMBA - a live imaging method to detect local barrier breaches
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 136
year: '2023'
...
---
_id: '14257'
abstract:
- lang: eng
  text: Mapping the complex and dense arrangement of cells and their connectivity
    in brain tissue demands nanoscale spatial resolution imaging. Super-resolution
    optical microscopy excels at visualizing specific molecules and individual cells
    but fails to provide tissue context. Here we developed Comprehensive Analysis
    of Tissues across Scales (CATS), a technology to densely map brain tissue architecture
    from millimeter regional to nanometer synaptic scales in diverse chemically fixed
    brain preparations, including rodent and human. CATS uses fixation-compatible
    extracellular labeling and optical imaging, including stimulated emission depletion
    or expansion microscopy, to comprehensively delineate cellular structures. It
    enables three-dimensional reconstruction of single synapses and mapping of synaptic
    connectivity by identification and analysis of putative synaptic cleft regions.
    Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed
    and quantified the synaptic input and output structure of identified neurons.
    We furthermore demonstrate applicability to clinically derived human tissue samples,
    including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing
    the cellular architecture of brain tissue in health and disease.
acknowledged_ssus:
- _id: ScienComp
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
- _id: E-Lib
acknowledgement: 'We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak
  for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I.
  Erber for technical assistance; and M. Tomschik for support with obtaining human
  samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata
  for computational support and hardware control. We are grateful to R. Shigemoto
  and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University)
  for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly
  provided by S. Grant (University of Edinburgh). We acknowledge expert support by
  Institute of Science and Technology Austria’s scientific computing, imaging and
  optics, preclinical and lab support facilities and by the Miba machine shop and
  library. We gratefully acknowledge funding by the following sources: Austrian Science
  Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232
  (J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award
  (P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27
  (R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.);
  European Union’s Horizon 2020 research and innovation programme, European Research
  Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020
  research and innovation programme, European Research Council (ERC) grant 692692
  – GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under
  the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions
  Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).'
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Julia M
  full_name: Michalska, Julia M
  id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
  last_name: Michalska
  orcid: 0000-0003-3862-1235
- first_name: Julia
  full_name: Lyudchik, Julia
  id: 46E28B80-F248-11E8-B48F-1D18A9856A87
  last_name: Lyudchik
- first_name: Philipp
  full_name: Velicky, Philipp
  id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
  last_name: Velicky
  orcid: 0000-0002-2340-7431
- first_name: Hana
  full_name: Korinkova, Hana
  id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed
  last_name: Korinkova
- first_name: Jake
  full_name: Watson, Jake
  id: 63836096-4690-11EA-BD4E-32803DDC885E
  last_name: Watson
  orcid: 0000-0002-8698-3823
- first_name: Alban
  full_name: Cenameri, Alban
  id: 9ac8f577-2357-11eb-997a-e566c5550886
  last_name: Cenameri
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Nicole
  full_name: Amberg, Nicole
  id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
  last_name: Amberg
  orcid: 0000-0002-3183-8207
- first_name: Alessandro
  full_name: Venturino, Alessandro
  id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
  last_name: Venturino
  orcid: 0000-0003-2356-9403
- first_name: Karl
  full_name: Roessler, Karl
  last_name: Roessler
- first_name: Thomas
  full_name: Czech, Thomas
  last_name: Czech
- first_name: Romana
  full_name: Höftberger, Romana
  last_name: Höftberger
- first_name: Sandra
  full_name: Siegert, Sandra
  id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
  last_name: Siegert
  orcid: 0000-0001-8635-0877
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
citation:
  ama: Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture
    across millimeter to nanometer scales. <i>Nature Biotechnology</i>. 2023. doi:<a
    href="https://doi.org/10.1038/s41587-023-01911-8">10.1038/s41587-023-01911-8</a>
  apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri,
    A., … Danzl, J. G. (2023). Imaging brain tissue architecture across millimeter
    to nanometer scales. <i>Nature Biotechnology</i>. Springer Nature. <a href="https://doi.org/10.1038/s41587-023-01911-8">https://doi.org/10.1038/s41587-023-01911-8</a>
  chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake
    Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture
    across Millimeter to Nanometer Scales.” <i>Nature Biotechnology</i>. Springer
    Nature, 2023. <a href="https://doi.org/10.1038/s41587-023-01911-8">https://doi.org/10.1038/s41587-023-01911-8</a>.
  ieee: J. M. Michalska <i>et al.</i>, “Imaging brain tissue architecture across millimeter
    to nanometer scales,” <i>Nature Biotechnology</i>. Springer Nature, 2023.
  ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer
    CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino
    G, Jonas PM, Danzl JG. 2023. Imaging brain tissue architecture across millimeter
    to nanometer scales. Nature Biotechnology.
  mla: Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter
    to Nanometer Scales.” <i>Nature Biotechnology</i>, Springer Nature, 2023, doi:<a
    href="https://doi.org/10.1038/s41587-023-01911-8">10.1038/s41587-023-01911-8</a>.
  short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri,
    C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S.
    Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology (2023).
date_created: 2023-09-03T22:01:15Z
date_published: 2023-08-31T00:00:00Z
date_updated: 2024-02-21T12:18:18Z
day: '31'
department:
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: JoDa
- _id: Bio
- _id: RySh
doi: 10.1038/s41587-023-01911-8
ec_funded: 1
external_id:
  isi:
  - '001065254200001'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1038/s41587-023-01911-8
month: '08'
oa: 1
oa_version: Published Version
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: I03600
  name: Optical control of synaptic function via adhesion molecules
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232-B24
  name: Molecular Drug Targets
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z00312
  name: The Wittgenstein Prize
- _id: 23889792-32DE-11EA-91FC-C7463DDC885E
  name: High content imaging to decode human immune cell interactions in health and
    allergic disease
- _id: 25444568-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715508'
  name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
    and in vitro Models
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
  call_identifier: H2020
  grant_number: '101026635'
  name: Synaptic computations of the hippocampal CA3 circuitry
publication: Nature Biotechnology
publication_identifier:
  eissn:
  - 1546-1696
  issn:
  - 1087-0156
publication_status: epub_ahead
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - relation: software
    url: https://github.com/danzllab/CATS
  record:
  - id: '13126'
    relation: research_data
    status: public
scopus_import: '1'
status: public
title: Imaging brain tissue architecture across millimeter to nanometer scales
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2023'
...
---
_id: '12349'
abstract:
- lang: eng
  text: Statistics of natural scenes are not uniform - their structure varies dramatically
    from ground to sky. It remains unknown whether these non-uniformities are reflected
    in the large-scale organization of the early visual system and what benefits such
    adaptations would confer. Here, by relying on the efficient coding hypothesis,
    we predict that changes in the structure of receptive fields across visual space
    increase the efficiency of sensory coding. We show experimentally that, in agreement
    with our predictions, receptive fields of retinal ganglion cells change their
    shape along the dorsoventral retinal axis, with a marked surround asymmetry at
    the visual horizon. Our work demonstrates that, according to principles of efficient
    coding, the panoramic structure of natural scenes is exploited by the retina across
    space and cell-types.
acknowledged_ssus:
- _id: ScienComp
- _id: PreCl
- _id: LifeSc
- _id: Bio
acknowledgement: We thank Hiroki Asari for sharing the dataset of naturalistic images,
  Anton Sumser for sharing visual stimulus code, Yoav Ben Simon for initial explorative
  work with the generation of AAVs, and Tomas Vega-Zuñiga for help with immunostainings.
  We also thank Gasper Tkacik and members of the Neuroethology group for their comments
  on the manuscript. This research was supported by the Scientific Service Units of
  IST Austria through resources provided by Scientific Computing, the Preclinical
  Facility, the Lab Support Facility, and the Imaging and Optics Facility. This work
  was supported by European Union Horizon 2020 Marie Skłodowska-Curie grant 665385
  (DG), Austrian Science Fund (FWF) stand-alone grant P 34015 (WM), Human Frontiers
  Science Program LT000256/2018-L (AS), EMBO ALTF 1098-2017 (AS) and the European
  Research Council Starting Grant 756502 (MJ).
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Divyansh
  full_name: Gupta, Divyansh
  id: 2A485EBE-F248-11E8-B48F-1D18A9856A87
  last_name: Gupta
  orcid: 0000-0001-7400-6665
- first_name: Wiktor F
  full_name: Mlynarski, Wiktor F
  id: 358A453A-F248-11E8-B48F-1D18A9856A87
  last_name: Mlynarski
- 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: Jan
  full_name: Svaton, Jan
  id: f7f724c3-9d6f-11ed-9f44-e5c5f3a5bee2
  last_name: Svaton
  orcid: 0000-0002-6198-2939
- 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: Gupta D, Mlynarski WF, Sumser AL, Symonova O, Svaton J, Jösch MA. Panoramic
    visual statistics shape retina-wide organization of receptive fields. <i>Nature
    Neuroscience</i>. 2023;26:606-614. doi:<a href="https://doi.org/10.1038/s41593-023-01280-0">10.1038/s41593-023-01280-0</a>
  apa: Gupta, D., Mlynarski, W. F., Sumser, A. L., Symonova, O., Svaton, J., &#38;
    Jösch, M. A. (2023). Panoramic visual statistics shape retina-wide organization
    of receptive fields. <i>Nature Neuroscience</i>. Springer Nature. <a href="https://doi.org/10.1038/s41593-023-01280-0">https://doi.org/10.1038/s41593-023-01280-0</a>
  chicago: Gupta, Divyansh, Wiktor F Mlynarski, Anton L Sumser, Olga Symonova, Jan
    Svaton, and Maximilian A Jösch. “Panoramic Visual Statistics Shape Retina-Wide
    Organization of Receptive Fields.” <i>Nature Neuroscience</i>. Springer Nature,
    2023. <a href="https://doi.org/10.1038/s41593-023-01280-0">https://doi.org/10.1038/s41593-023-01280-0</a>.
  ieee: D. Gupta, W. F. Mlynarski, A. L. Sumser, O. Symonova, J. Svaton, and M. A.
    Jösch, “Panoramic visual statistics shape retina-wide organization of receptive
    fields,” <i>Nature Neuroscience</i>, vol. 26. Springer Nature, pp. 606–614, 2023.
  ista: Gupta D, Mlynarski WF, Sumser AL, Symonova O, Svaton J, Jösch MA. 2023. Panoramic
    visual statistics shape retina-wide organization of receptive fields. Nature Neuroscience.
    26, 606–614.
  mla: Gupta, Divyansh, et al. “Panoramic Visual Statistics Shape Retina-Wide Organization
    of Receptive Fields.” <i>Nature Neuroscience</i>, vol. 26, Springer Nature, 2023,
    pp. 606–14, doi:<a href="https://doi.org/10.1038/s41593-023-01280-0">10.1038/s41593-023-01280-0</a>.
  short: D. Gupta, W.F. Mlynarski, A.L. Sumser, O. Symonova, J. Svaton, M.A. Jösch,
    Nature Neuroscience 26 (2023) 606–614.
date_created: 2023-01-23T14:14:19Z
date_published: 2023-04-01T00:00:00Z
date_updated: 2023-10-04T11:41:05Z
day: '01'
ddc:
- '570'
department:
- _id: GradSch
- _id: MaJö
doi: 10.1038/s41593-023-01280-0
ec_funded: 1
external_id:
  isi:
  - '000955258300002'
  pmid:
  - '36959418'
file:
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  checksum: a33d91e398e548f34003170e10988368
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month: '04'
oa: 1
oa_version: Published Version
page: 606-614
pmid: 1
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 626c45b5-2b32-11ec-9570-e509828c1ba6
  grant_number: P34015
  name: Efficient coding with biophysical realism
- _id: 2634E9D2-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '756502'
  name: Circuits of Visual Attention
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  grant_number: LT000256
  name: Neuronal networks of salience and spatial detection in the murine superior
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- _id: 264FEA02-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 1098-2017
  name: Connecting sensory with motor processing in the superior colliculus
publication: Nature Neuroscience
publication_identifier:
  eissn:
  - 1546-1726
  issn:
  - 1097-6256
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  record:
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    relation: research_data
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scopus_import: '1'
status: public
title: Panoramic visual statistics shape retina-wide organization of receptive fields
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: 26
year: '2023'
...
---
_id: '12370'
abstract:
- lang: eng
  text: 'Statistics of natural scenes are not uniform - their structure varies dramatically
    from ground to sky. It remains unknown whether these non-uniformities are reflected
    in the large-scale organization of the early visual system and what benefits such
    adaptations would confer. Here, by relying on the efficient coding hypothesis,
    we predict that changes in the structure of receptive fields across visual space
    increase the efficiency of sensory coding. We show experimentally that, in agreement
    with our predictions, receptive fields of retinal ganglion cells change their
    shape along the dorsoventral retinal axis, with a marked surround asymmetry at
    the visual horizon. Our work demonstrates that, according to principles of efficient
    coding, the panoramic structure of natural scenes is exploited by the retina across
    space and cell-types. '
acknowledged_ssus:
- _id: ScienComp
- _id: M-Shop
- _id: Bio
- _id: PreCl
- _id: LifeSc
article_processing_charge: No
author:
- first_name: Divyansh
  full_name: Gupta, Divyansh
  id: 2A485EBE-F248-11E8-B48F-1D18A9856A87
  last_name: Gupta
  orcid: 0000-0001-7400-6665
- 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: Maximilian A
  full_name: Jösch, Maximilian A
  id: 2BD278E6-F248-11E8-B48F-1D18A9856A87
  last_name: Jösch
  orcid: 0000-0002-3937-1330
citation:
  ama: 'Gupta D, Sumser AL, Jösch MA. Research Data for: Panoramic visual statistics
    shape retina-wide organization of receptive fields. 2023. doi:<a href="https://doi.org/10.15479/AT:ISTA:12370">10.15479/AT:ISTA:12370</a>'
  apa: 'Gupta, D., Sumser, A. L., &#38; Jösch, M. A. (2023). Research Data for: Panoramic
    visual statistics shape retina-wide organization of receptive fields. Institute
    of Science and Technology Austria. <a href="https://doi.org/10.15479/AT:ISTA:12370">https://doi.org/10.15479/AT:ISTA:12370</a>'
  chicago: 'Gupta, Divyansh, Anton L Sumser, and Maximilian A Jösch. “Research Data
    for: Panoramic Visual Statistics Shape Retina-Wide Organization of Receptive Fields.”
    Institute of Science and Technology Austria, 2023. <a href="https://doi.org/10.15479/AT:ISTA:12370">https://doi.org/10.15479/AT:ISTA:12370</a>.'
  ieee: 'D. Gupta, A. L. Sumser, and M. A. Jösch, “Research Data for: Panoramic visual
    statistics shape retina-wide organization of receptive fields.” Institute of Science
    and Technology Austria, 2023.'
  ista: 'Gupta D, Sumser AL, Jösch MA. 2023. Research Data for: Panoramic visual statistics
    shape retina-wide organization of receptive fields, Institute of Science and Technology
    Austria, <a href="https://doi.org/10.15479/AT:ISTA:12370">10.15479/AT:ISTA:12370</a>.'
  mla: 'Gupta, Divyansh, et al. <i>Research Data for: Panoramic Visual Statistics
    Shape Retina-Wide Organization of Receptive Fields</i>. Institute of Science and
    Technology Austria, 2023, doi:<a href="https://doi.org/10.15479/AT:ISTA:12370">10.15479/AT:ISTA:12370</a>.'
  short: D. Gupta, A.L. Sumser, M.A. Jösch, (2023).
contributor:
- contributor_type: researcher
  first_name: Olga
  id: 3C0C7BC6-F248-11E8-B48F-1D18A9856A87
  last_name: Symonova
- contributor_type: researcher
  first_name: Wiktor F
  id: 358A453A-F248-11E8-B48F-1D18A9856A87
  last_name: Mlynarski
- contributor_type: researcher
  first_name: Jan
  id: f7f724c3-9d6f-11ed-9f44-e5c5f3a5bee2
  last_name: Svaton
date_created: 2023-01-25T12:45:18Z
date_published: 2023-01-26T00:00:00Z
date_updated: 2023-10-04T11:41:04Z
day: '26'
ddc:
- '571'
department:
- _id: GradSch
- _id: MaJö
doi: 10.15479/AT:ISTA:12370
ec_funded: 1
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month: '01'
oa: 1
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project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 626c45b5-2b32-11ec-9570-e509828c1ba6
  grant_number: P34015
  name: Efficient coding with biophysical realism
- _id: 2634E9D2-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '756502'
  name: Circuits of Visual Attention
- _id: 266D407A-B435-11E9-9278-68D0E5697425
  grant_number: LT000256
  name: Neuronal networks of salience and spatial detection in the murine superior
    colliculus
- _id: 264FEA02-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 1098-2017
  name: Connecting sensory with motor processing in the superior colliculus
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '12349'
    relation: used_in_publication
    status: public
status: public
title: 'Research Data for: Panoramic visual statistics shape retina-wide organization
  of receptive fields'
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: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2023'
...
---
_id: '12470'
abstract:
- lang: eng
  text: "The brain is an exceptionally sophisticated organ consisting of billions
    of cells and trillions of \r\nconnections that orchestrate our cognition and behavior.
    To decode its complex connectivity, it is \r\npivotal to disentangle its intricate
    architecture spanning from cm-sized circuits down to tens of \r\nnm-small synapses.\r\nTo
    achieve this goal, I developed CATS – Comprehensive Analysis of nervous Tissue
    across \r\nScales, a versatile toolbox for obtaining a holistic view of nervous
    tissue context with (super\x02resolution) fluorescence microscopy. CATS combines
    comprehensive labeling of the extracellular\r\nspace, that is compatible with
    chemical fixation, with information on molecular markers, super\x02resolved data
    acquisition and machine-learning based data analysis for segmentation and synapse
    \r\nidentification.\r\nI used CATS to analyze key features of nervous tissue connectivity,
    ranging from whole tissue \r\narchitecture, neuronal in- and output-fields, down
    to synapse morphology.\r\nFocusing on the hippocampal circuitry, I quantified
    synaptic transmission properties of mossy \r\nfiber boutons and analyzed the connectivity
    pattern of dentate gyrus granule cells with CA3 \r\npyramidal neurons. This shows
    that CATS is a viable tool to study hallmarks of neuronal \r\nconnectivity with
    light microscopy."
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
- _id: EM-Fac
- _id: M-Shop
- _id: ScienComp
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Julia M
  full_name: Michalska, Julia M
  id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
  last_name: Michalska
  orcid: 0000-0003-3862-1235
citation:
  ama: Michalska JM. A versatile toolbox for the comprehensive analysis of nervous
    tissue organization with light microscopy. 2023. doi:<a href="https://doi.org/10.15479/at:ista:12470">10.15479/at:ista:12470</a>
  apa: Michalska, J. M. (2023). <i>A versatile toolbox for the comprehensive analysis
    of nervous tissue organization with light microscopy</i>. Institute of Science
    and Technology Austria. <a href="https://doi.org/10.15479/at:ista:12470">https://doi.org/10.15479/at:ista:12470</a>
  chicago: Michalska, Julia M. “A Versatile Toolbox for the Comprehensive Analysis
    of Nervous Tissue Organization with Light Microscopy.” Institute of Science and
    Technology Austria, 2023. <a href="https://doi.org/10.15479/at:ista:12470">https://doi.org/10.15479/at:ista:12470</a>.
  ieee: J. M. Michalska, “A versatile toolbox for the comprehensive analysis of nervous
    tissue organization with light microscopy,” Institute of Science and Technology
    Austria, 2023.
  ista: Michalska JM. 2023. A versatile toolbox for the comprehensive analysis of
    nervous tissue organization with light microscopy. Institute of Science and Technology
    Austria.
  mla: Michalska, Julia M. <i>A Versatile Toolbox for the Comprehensive Analysis of
    Nervous Tissue Organization with Light Microscopy</i>. Institute of Science and
    Technology Austria, 2023, doi:<a href="https://doi.org/10.15479/at:ista:12470">10.15479/at:ista:12470</a>.
  short: J.M. Michalska, A Versatile Toolbox for the Comprehensive Analysis of Nervous
    Tissue Organization with Light Microscopy, Institute of Science and Technology
    Austria, 2023.
date_created: 2023-01-31T15:10:53Z
date_published: 2023-01-09T00:00:00Z
date_updated: 2023-08-31T12:26:58Z
day: '09'
ddc:
- '610'
degree_awarded: PhD
department:
- _id: GradSch
- _id: JoDa
doi: 10.15479/at:ista:12470
ec_funded: 1
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  date_updated: 2023-07-27T22:30:54Z
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file_date_updated: 2023-07-27T22:30:54Z
has_accepted_license: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: '201'
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 26AA4EF2-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232-B24
  name: Molecular Drug Targets
publication_identifier:
  isbn:
  - ' 978-3-99078-026-8'
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '11943'
    relation: part_of_dissertation
    status: public
  - id: '11950'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
title: A versatile toolbox for the comprehensive analysis of nervous tissue organization
  with light microscopy
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: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2023'
...
---
_id: '12716'
abstract:
- lang: eng
  text: "The process of detecting and evaluating sensory information to guide behaviour
    is termed perceptual decision-making (PDM), and is critical for the ability of
    an organism to interact with its external world. Individuals with autism, a neurodevelopmental
    condition primarily characterised by social and communication difficulties, frequently
    exhibit altered sensory processing and PDM difficulties are widely reported. Recent
    technological advancements have pushed forward our understanding of the genetic
    changes accompanying this condition, however our understanding of how these mutations
    affect the function of specific neuronal circuits and bring about the corresponding
    behavioural changes remains limited. Here, we use an innate PDM task, the looming
    avoidance response (LAR) paradigm, to identify a convergent behavioural abnormality
    across three molecularly distinct genetic mouse models of autism (Cul3, Setd5
    and Ptchd1). Although mutant mice can rapidly detect threatening visual stimuli,
    their responses are consistently delayed, requiring longer to initiate an appropriate
    response than their wild-type siblings. Mutant animals show abnormal adaptation
    in both their stimulus- evoked escape responses and exploratory dynamics following
    repeated stimulus presentations. Similarly delayed behavioural responses are observed
    in wild-type animals when faced with more ambiguous threats, suggesting the mutant
    phenotype could arise from a dysfunction in the flexible control of this PDM process.\r\nOur
    knowledge of the core neuronal circuitry mediating the LAR facilitated a detailed
    dissection of the neuronal mechanisms underlying the behavioural impairment. In
    vivo extracellular recording revealed that visual responses were unaffected within
    a key brain region for the rapid processing of visual threats, the superior colliculus
    (SC), indicating that the behavioural delay was unlikely to originate from sensory
    impairments. Delayed behavioural responses were recapitulated in the Setd5 model
    following optogenetic stimulation of the excitatory output neurons of the SC,
    which are known to mediate escape initiation through the activation of cells in
    the underlying dorsal periaqueductal grey (dPAG). In vitro patch-clamp recordings
    of dPAG cells uncovered a stark hypoexcitability phenotype in two out of the three
    genetic models investigated (Setd5 and Ptchd1), that in Setd5, is mediated by
    the misregulation of voltage-gated potassium channels. Overall, our results show
    that the ability to use visual information to drive efficient escape responses
    is impaired in three diverse genetic mouse models of autism and that, in one of
    the models studied, this behavioural delay likely originates from differences
    in the intrinsic excitability of a key subcortical node, the dPAG. Furthermore,
    this work showcases the use of an innate behavioural paradigm to mechanistically
    dissect PDM processes in autism."
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: LifeSc
- _id: M-Shop
- _id: CampIT
alternative_title:
- ISTA Thesis
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
citation:
  ama: Burnett L. To flee, or not to flee? Using innate defensive behaviours to investigate
    rapid perceptual decision-making through subcortical circuits in mouse models
    of autism. 2023. doi:<a href="https://doi.org/10.15479/at:ista:12716">10.15479/at:ista:12716</a>
  apa: Burnett, L. (2023). <i>To flee, or not to flee? Using innate defensive behaviours
    to investigate rapid perceptual decision-making through subcortical circuits in
    mouse models of autism</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:12716">https://doi.org/10.15479/at:ista:12716</a>
  chicago: Burnett, Laura. “To Flee, or Not to Flee? Using Innate Defensive Behaviours
    to Investigate Rapid Perceptual Decision-Making through Subcortical Circuits in
    Mouse Models of Autism.” Institute of Science and Technology Austria, 2023. <a
    href="https://doi.org/10.15479/at:ista:12716">https://doi.org/10.15479/at:ista:12716</a>.
  ieee: L. Burnett, “To flee, or not to flee? Using innate defensive behaviours to
    investigate rapid perceptual decision-making through subcortical circuits in mouse
    models of autism,” Institute of Science and Technology Austria, 2023.
  ista: Burnett L. 2023. To flee, or not to flee? Using innate defensive behaviours
    to investigate rapid perceptual decision-making through subcortical circuits in
    mouse models of autism. Institute of Science and Technology Austria.
  mla: Burnett, Laura. <i>To Flee, or Not to Flee? Using Innate Defensive Behaviours
    to Investigate Rapid Perceptual Decision-Making through Subcortical Circuits in
    Mouse Models of Autism</i>. Institute of Science and Technology Austria, 2023,
    doi:<a href="https://doi.org/10.15479/at:ista:12716">10.15479/at:ista:12716</a>.
  short: L. Burnett, To Flee, or Not to Flee? Using Innate Defensive Behaviours to
    Investigate Rapid Perceptual Decision-Making through Subcortical Circuits in Mouse
    Models of Autism, Institute of Science and Technology Austria, 2023.
date_created: 2023-03-08T15:19:45Z
date_published: 2023-03-10T00:00:00Z
date_updated: 2023-04-05T10:59:04Z
day: '10'
ddc:
- '599'
- '573'
degree_awarded: PhD
department:
- _id: GradSch
- _id: MaJö
doi: 10.15479/at:ista:12716
ec_funded: 1
file:
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  checksum: 6c6d9cc2c4cdacb74e6b1047a34d7332
  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
  creator: lburnett
  date_created: 2023-03-08T15:08:46Z
  date_updated: 2023-03-08T15:08:46Z
  file_id: '12717'
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  checksum: cebc77705288bf4382db9b3541483cd0
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  creator: lburnett
  date_created: 2023-03-08T15:08:46Z
  date_updated: 2023-03-08T15:08:46Z
  file_id: '12718'
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  success: 1
file_date_updated: 2023-03-08T15:08:46Z
has_accepted_license: '1'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: '178'
project:
- _id: 2634E9D2-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '756502'
  name: Circuits of Visual Attention
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Maximilian A
  full_name: Jösch, Maximilian A
  id: 2BD278E6-F248-11E8-B48F-1D18A9856A87
  last_name: Jösch
  orcid: 0000-0002-3937-1330
title: To flee, or not to flee? Using innate defensive behaviours to investigate rapid
  perceptual decision-making through subcortical circuits in mouse models of autism
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2023'
...
---
_id: '12802'
abstract:
- lang: eng
  text: Little is known about the critical metabolic changes that neural cells have
    to undergo during development and how temporary shifts in this program can influence
    brain circuitries and behavior. Inspired by the discovery that mutations in SLC7A5,
    a transporter of metabolically essential large neutral amino acids (LNAAs), lead
    to autism, we employed metabolomic profiling to study the metabolic states of
    the cerebral cortex across different developmental stages. We found that the forebrain
    undergoes significant metabolic remodeling throughout development, with certain
    groups of metabolites showing stage-specific changes, but what are the consequences
    of perturbing this metabolic program? By manipulating Slc7a5 expression in neural
    cells, we found that the metabolism of LNAAs and lipids are interconnected in
    the cortex. Deletion of Slc7a5 in neurons affects the postnatal metabolic state,
    leading to a shift in lipid metabolism. Additionally, it causes stage- and cell-type-specific
    alterations in neuronal activity patterns, resulting in a long-term circuit dysfunction.
acknowledged_ssus:
- _id: PreCl
- _id: EM-Fac
- _id: Bio
- _id: LifeSc
acknowledgement: We thank A. Freeman and V. Voronin for technical assistance, S. Deixler,
  A. Stichelberger, M. Schunn, and the Preclinical Facility for managing our animal
  colony. We thank L. Andersen and J. Sonntag, who were involved in generating the
  MADM lines. We thank the ISTA LSF Mass Spectrometry Core Facility for assistance
  with the proteomic analysis, as well as the ISTA electron microscopy and Imaging
  and Optics facility for technical support. Metabolomics LC-MS/MS analysis was performed
  by the Metabolomics Facility at Vienna BioCenter Core Facilities (VBCF). We acknowledge
  the support of the EMBL Metabolomics Core Facility (MCF) for lipidomics and intracellular
  metabolomics mass spectrometry data acquisition and analysis. RNA sequencing was
  performed by the Next Generation Sequencing Facility at VBCF. Schematics were generated
  using Biorender.com. This work was supported by the Austrian Science Fund (FWF,
  DK W1232-B24) and by the European Union’s Horizon 2020 research and innovation program
  (ERC) grant 725780 (LinPro) to S.H. and 715508 (REVERSEAUTISM) to G.N.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Lisa
  full_name: Knaus, Lisa
  id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
  last_name: Knaus
- first_name: Bernadette
  full_name: Basilico, Bernadette
  id: 36035796-5ACA-11E9-A75E-7AF2E5697425
  last_name: Basilico
  orcid: 0000-0003-1843-3173
- first_name: Daniel
  full_name: Malzl, Daniel
  last_name: Malzl
- first_name: Maria
  full_name: Gerykova Bujalkova, Maria
  last_name: Gerykova Bujalkova
- first_name: Mateja
  full_name: Smogavec, Mateja
  last_name: Smogavec
- first_name: Lena A.
  full_name: Schwarz, Lena A.
  last_name: Schwarz
- first_name: Sarah
  full_name: Gorkiewicz, Sarah
  id: f141a35d-15a9-11ec-9fb2-fef6becc7b6f
  last_name: Gorkiewicz
- first_name: Nicole
  full_name: Amberg, Nicole
  id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
  last_name: Amberg
  orcid: 0000-0002-3183-8207
- first_name: Florian
  full_name: Pauler, Florian
  id: 48EA0138-F248-11E8-B48F-1D18A9856A87
  last_name: Pauler
  orcid: 0000-0002-7462-0048
- first_name: Christian
  full_name: Knittl-Frank, Christian
  last_name: Knittl-Frank
- first_name: Marianna
  full_name: Tassinari, Marianna
  id: 7af593f1-d44a-11ed-bf94-a3646a6bb35e
  last_name: Tassinari
- first_name: Nuno
  full_name: Maulide, Nuno
  last_name: Maulide
- first_name: Thomas
  full_name: Rülicke, Thomas
  last_name: Rülicke
- first_name: Jörg
  full_name: Menche, Jörg
  last_name: Menche
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
citation:
  ama: Knaus L, Basilico B, Malzl D, et al. Large neutral amino acid levels tune perinatal
    neuronal excitability and survival. <i>Cell</i>. 2023;186(9):1950-1967.e25. doi:<a
    href="https://doi.org/10.1016/j.cell.2023.02.037">10.1016/j.cell.2023.02.037</a>
  apa: Knaus, L., Basilico, B., Malzl, D., Gerykova Bujalkova, M., Smogavec, M., Schwarz,
    L. A., … Novarino, G. (2023). Large neutral amino acid levels tune perinatal neuronal
    excitability and survival. <i>Cell</i>. Elsevier. <a href="https://doi.org/10.1016/j.cell.2023.02.037">https://doi.org/10.1016/j.cell.2023.02.037</a>
  chicago: Knaus, Lisa, Bernadette Basilico, Daniel Malzl, Maria Gerykova Bujalkova,
    Mateja Smogavec, Lena A. Schwarz, Sarah Gorkiewicz, et al. “Large Neutral Amino
    Acid Levels Tune Perinatal Neuronal Excitability and Survival.” <i>Cell</i>. Elsevier,
    2023. <a href="https://doi.org/10.1016/j.cell.2023.02.037">https://doi.org/10.1016/j.cell.2023.02.037</a>.
  ieee: L. Knaus <i>et al.</i>, “Large neutral amino acid levels tune perinatal neuronal
    excitability and survival,” <i>Cell</i>, vol. 186, no. 9. Elsevier, p. 1950–1967.e25,
    2023.
  ista: Knaus L, Basilico B, Malzl D, Gerykova Bujalkova M, Smogavec M, Schwarz LA,
    Gorkiewicz S, Amberg N, Pauler F, Knittl-Frank C, Tassinari M, Maulide N, Rülicke
    T, Menche J, Hippenmeyer S, Novarino G. 2023. Large neutral amino acid levels
    tune perinatal neuronal excitability and survival. Cell. 186(9), 1950–1967.e25.
  mla: Knaus, Lisa, et al. “Large Neutral Amino Acid Levels Tune Perinatal Neuronal
    Excitability and Survival.” <i>Cell</i>, vol. 186, no. 9, Elsevier, 2023, p. 1950–1967.e25,
    doi:<a href="https://doi.org/10.1016/j.cell.2023.02.037">10.1016/j.cell.2023.02.037</a>.
  short: L. Knaus, B. Basilico, D. Malzl, M. Gerykova Bujalkova, M. Smogavec, L.A.
    Schwarz, S. Gorkiewicz, N. Amberg, F. Pauler, C. Knittl-Frank, M. Tassinari, N.
    Maulide, T. Rülicke, J. Menche, S. Hippenmeyer, G. Novarino, Cell 186 (2023) 1950–1967.e25.
date_created: 2023-04-05T08:15:40Z
date_published: 2023-04-27T00:00:00Z
date_updated: 2024-02-07T08:03:32Z
day: '27'
ddc:
- '570'
department:
- _id: SiHi
- _id: GaNo
doi: 10.1016/j.cell.2023.02.037
ec_funded: 1
external_id:
  isi:
  - '000991468700001'
file:
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  checksum: 47e94fbe19e86505b429cb7a5b503ce6
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  creator: dernst
  date_created: 2023-05-02T09:26:21Z
  date_updated: 2023-05-02T09:26:21Z
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  file_size: 15712841
  relation: main_file
  success: 1
file_date_updated: 2023-05-02T09:26:21Z
has_accepted_license: '1'
intvolume: '       186'
isi: 1
issue: '9'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: 1950-1967.e25
project:
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232-B24
  name: Molecular Drug Targets
- _id: 260018B0-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '725780'
  name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 25444568-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715508'
  name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
    and in vitro Models
publication: Cell
publication_identifier:
  issn:
  - 0092-8674
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/feed-them-or-lose-them/
  record:
  - id: '13107'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Large neutral amino acid levels tune perinatal neuronal excitability and survival
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: 186
year: '2023'
...
---
_id: '12809'
abstract:
- lang: eng
  text: "Understanding the mechanisms of learning and memory formation has always
    been one of\r\nthe main goals in neuroscience. Already Pavlov (1927) in his early
    days has used his classic\r\nconditioning experiments to study the neural mechanisms
    governing behavioral adaptation.\r\nWhat was not known back then was that the
    part of the brain that is largely responsible for\r\nthis type of associative
    learning is the cerebellum.\r\nSince then, plenty of theories on cerebellar learning
    have emerged. Despite their differences,\r\none thing they all have in common
    is that learning relies on synaptic and intrinsic plasticity.\r\nThe goal of my
    PhD project was to unravel the molecular mechanisms underlying synaptic\r\nplasticity
    in two synapses that have been shown to be implicated in motor learning, in an\r\neffort
    to understand how learning and memory formation are processed in the cerebellum.\r\nOne
    of the earliest and most well-known cerebellar theories postulates that motor
    learning\r\nlargely depends on long-term depression at the parallel fiber-Purkinje
    cell (PC-PC) synapse.\r\nHowever, the discovery of other types of plasticity in
    the cerebellar circuitry, like long-term\r\npotentiation (LTP) at the PC-PC synapse,
    potentiation of molecular layer interneurons (MLIs),\r\nand plasticity transfer
    from the cortex to the cerebellar/ vestibular nuclei has increased the\r\npopularity
    of the idea that multiple sites of plasticity might be involved in learning.\r\nStill
    a lot remains unknown about the molecular mechanisms responsible for these types
    of\r\nplasticity and whether they occur during physiological learning.\r\nIn the
    first part of this thesis we have analyzed the variation and nanodistribution
    of voltagegated calcium channels (VGCCs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
    acid\r\ntype glutamate receptors (AMPARs) on the parallel fiber-Purkinje cell
    synapse after vestibuloocular reflex phase reversal adaptation, a behavior that
    has been suggested to rely on PF-PC\r\nLTP. We have found that on the last day
    of adaptation there is no learning trace in form of\r\nVGCCs nor AMPARs variation
    at the PF-PC synapse, but instead a decrease in the number of\r\nPF-PC synapses.
    These data seem to support the view that learning is only stored in the\r\ncerebellar
    cortex in an initial learning phase, being transferred later to the vestibular
    nuclei.\r\nNext, we have studied the role of MLIs in motor learning using a relatively
    simple and well characterized behavioral paradigm – horizontal optokinetic reflex
    (HOKR) adaptation. We\r\nhave found behavior-induced MLI potentiation in form
    of release probability increase that\r\ncould be explained by the increase of
    VGCCs at the presynaptic side. Our results strengthen\r\nthe idea of distributed
    cerebellar plasticity contributing to learning and provide a novel\r\nmechanism
    for release probability increase. "
acknowledged_ssus:
- _id: EM-Fac
- _id: Bio
- _id: PreCl
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Catarina
  full_name: Alcarva, Catarina
  id: 3A96634C-F248-11E8-B48F-1D18A9856A87
  last_name: Alcarva
citation:
  ama: 'Alcarva C. Plasticity in the cerebellum: What molecular mechanisms are behind
    physiological learning. 2023. doi:<a href="https://doi.org/10.15479/at:ista:12809">10.15479/at:ista:12809</a>'
  apa: 'Alcarva, C. (2023). <i>Plasticity in the cerebellum: What molecular mechanisms
    are behind physiological learning</i>. Institute of Science and Technology Austria.
    <a href="https://doi.org/10.15479/at:ista:12809">https://doi.org/10.15479/at:ista:12809</a>'
  chicago: 'Alcarva, Catarina. “Plasticity in the Cerebellum: What Molecular Mechanisms
    Are behind Physiological Learning.” Institute of Science and Technology Austria,
    2023. <a href="https://doi.org/10.15479/at:ista:12809">https://doi.org/10.15479/at:ista:12809</a>.'
  ieee: 'C. Alcarva, “Plasticity in the cerebellum: What molecular mechanisms are
    behind physiological learning,” Institute of Science and Technology Austria, 2023.'
  ista: 'Alcarva C. 2023. Plasticity in the cerebellum: What molecular mechanisms
    are behind physiological learning. Institute of Science and Technology Austria.'
  mla: 'Alcarva, Catarina. <i>Plasticity in the Cerebellum: What Molecular Mechanisms
    Are behind Physiological Learning</i>. Institute of Science and Technology Austria,
    2023, doi:<a href="https://doi.org/10.15479/at:ista:12809">10.15479/at:ista:12809</a>.'
  short: 'C. Alcarva, Plasticity in the Cerebellum: What Molecular Mechanisms Are
    behind Physiological Learning, Institute of Science and Technology Austria, 2023.'
date_created: 2023-04-06T07:54:09Z
date_published: 2023-04-06T00:00:00Z
date_updated: 2023-04-26T12:16:56Z
day: '06'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: RySh
doi: 10.15479/at:ista:12809
file:
- access_level: closed
  checksum: 35b5997d2b0acb461f9d33d073da0df5
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  date_updated: 2023-04-07T06:16:06Z
  embargo: 2024-04-07
  embargo_to: open_access
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  creator: cchlebak
  date_created: 2023-04-07T06:17:11Z
  date_updated: 2023-04-07T06:17:11Z
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  creator: cchlebak
  date_created: 2023-04-07T06:18:05Z
  date_updated: 2023-04-07T06:18:05Z
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  relation: source_file
file_date_updated: 2023-04-07T06:18:05Z
has_accepted_license: '1'
language:
- iso: eng
month: '04'
oa_version: Published Version
page: '115'
project:
- _id: 267DFB90-B435-11E9-9278-68D0E5697425
  name: 'Plasticity in the cerebellum: Which molecular mechanisms are behind physiological
    learning?'
publication_identifier:
  issn:
  - 2663 - 337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
title: 'Plasticity in the cerebellum: What molecular mechanisms are behind physiological
  learning'
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2023'
...
---
_id: '12817'
abstract:
- lang: eng
  text: 3D-reconstruction of living brain tissue down to individual synapse level
    would create opportunities for decoding the dynamics and structure-function relationships
    of the brain’s complex and dense information processing network. However, it has
    been hindered by insufficient 3D-resolution, inadequate signal-to-noise-ratio,
    and prohibitive light burden in optical imaging, whereas electron microscopy is
    inherently static. Here we solved these challenges by developing an integrated
    optical/machine learning technology, LIONESS (Live Information-Optimized Nanoscopy
    Enabling Saturated Segmentation). It leverages optical modifications to stimulated
    emission depletion (STED) microscopy in comprehensively, extracellularly labelled
    tissue and prior information on sample structure via machine learning to simultaneously
    achieve isotropic super-resolution, high signal-to-noise-ratio, and compatibility
    with living tissue. This allows dense deep-learning-based instance segmentation
    and 3D-reconstruction at synapse level incorporating molecular, activity, and
    morphodynamic information. LIONESS opens up avenues for studying the dynamic functional
    (nano-)architecture of living brain tissue.
acknowledged_ssus:
- _id: ScienComp
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
- _id: E-Lib
acknowledgement: 'We thank J. Vorlaufer, N. Agudelo, A. Wartak for microscope maintenance
  and troubleshooting, C. Kreuzinger and A. Freeman for technical assistance, and
  M. Šuplata for hardware control support, and Márcia Cunha dos Santos for initial
  exploration of software. We thank Paul Henderson for advice on deep-learning training
  and Michael Sixt, Scott Boyd, and Tamara Weiss for discussions and critical reading
  of the manuscript. Luke Lavis (Janelia Research Campus) generously provided JF585-HaloTag
  ligand. '
article_processing_charge: No
author:
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
citation:
  ama: Danzl JG. Research data for the publication “Dense 4D nanoscale reconstruction
    of living brain tissue.” 2023. doi:<a href="https://doi.org/10.15479/AT:ISTA:12817">10.15479/AT:ISTA:12817</a>
  apa: Danzl, J. G. (2023). Research data for the publication “Dense 4D nanoscale
    reconstruction of living brain tissue.” Institute of Science and Technology Austria.
    <a href="https://doi.org/10.15479/AT:ISTA:12817">https://doi.org/10.15479/AT:ISTA:12817</a>
  chicago: Danzl, Johann G. “Research Data for the Publication ‘Dense 4D Nanoscale
    Reconstruction of Living Brain Tissue.’” Institute of Science and Technology Austria,
    2023. <a href="https://doi.org/10.15479/AT:ISTA:12817">https://doi.org/10.15479/AT:ISTA:12817</a>.
  ieee: J. G. Danzl, “Research data for the publication ‘Dense 4D nanoscale reconstruction
    of living brain tissue.’” Institute of Science and Technology Austria, 2023.
  ista: Danzl JG. 2023. Research data for the publication ‘Dense 4D nanoscale reconstruction
    of living brain tissue’, Institute of Science and Technology Austria, <a href="https://doi.org/10.15479/AT:ISTA:12817">10.15479/AT:ISTA:12817</a>.
  mla: Danzl, Johann G. <i>Research Data for the Publication “Dense 4D Nanoscale Reconstruction
    of Living Brain Tissue.”</i> Institute of Science and Technology Austria, 2023,
    doi:<a href="https://doi.org/10.15479/AT:ISTA:12817">10.15479/AT:ISTA:12817</a>.
  short: J.G. Danzl, (2023).
contributor:
- first_name: Philipp
  id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
  last_name: Velicky
  orcid: 0000-0002-2340-7431
- first_name: Eder
  id: 3FB91342-F248-11E8-B48F-1D18A9856A87
  last_name: Miguel Villalba
- first_name: Julia M
  id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
  last_name: Michalska
- first_name: Julia
  id: 46E28B80-F248-11E8-B48F-1D18A9856A87
  last_name: Lyudchik
- first_name: Donglai
  last_name: Wei
- first_name: Zudi
  last_name: Lin
- first_name: Jake
  id: 63836096-4690-11EA-BD4E-32803DDC885E
  last_name: Watson
  orcid: 0000-0002-8698-3823
- first_name: Jakob
  last_name: Troidl
- first_name: Johanna
  last_name: Beyer
- first_name: Yoav
  id: 43DF3136-F248-11E8-B48F-1D18A9856A87
  last_name: Ben Simon
- first_name: Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Wiebke
  id: 425C1CE8-F248-11E8-B48F-1D18A9856A87
  last_name: Jahr
- first_name: Alban
  id: 9ac8f577-2357-11eb-997a-e566c5550886
  last_name: Cenameri
- first_name: Johannes
  last_name: Broichhagen
- first_name: 'Seth G. N. '
  last_name: Grant
- first_name: Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
- first_name: Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Hanspeter
  last_name: Pfister
- first_name: Bernd
  id: 49876194-F248-11E8-B48F-1D18A9856A87
  last_name: Bickel
  orcid: 0000-0001-6511-9385
date_created: 2023-04-07T11:37:40Z
date_published: 2023-05-19T00:00:00Z
date_updated: 2024-01-10T08:37:48Z
day: '19'
ddc:
- '570'
department:
- _id: JoDa
doi: 10.15479/AT:ISTA:12817
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