---
OA_place: repository
_id: '18688'
abstract:
- lang: eng
text: The human brain has remarkable computational power. It generates sophisticated
behavioral sequences, stores engrams over an individual’s lifetime, and produces
higher cognitive functions up to the level of consciousness. However, so little
of our neuroscience knowledge covers the human brain, and it remains unknown whether
this organ is truly unique, or is a scaled version of the extensively studied
rodent brain. To address this fundamental question, we determined the cellular,
synaptic, and connectivity rules of the hippocampal CA3 recurrent circuit using
multicellular patch clamp-recording. This circuit is the largest autoassociative
network in the brain, and plays a key role in memory and higher-order computations
such as pattern separation and pattern completion. We demonstrate that human hippocampal
CA3 employs sparse connectivity, in stark contrast to neocortical recurrent networks.
Connectivity sparsifies from rodents to humans, providing a circuit architecture
that maximizes associational power. Unitary synaptic events at human CA3–CA3 synapses
showed both distinct species-specific and circuit-dependent properties, with high
reliability, unique amplitude precision, and long integration times. We also identify
differential scaling rules between hippocampal pathways from rodents to humans,
with a moderate increase in the convergence of CA3 inputs per cell, but a marked
increase in human mossy fiber innervation. Anatomically guided full-scale modeling
suggests that the human brain’s sparse connectivity, expanded neuronal number,
and reliable synaptic signaling combine to enhance the associative memory storage
capacity of CA3. Together, our results reveal unique rules of connectivity and
synaptic signaling in the human hippocampus, demonstrating the absolute necessity
of human brain research and beginning to unravel the remarkable performance of
our autoassociative memory circuits.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: M-Shop
- _id: PreCl
- _id: ScienComp
acknowledgement: We thank Florian Marr for excellent technical assistance, Christina
Altmutter and Julia Flor for technical support, Alois Schlögl for programming, Todor
Asenov for development of the transportation box for human brain tissue, Tim Vogels
for guidance on simulations, Marcus Huber for mathematical advice, and Eleftheria
Kralli-Beller for manuscript editing. This research was supported by the Scientific
Services Units (SSUs) of ISTA, and we are particularly grateful for assistance from
Christoph Sommer and the Imaging and Optics Facility, Preclinical Facility, Life
Science Facility, Miba Machine Shop, and Scientific Computing. We also acknowledge
the excellent support of the Medical University of Vienna Department of Neurosurgery
staff, Romana Hoeftberger and the Division of Neuropathology and Neurochemistry,
and Gregor Kasprian and the Division of Neuroradiology and Musculoskeletal Radiology.
The project received funding from the European Research Council (ERC) under the
European Union’s Horizon 2020 research and innovation programme (Marie Skłodowska-Curie
Actions Individual Fellowship no. 101026635 to J.F.W.), the Austrian Science Fund
(FWF; grant PAT 4178023 to P.J.; grant DK W1232 to M.R.T. and J.G.D.) and the Austrian
Academy of Sciences (DOC fellowship 26137 to M.R.T.).
article_processing_charge: No
author:
- first_name: Jake F.
full_name: Watson, Jake F.
last_name: Watson
- first_name: Victor
full_name: Vargas-Barroso, Victor
last_name: Vargas-Barroso
- first_name: Rebecca J.
full_name: Morse-Mora, Rebecca J.
last_name: Morse-Mora
- first_name: Andrea
full_name: Navas-Olive, Andrea
last_name: Navas-Olive
- first_name: Mojtaba
full_name: Tavakoli, Mojtaba
id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
last_name: Tavakoli
orcid: 0000-0002-7667-6854
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
- first_name: Matthias
full_name: Tomschik, Matthias
last_name: Tomschik
- first_name: Karl
full_name: Rössler, Karl
last_name: Rössler
- 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: Watson JF, Vargas-Barroso V, Morse-Mora RJ, et al. Human hippocampal CA3 uses
specific functional connectivity rules for efficient associative memory. bioRxiv.
doi:10.1101/2024.05.02.592169
apa: Watson, J. F., Vargas-Barroso, V., Morse-Mora, R. J., Navas-Olive, A., Tavakoli,
M., Danzl, J. G., … Jonas, P. M. (n.d.). Human hippocampal CA3 uses specific functional
connectivity rules for efficient associative memory. bioRxiv. https://doi.org/10.1101/2024.05.02.592169
chicago: Watson, Jake F., Victor Vargas-Barroso, Rebecca J. Morse-Mora, Andrea Navas-Olive,
Mojtaba Tavakoli, Johann G Danzl, Matthias Tomschik, Karl Rössler, and Peter M
Jonas. “Human Hippocampal CA3 Uses Specific Functional Connectivity Rules for
Efficient Associative Memory.” BioRxiv, n.d. https://doi.org/10.1101/2024.05.02.592169.
ieee: J. F. Watson et al., “Human hippocampal CA3 uses specific functional
connectivity rules for efficient associative memory,” bioRxiv. .
ista: Watson JF, Vargas-Barroso V, Morse-Mora RJ, Navas-Olive A, Tavakoli M, Danzl
JG, Tomschik M, Rössler K, Jonas PM. Human hippocampal CA3 uses specific functional
connectivity rules for efficient associative memory. bioRxiv, 10.1101/2024.05.02.592169.
mla: Watson, Jake F., et al. “Human Hippocampal CA3 Uses Specific Functional Connectivity
Rules for Efficient Associative Memory.” BioRxiv, doi:10.1101/2024.05.02.592169.
short: J.F. Watson, V. Vargas-Barroso, R.J. Morse-Mora, A. Navas-Olive, M. Tavakoli,
J.G. Danzl, M. Tomschik, K. Rössler, P.M. Jonas, BioRxiv (n.d.).
corr_author: '1'
date_created: 2024-12-19T11:35:08Z
date_published: 2024-05-02T00:00:00Z
date_updated: 2026-07-28T08:33:51Z
day: '02'
department:
- _id: JoDa
- _id: PeJo
doi: 10.1101/2024.05.02.592169
ec_funded: 1
fulldoi: https://doi.org/10.1101/2024.05.02.592169
language:
- iso: eng
main_file_link:
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url: https://doi.org/10.1101/2024.05.02.592169
month: '05'
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oa_version: Preprint
project:
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
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call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 6285a163-2b32-11ec-9570-8e204ca2dba5
grant_number: '26137'
name: Studying Organelle Structure and Function at Nanoscale Resolution with Expansion
Microscopy
publication: bioRxiv
publication_status: draft
related_material:
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relation: dissertation_contains
status: public
status: public
title: Human hippocampal CA3 uses specific functional connectivity rules for efficient
associative memory
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2024'
...
---
OA_embargo: '20'
OA_place: publisher
_id: '18681'
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: LifeSc
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Mojtaba
full_name: Tavakoli, Mojtaba
id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
last_name: Tavakoli
orcid: 0000-0002-7667-6854
citation:
ama: 'Tavakoli M. Developing molecular and structural tools for studying brain architecture
with super resolution expansion microscopy. LICONN: Molecularly-informed connectomics
reconstruction with light microscopy. 2024. doi:10.15479/at:ista:18681'
apa: 'Tavakoli, M. (2024). Developing molecular and structural tools for studying
brain architecture with super resolution expansion microscopy. LICONN: Molecularly-informed
connectomics reconstruction with light microscopy. Institute of Science and
Technology Austria. https://doi.org/10.15479/at:ista:18681'
chicago: 'Tavakoli, Mojtaba. “Developing Molecular and Structural Tools for Studying
Brain Architecture with Super Resolution Expansion Microscopy. LICONN: Molecularly-Informed
Connectomics Reconstruction with Light Microscopy.” Institute of Science and Technology
Austria, 2024. https://doi.org/10.15479/at:ista:18681.'
ieee: 'M. Tavakoli, “Developing molecular and structural tools for studying brain
architecture with super resolution expansion microscopy. LICONN: Molecularly-informed
connectomics reconstruction with light microscopy,” Institute of Science and Technology
Austria, 2024.'
ista: 'Tavakoli M. 2024. Developing molecular and structural tools for studying
brain architecture with super resolution expansion microscopy. LICONN: Molecularly-informed
connectomics reconstruction with light microscopy. Institute of Science and Technology
Austria.'
mla: 'Tavakoli, Mojtaba. Developing Molecular and Structural Tools for Studying
Brain Architecture with Super Resolution Expansion Microscopy. LICONN: Molecularly-Informed
Connectomics Reconstruction with Light Microscopy. Institute of Science and
Technology Austria, 2024, doi:10.15479/at:ista:18681.'
short: 'M. Tavakoli, Developing Molecular and Structural Tools for Studying Brain
Architecture with Super Resolution Expansion Microscopy. LICONN: Molecularly-Informed
Connectomics Reconstruction with Light Microscopy, Institute of Science and Technology
Austria, 2024.'
corr_author: '1'
das_tickbox: '1'
date_created: 2024-12-19T02:30:39Z
date_published: 2024-12-20T00:00:00Z
date_updated: 2026-07-28T08:33:52Z
day: '20'
ddc:
- '600'
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degree_awarded: PhD
department:
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- _id: JoDa
doi: 10.15479/at:ista:18681
doi_confirm: '1'
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license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '12'
oa_version: Published Version
page: '230'
project:
- _id: 6285a163-2b32-11ec-9570-8e204ca2dba5
grant_number: '26137'
name: Studying Organelle Structure and Function at Nanoscale Resolution with Expansion
Microscopy
- _id: 26AA4EF2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
publication_identifier:
isbn:
- 978-3-99078-048-0
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
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relation: part_of_dissertation
status: public
- id: '18688'
relation: part_of_dissertation
status: public
- id: '18677'
relation: part_of_dissertation
status: public
- id: '18689'
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: 'Developing molecular and structural tools for studying brain architecture
with super resolution expansion microscopy. LICONN: Molecularly-informed connectomics
reconstruction with light microscopy'
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: '2024'
...
---
OA_place: publisher
_id: '15352'
abstract:
- lang: eng
text: "Epilepsy affects about 50 to 65 million people globally. It summarizes a
spectrum of neurological\r\ndisorders that have in common a hyperactivity of the
neuronal network resulting in seizures. A common\r\nassumption is that an imbalance
between neuronal excitation and inhibition is a key mechanism in\r\nseizure generation
and epileptogeneisis. In at least one-third of the patients, current therapies
have\r\nproven unsuccessful in treating seizure progression. One potential reason
could be that the therapies\r\nonly focus on neurons. Recent studies suggest that
neuronal hyperactivity causes a microglial\r\nresponse, which reinstates brain
homeostasis. Additionally, interactions between microglia and neurons\r\nhave
been shown to inhibit neuronal firing and dampen seizure activity. However, the
exact relationship\r\nbetween microglia and seizure progression in epilepsy is
yet to be elucidated. A main bottleneck is that\r\nseveral studies investigate
microglia dynamics in ex vivo slice models, which can severely affect the\r\nmicroglia
dynamics due to their rapid response to environmental changes. On the other hand,
in vivo\r\nstudies focus mostly on behavior characterization of the epileptic
seizure phenotype and their long-term\r\nconsequences on microglia activity leaving
out the direct consequences of acute seizure activity on\r\nmicroglia dynamics.\r\nHere,
we perform a pilot study to combine electroencephalography (EEG) and in vivo live
imaging to\r\ndirectly monitor and correlate the onset of seizure activity with
microglia response. To induce seizures,\r\nwe take advantage of the kainic acid
(KA) model, which represents similar neuropathological and\r\nelectroencephalographic
features seen in human patients with temporal lobe epilepsy (TLE). After\r\nconfirmation
of induction of the seizure and microglia activity in the hippocampus as a focal
point, we\r\ninvestigated whether these changes also reached the primary visual
cortex (V1) as a secondary\r\ngeneralized seizure activity. Indeed, we found that
microglia changed their morphology at high doses\r\nof KA in the V1. Next, we
optimized each of the two methodological components: for the EEG recording,\r\nour
initial attempts under the microscope suffered from extensive electrical noise,
which overlaid the\r\nactual signal. Thus, we built a customized Faraday-cage
and confirmed that the signal-to-noise ratio\r\nwas sufficiently reduced to be
able to record brain oscillatory activity. For the in vivo live imaging of\r\nmicroglia,
we had to optimize the imaging parameters, so that we would be able to detect
microglial\r\nprocesses in a sufficient resolution to track their process changes.
Finally, we combined both\r\nmethodologies with the KA model. We confirmed that
KA induced seizure activity and found first\r\nindication that those correlate
with microglia volume changes.\r\nOverall, we have developed a first methodological
approach, which allows the analysis of the acute\r\neffects of seizure onset on
microglia. Future studies will have to continue to optimize the drift during\r\nimaging
recording and the post-image analysis. "
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
alternative_title:
- ISTA Master's Thesis
article_processing_charge: No
author:
- first_name: Julie Stefanie
full_name: Murmann, Julie Stefanie
id: 1d390868-f128-11eb-9611-a0ca5f7833b5
last_name: Murmann
citation:
ama: 'Murmann JS. Investigating acute microglia response to seizure activity in
vivo: Combining 2-Photon imaging and EEG recording. 2024. doi:10.15479/at:ista:15352'
apa: 'Murmann, J. S. (2024). Investigating acute microglia response to seizure
activity in vivo: Combining 2-Photon imaging and EEG recording. Institute
of Science and Technology Austria. https://doi.org/10.15479/at:ista:15352'
chicago: 'Murmann, Julie Stefanie. “Investigating Acute Microglia Response to Seizure
Activity in Vivo: Combining 2-Photon Imaging and EEG Recording.” Institute of
Science and Technology Austria, 2024. https://doi.org/10.15479/at:ista:15352.'
ieee: 'J. S. Murmann, “Investigating acute microglia response to seizure activity
in vivo: Combining 2-Photon imaging and EEG recording,” Institute of Science and
Technology Austria, 2024.'
ista: 'Murmann JS. 2024. Investigating acute microglia response to seizure activity
in vivo: Combining 2-Photon imaging and EEG recording. Institute of Science and
Technology Austria.'
mla: 'Murmann, Julie Stefanie. Investigating Acute Microglia Response to Seizure
Activity in Vivo: Combining 2-Photon Imaging and EEG Recording. Institute
of Science and Technology Austria, 2024, doi:10.15479/at:ista:15352.'
short: 'J.S. Murmann, Investigating Acute Microglia Response to Seizure Activity
in Vivo: Combining 2-Photon Imaging and EEG Recording, Institute of Science and
Technology Austria, 2024.'
corr_author: '1'
date_created: 2024-05-02T08:31:38Z
date_published: 2024-05-02T00:00:00Z
date_updated: 2026-04-07T13:05:00Z
day: '02'
ddc:
- '570'
degree_awarded: MS
department:
- _id: SaSi
- _id: GradSch
doi: 10.15479/at:ista:15352
file:
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content_type: application/pdf
creator: cchlebak
date_created: 2024-05-02T12:26:13Z
date_updated: 2025-05-02T22:30:04Z
embargo: 2025-05-02
file_id: '15354'
file_name: Murmann_Thesis_final_2024_2.pdf
file_size: 5936142
relation: main_file
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checksum: 43b632255372973a437ac87739cfd4db
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creator: cchlebak
date_created: 2024-05-02T12:37:56Z
date_updated: 2025-05-02T22:30:04Z
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file_size: 20645510
relation: source_file
file_date_updated: 2025-05-02T22:30:04Z
fulldoi: https://doi.org/10.15479/at:ista:15352
has_accepted_license: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '05'
oa: 1
oa_version: Published Version
page: '54'
publication_identifier:
issn:
- 2791-4585
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
title: 'Investigating acute microglia response to seizure activity in vivo: Combining
2-Photon imaging and EEG recording'
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: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '14843'
abstract:
- lang: eng
text: The coupling between Ca2+ channels and release sensors is a key factor defining
the signaling properties of a synapse. However, the coupling nanotopography at
many synapses remains unknown, and it is unclear how it changes during development.
To address these questions, we examined coupling at the cerebellar inhibitory
basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission
by paired recording and intracellular pipette perfusion revealed that the effects
of exogenous Ca2+ chelators decreased during development, despite constant reliance
of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica
labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic
P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked
vesicles were only clustered at later developmental stages. Modeling suggested
a developmental transformation from a more random to a more clustered coupling
nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point
configuration, optimizing speed, reliability, and energy efficiency of synaptic
transmission.
acknowledged_ssus:
- _id: EM-Fac
- _id: PreCl
- _id: M-Shop
acknowledgement: We thank Drs. David DiGregorio and Erwin Neher for critically reading
an earlier version of the manuscript, Ralf Schneggenburger for helpful discussions,
Benjamin Suter and Katharina Lichter for support with image analysis, Chris Wojtan
for advice on numerical solution of partial differential equations, Maria Reva for
help with Ripley analysis, Alois Schlögl for programming, and Akari Hagiwara and
Toshihisa Ohtsuka for anti-ELKS antibody. We are grateful to Florian Marr, Christina
Altmutter, and Vanessa Zheden for excellent technical assistance and to Eleftheria
Kralli-Beller for manuscript editing. This research was supported by the Scientific
Services Units (SSUs) of ISTA (Electron Microscopy Facility, Preclinical Facility,
and Machine Shop). The project received funding from the European Research Council
(ERC) under the European Union’s Horizon 2020 research and innovation program (grant
agreement no. 692692), the Fonds zur Förderung der Wissenschaftlichen Forschung
(Z 312-B27, Wittgenstein award; P 36232-B), all to P.J., and a DOC fellowship of
the Austrian Academy of Sciences to J.-J.C.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: JingJing
full_name: Chen, JingJing
id: 2C4E65C8-F248-11E8-B48F-1D18A9856A87
last_name: Chen
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Chong
full_name: Chen, Chong
id: 3DFD581A-F248-11E8-B48F-1D18A9856A87
last_name: Chen
- first_name: Itaru
full_name: Arai, Itaru
id: 32A73F6C-F248-11E8-B48F-1D18A9856A87
last_name: Arai
- first_name: Olena
full_name: Kim, Olena
id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87
last_name: Kim
orcid: 0000-0003-2344-1039
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Chen J, Kaufmann W, Chen C, et al. Developmental transformation of Ca2+ channel-vesicle
nanotopography at a central GABAergic synapse. Neuron. 2024;112(5):755-771.e9.
doi:10.1016/j.neuron.2023.12.002
apa: Chen, J., Kaufmann, W., Chen, C., Arai, itaru, Kim, O., Shigemoto, R., &
Jonas, P. M. (2024). Developmental transformation of Ca2+ channel-vesicle nanotopography
at a central GABAergic synapse. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2023.12.002
chicago: Chen, JingJing, Walter Kaufmann, Chong Chen, itaru Arai, Olena Kim, Ryuichi
Shigemoto, and Peter M Jonas. “Developmental Transformation of Ca2+ Channel-Vesicle
Nanotopography at a Central GABAergic Synapse.” Neuron. Elsevier, 2024.
https://doi.org/10.1016/j.neuron.2023.12.002.
ieee: J. Chen et al., “Developmental transformation of Ca2+ channel-vesicle
nanotopography at a central GABAergic synapse,” Neuron, vol. 112, no. 5.
Elsevier, p. 755–771.e9, 2024.
ista: Chen J, Kaufmann W, Chen C, Arai itaru, Kim O, Shigemoto R, Jonas PM. 2024.
Developmental transformation of Ca2+ channel-vesicle nanotopography at a central
GABAergic synapse. Neuron. 112(5), 755–771.e9.
mla: Chen, JingJing, et al. “Developmental Transformation of Ca2+ Channel-Vesicle
Nanotopography at a Central GABAergic Synapse.” Neuron, vol. 112, no. 5,
Elsevier, 2024, p. 755–771.e9, doi:10.1016/j.neuron.2023.12.002.
short: J. Chen, W. Kaufmann, C. Chen, itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas,
Neuron 112 (2024) 755–771.e9.
corr_author: '1'
date_created: 2024-01-21T23:00:56Z
date_published: 2024-03-06T00:00:00Z
date_updated: 2026-09-13T22:30:32Z
day: '06'
ddc:
- '570'
department:
- _id: PeJo
- _id: EM-Fac
- _id: RySh
doi: 10.1016/j.neuron.2023.12.002
ec_funded: 1
external_id:
isi:
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issue: '5'
language:
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oa: 1
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page: 755-771.e9
pmid: 1
project:
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call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: Synaptic communication in neuronal microcircuits
- _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5
grant_number: P36232
name: Mechanisms of GABA release in hippocampal circuits
- _id: 26B66A3E-B435-11E9-9278-68D0E5697425
grant_number: '25383'
name: Development of nanodomain coupling between Ca2+ channels and release sensors
at a central inhibitory synapse
publication: Neuron
publication_identifier:
eissn:
- 1097-4199
issn:
- 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on ISTA Website
relation: press_release
url: https://ista.ac.at/en/news/synapses-brought-to-the-point/
record:
- id: '15101'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Developmental transformation of Ca2+ channel-vesicle nanotopography at a central
GABAergic synapse
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 112
year: '2024'
...
---
OA_place: publisher
_id: '18471'
abstract:
- lang: eng
text: "Spatial omics technologies are enriching our understanding of complex biological
samples, by\r\nallowing us to study their molecular composition while preserving
the spatial relationships\r\nbetween molecules in their native context. As the
field continues to advance, there are\r\ntechnical challenges that need to be
addressed in order to take full advantage of the spatial\r\ncapabilities of these
methods. In this work, I present two technical developments that I\r\nestablished
for multiplexed error robust FISH (MERFISH) throughout my PhD: (1) pushing the\r\nspatial
resolution limits to the nanoscale, and (2) adding rich tissue context to the
mouse brain\r\ntranscriptome. To achieve nanoscale resolution with MERFISH in
cultured cells, I combined it\r\nwith stimulated emission depletion (STED) and
expansion microscopy (ExM) to achieve a\r\nspatial resolution as low as ~20 nm,
and explored the compatibility of MERFISH with singlemolecule localization microscopy
(SMLM) techniques. To visualize targeted mRNAs in mouse\r\nbrain tissue, I applied
the comprehensive analysis of tissues across scales (CATS) toolbox, which\r\nprovides
an unbiased morphological readout by labeling the extracellular domain. I\r\nsuccessfully
established this method, which we call CATS-MERFISH-ExM, to work with thick\r\nmouse
brain slices, being able to extract transcriptomics information with 3D tissue
context.\r\nCATS-MERFISH-ExM enabled us to identify cell types and further visualize
the subcellular\r\ndistribution of transcripts in mouse brain tissue, shedding
light on the neuropil-specific\r\ntranscriptome. This method provides integrated
information on cellular structure and\r\ntranscriptomes in situ, and could potentially
be applied with other modalities, opening new\r\navenues for scientific discovery. "
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
- _id: M-Shop
- _id: ScienComp
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Nathalie
full_name: Agudelo Duenas, Nathalie
id: 40E7F008-F248-11E8-B48F-1D18A9856A87
last_name: Agudelo Duenas
citation:
ama: Agudelo Duenas N. Visualizing the neuronal transcriptional landscape with tissue
context. 2024. doi:10.15479/at:ista:18471
apa: Agudelo Duenas, N. (2024). Visualizing the neuronal transcriptional landscape
with tissue context. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:18471
chicago: Agudelo Duenas, Nathalie. “Visualizing the Neuronal Transcriptional Landscape
with Tissue Context.” Institute of Science and Technology Austria, 2024. https://doi.org/10.15479/at:ista:18471.
ieee: N. Agudelo Duenas, “Visualizing the neuronal transcriptional landscape with
tissue context,” Institute of Science and Technology Austria, 2024.
ista: Agudelo Duenas N. 2024. Visualizing the neuronal transcriptional landscape
with tissue context. Institute of Science and Technology Austria.
mla: Agudelo Duenas, Nathalie. Visualizing the Neuronal Transcriptional Landscape
with Tissue Context. Institute of Science and Technology Austria, 2024, doi:10.15479/at:ista:18471.
short: N. Agudelo Duenas, Visualizing the Neuronal Transcriptional Landscape with
Tissue Context, Institute of Science and Technology Austria, 2024.
corr_author: '1'
date_created: 2024-10-26T20:02:42Z
date_published: 2024-10-28T00:00:00Z
date_updated: 2026-04-14T08:34:37Z
day: '28'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: JoDa
doi: 10.15479/at:ista:18471
ec_funded: 1
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language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: '97'
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232
name: Molecular Drug Targets
publication_identifier:
isbn:
- 978-3-99078-044-2
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
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: Visualizing the neuronal transcriptional landscape with tissue context
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: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
OA_embargo: '12'
OA_place: publisher
_id: '18574'
abstract:
- lang: eng
text: "Biological vision is unlike a camera; rather than transmitting light information
faithfully, early\r\nvisual circuits process the visual scene to convey only the
relevant information in an efficient\r\nmanner. Consequentially, the nature of
this visual processing then depends on what is the\r\nrelevant information in
a scene and on the notion of efficiency. In this work, I study how visual\r\nprocessing
is modulated by two different variations in the visual scene. First, I discovered
that\r\nin the mouse (Mus musculus) retina, Retinal Ganglion Cells in the upper
and lower visual\r\nfield have differences in the center surround structure of
their receptive fields. Comparison\r\nwith models of efficient coding show that
this adaptation likely evolved to cope with the\r\nbrightness gradient from the
sky to the ground that is pervasive in natural scenes. In the\r\nsecond project,
I study how the downstream neurons in the Superior Colliculus dynamically\r\nchange
their temporal selectivity depending on the ambient luminance and behavioral state.\r\nAs
the scene gets darker or when the animal is is less aroused, the neuronal responses
get\r\nlaggier, while still maintaining their relative timing with respect to
the population. Overall, this\r\nwork emphasises the need to understand visual
processing in the context of specific demands\r\nof the animal in its the environment.
The adaptive changes in the visual system, from the\r\nretinal ganglion cells
to the superior colliculus, highlight the intricate ways in which biological\r\nvision
optimizes the processing of visual information.\r\n"
acknowledged_ssus:
- _id: Bio
- _id: ScienComp
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
- _id: E-Lib
acknowledgement: "This work would have been impossible without the Scientific Service
Units of IST Austria. The resources and expertise provided by Scientific Computing
(especially Alois Schlögl), the MIBA Machine Shop (especially Todor Asenov), the
Preclinical Facility (especially Freyja Langer), the Library, the Lab Support Facility
and the Imaging and Optics Facility were the essential bedrock I could build upon.
I would also like to thank IT support at ISTA for powering through remote work and
a cyberattack.\r\nI am grateful for having been funded initially by the European
Union Horizon 2020 Marie Skłodowska-Curie grant 665385 and later by Prof. Maximilian
Joesch's the European Research Council Starting (756502) and Consolidator (101086580)
Grants."
alternative_title:
- ISTA Thesis
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
citation:
ama: Gupta D. Visual adaptations to natural statistics. 2024. doi:10.15479/at:ista:18574
apa: Gupta, D. (2024). Visual adaptations to natural statistics. Institute
of Science and Technology Austria. https://doi.org/10.15479/at:ista:18574
chicago: Gupta, Divyansh. “Visual Adaptations to Natural Statistics.” Institute
of Science and Technology Austria, 2024. https://doi.org/10.15479/at:ista:18574.
ieee: D. Gupta, “Visual adaptations to natural statistics,” Institute of Science
and Technology Austria, 2024.
ista: Gupta D. 2024. Visual adaptations to natural statistics. Institute of Science
and Technology Austria.
mla: Gupta, Divyansh. Visual Adaptations to Natural Statistics. Institute
of Science and Technology Austria, 2024, doi:10.15479/at:ista:18574.
short: D. Gupta, Visual Adaptations to Natural Statistics, Institute of Science
and Technology Austria, 2024.
corr_author: '1'
date_created: 2024-11-20T21:30:44Z
date_published: 2024-11-22T00:00:00Z
date_updated: 2026-04-07T13:24:48Z
day: '22'
ddc:
- '573'
degree_awarded: PhD
department:
- _id: GradSch
- _id: MaJö
doi: 10.15479/at:ista:18574
ec_funded: 1
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date_created: 2024-11-25T14:44:03Z
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file_date_updated: 2025-11-11T23:30:02Z
fulldoi: https://doi.org/10.15479/at:ista:18574
has_accepted_license: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-sa/4.0/
month: '11'
oa: 1
oa_version: Published Version
page: '86'
project:
- _id: bdaf81a8-d553-11ed-ba76-c95961984540
grant_number: '101086580'
name: 'Action Selection in the Midbrain: Neuromodulation of Visuomotor Senses'
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
- _id: 2634E9D2-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '756502'
name: Circuits of Visual Attention
publication_identifier:
isbn:
- 978-3-99078-050-3
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '12349'
relation: part_of_dissertation
status: public
- id: '12370'
relation: research_data
status: public
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: Visual adaptations to natural statistics
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: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
_id: '15323'
abstract:
- lang: eng
text: Supercomplexes of the respiratory chain are established constituents of the
oxidative phosphorylation system, but their role in mammalian metabolism has been
hotly debated. Although recent studies have shown that different tissues/organs
are equipped with specific sets of supercomplexes, depending on their metabolic
needs, the notion that supercomplexes have a role in the regulation of metabolism
has been challenged. However, irrespective of the mechanistic conclusions, the
composition of various high molecular weight supercomplexes remains uncertain.
Here, using cryogenic electron microscopy, we demonstrate that mammalian (mouse)
tissues contain three defined types of ‘respirasome’, supercomplexes made of CI,
CIII2 and CIV. The stoichiometry and position of CIV differs in the three respirasomes,
of which only one contains the supercomplex-associated factor SCAF1, whose involvement
in respirasome formation has long been contended. Our structures confirm that
the ‘canonical’ respirasome (the C-respirasome, CICIII2CIV) does not contain SCAF1,
which is instead associated to a different respirasome (the CS-respirasome), containing
a second copy of CIV. We also identify an alternative respirasome (A-respirasome),
with CIV bound to the ‘back’ of CI, instead of the ‘toe’. This structural characterization
of mouse mitochondrial supercomplexes allows us to hypothesize a mechanistic basis
for their specific role in different metabolic conditions.
acknowledged_ssus:
- _id: EM-Fac
- _id: LifeSc
- _id: PreCl
- _id: ScienComp
acknowledgement: Supercomplexes of the respiratory chain are established constituents
of the oxidative phosphorylation system, but their role in mammalian metabolism
has been hotly debated. Although recent studies have shown that different tissues/organs
are equipped with specific sets of supercomplexes, depending on their metabolic
needs, the notion that supercomplexes have a role in the regulation of metabolism
has been challenged. However, irrespective of the mechanistic conclusions, the composition
of various high molecular weight supercomplexes remains uncertain. Here, using cryogenic
electron microscopy, we demonstrate that mammalian (mouse) tissues contain three
defined types of ‘respirasome’, supercomplexes made of CI, CIII2 and CIV. The stoichiometry
and position of CIV differs in the three respirasomes, of which only one contains
the supercomplex-associated factor SCAF1, whose involvement in respirasome formation
has long been contended. Our structures confirm that the ‘canonical’ respirasome
(the C-respirasome, CICIII2CIV) does not contain SCAF1, which is instead associated
to a different respirasome (the CS-respirasome), containing a second copy of CIV.
We also identify an alternative respirasome (A-respirasome), with CIV bound to the
‘back’ of CI, instead of the ‘toe’. This structural characterization of mouse mitochondrial
supercomplexes allows us to hypothesize a mechanistic basis for their specific role
in different metabolic conditions.
article_processing_charge: No
article_type: original
author:
- first_name: Irene
full_name: Vercellino, Irene
id: 3ED6AF16-F248-11E8-B48F-1D18A9856A87
last_name: Vercellino
orcid: 0000-0001-5618-3449
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
citation:
ama: Vercellino I, Sazanov LA. SCAF1 drives the compositional diversity of mammalian
respirasomes. Nature Structural and Molecular Biology. 2024;31:1061-1071.
doi:10.1038/s41594-024-01255-0
apa: Vercellino, I., & Sazanov, L. A. (2024). SCAF1 drives the compositional
diversity of mammalian respirasomes. Nature Structural and Molecular Biology.
Springer Nature. https://doi.org/10.1038/s41594-024-01255-0
chicago: Vercellino, Irene, and Leonid A Sazanov. “SCAF1 Drives the Compositional
Diversity of Mammalian Respirasomes.” Nature Structural and Molecular Biology.
Springer Nature, 2024. https://doi.org/10.1038/s41594-024-01255-0.
ieee: I. Vercellino and L. A. Sazanov, “SCAF1 drives the compositional diversity
of mammalian respirasomes,” Nature Structural and Molecular Biology, vol.
31. Springer Nature, pp. 1061–1071, 2024.
ista: Vercellino I, Sazanov LA. 2024. SCAF1 drives the compositional diversity of
mammalian respirasomes. Nature Structural and Molecular Biology. 31, 1061–1071.
mla: Vercellino, Irene, and Leonid A. Sazanov. “SCAF1 Drives the Compositional Diversity
of Mammalian Respirasomes.” Nature Structural and Molecular Biology, vol.
31, Springer Nature, 2024, pp. 1061–71, doi:10.1038/s41594-024-01255-0.
short: I. Vercellino, L.A. Sazanov, Nature Structural and Molecular Biology 31 (2024)
1061–1071.
corr_author: '1'
date_created: 2024-04-14T22:01:03Z
date_published: 2024-07-01T00:00:00Z
date_updated: 2025-11-24T08:35:04Z
day: '01'
ddc:
- '572'
department:
- _id: LeSa
doi: 10.1038/s41594-024-01255-0
ec_funded: 1
external_id:
isi:
- '001196897300001'
pmid:
- '38575788'
file:
- access_level: open_access
checksum: 21f05d188762acd7f49a97f3d09c8d9f
content_type: application/pdf
creator: lsazanov
date_created: 2024-05-14T11:57:56Z
date_updated: 2025-01-01T23:30:03Z
embargo: 2025-01-01
file_id: '15392'
file_name: megacomplex_submit_NSMB_withFigures.pdf
file_size: 24424729
relation: main_file
file_date_updated: 2025-01-01T23:30:03Z
fulldoi: https://doi.org/10.1038/s41594-024-01255-0
has_accepted_license: '1'
intvolume: ' 31'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Submitted Version
page: 1061-1071
pmid: 1
project:
- _id: 627abdeb-2b32-11ec-9570-ec31a97243d3
call_identifier: H2020
grant_number: '101020697'
name: Structure and mechanism of respiratory chain molecular machines
publication: Nature Structural and Molecular Biology
publication_identifier:
eissn:
- 1545-9985
issn:
- 1545-9993
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: erratum
url: https://doi.org/10.1038/s41594-025-01721-3
scopus_import: '1'
status: public
title: SCAF1 drives the compositional diversity of mammalian respirasomes
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: 31
year: '2024'
...
---
APC_amount: 5887,8 EUR
OA_place: publisher
OA_type: hybrid
_id: '15084'
abstract:
- lang: eng
text: "GABAB receptor (GBR) activation inhibits neurotransmitter release in axon
terminals in the brain, except in medial habenula (MHb) terminals, which show
robust potentiation. However, mechanisms underlying this enigmatic potentiation
remain elusive. Here, we report that GBR activation on MHb terminals induces an
activity-dependent transition from a facilitating, tonic to a depressing, phasic
neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase
in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked
synaptic vesicles (SVs) at the presynaptic active zone (AZ). Strikingly, the depressing
phasic release exhibits looser coupling distance than the tonic release. Furthermore,
the tonic and phasic release are selectively affected by deletion of synaptoporin
(SPO) and Ca\r\n 2+\r\n -dependent
activator protein for secretion 2 (CAPS2), respectively. SPO modulates augmentation,
the short-term plasticity associated with tonic release, and CAPS2 retains the
increased RRP for initial responses in phasic response trains. The cytosolic protein
CAPS2 showed a SV-associated distribution similar to the vesicular transmembrane
protein SPO, and they were colocalized in the same terminals. We developed the
“Flash and Freeze-fracture” method, and revealed the release of SPO-associated
vesicles in both tonic and phasic modes and activity-dependent recruitment of
CAPS2 to the AZ during phasic release, which lasted several minutes. Overall,
these results indicate that GBR activation translocates CAPS2 to the AZ along
with the fusion of CAPS2-associated SVs, contributing to persistency of the RRP
increase. Thus, we identified structural and molecular mechanisms underlying tonic
and phasic neurotransmitter release and their transition by GBR activation in
MHb terminals."
acknowledged_ssus:
- _id: M-Shop
- _id: PreCl
- _id: EM-Fac
acknowledgement: We thank Erwin Neher and Ipe Ninan for critical comments on the manuscript.
This project has received funding from the European Research Council (ERC) and European
Commission, under the European Union’s Horizon 2020 research and innovation program
(ERC grant agreement no. 694539 to R.S. and the Marie Skłodowska-Curie grant agreement
no. 665385 to C.Ö.). This study was supported by the Cooperative Study Program of
Center for Animal Resources and Collaborative Study of NINS. We thank Kohgaku Eguchi
for statistical analysis, Yu Kasugai for additional EM imaging, Robert Beattie for
the design of the slice recovery chamber for Flash and Freeze experiments, Todor
Asenov from the ISTA machine shop for custom part preparations for high-pressure
freezing, the ISTA preclinical facility for animal caretaking, and the ISTA EM facilities
for technical support.
article_number: e2301449121
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Peter
full_name: Koppensteiner, Peter
id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
last_name: Koppensteiner
orcid: 0000-0002-3509-1948
- first_name: Pradeep
full_name: Bhandari, Pradeep
id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87
last_name: Bhandari
orcid: 0000-0003-0863-4481
- first_name: Hüseyin C
full_name: Önal, Hüseyin C
id: 4659D740-F248-11E8-B48F-1D18A9856A87
last_name: Önal
orcid: 0000-0002-2771-2011
- first_name: Carolina
full_name: Borges Merjane, Carolina
id: 4305C450-F248-11E8-B48F-1D18A9856A87
last_name: Borges Merjane
orcid: 0000-0003-0005-401X
- first_name: Elodie
full_name: Le Monnier, Elodie
id: 3B59276A-F248-11E8-B48F-1D18A9856A87
last_name: Le Monnier
- first_name: Utsa
full_name: Roy, Utsa
id: 4d26cf11-5355-11ee-ae5a-eb05e255b9b2
last_name: Roy
- first_name: Yukihiro
full_name: Nakamura, Yukihiro
last_name: Nakamura
- first_name: Tetsushi
full_name: Sadakata, Tetsushi
last_name: Sadakata
- first_name: Makoto
full_name: Sanbo, Makoto
last_name: Sanbo
- first_name: Masumi
full_name: Hirabayashi, Masumi
last_name: Hirabayashi
- first_name: JeongSeop
full_name: Rhee, JeongSeop
last_name: Rhee
- first_name: Nils
full_name: Brose, Nils
last_name: Brose
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
citation:
ama: Koppensteiner P, Bhandari P, Önal C, et al. GABAB receptors induce phasic release
from medial habenula terminals through activity-dependent recruitment of release-ready
vesicles. Proceedings of the National Academy of Sciences of the United States
of America. 2024;121(8). doi:10.1073/pnas.2301449121
apa: Koppensteiner, P., Bhandari, P., Önal, C., Borges Merjane, C., Le Monnier,
E., Roy, U., … Shigemoto, R. (2024). GABAB receptors induce phasic release from
medial habenula terminals through activity-dependent recruitment of release-ready
vesicles. Proceedings of the National Academy of Sciences of the United States
of America. National Academy of Sciences. https://doi.org/10.1073/pnas.2301449121
chicago: Koppensteiner, Peter, Pradeep Bhandari, Cihan Önal, Carolina Borges Merjane,
Elodie Le Monnier, Utsa Roy, Yukihiro Nakamura, et al. “GABAB Receptors Induce
Phasic Release from Medial Habenula Terminals through Activity-Dependent Recruitment
of Release-Ready Vesicles.” Proceedings of the National Academy of Sciences
of the United States of America. National Academy of Sciences, 2024. https://doi.org/10.1073/pnas.2301449121.
ieee: P. Koppensteiner et al., “GABAB receptors induce phasic release from
medial habenula terminals through activity-dependent recruitment of release-ready
vesicles,” Proceedings of the National Academy of Sciences of the United States
of America, vol. 121, no. 8. National Academy of Sciences, 2024.
ista: Koppensteiner P, Bhandari P, Önal C, Borges Merjane C, Le Monnier E, Roy U,
Nakamura Y, Sadakata T, Sanbo M, Hirabayashi M, Rhee J, Brose N, Jonas PM, Shigemoto
R. 2024. GABAB receptors induce phasic release from medial habenula terminals
through activity-dependent recruitment of release-ready vesicles. Proceedings
of the National Academy of Sciences of the United States of America. 121(8), e2301449121.
mla: Koppensteiner, Peter, et al. “GABAB Receptors Induce Phasic Release from Medial
Habenula Terminals through Activity-Dependent Recruitment of Release-Ready Vesicles.”
Proceedings of the National Academy of Sciences of the United States of America,
vol. 121, no. 8, e2301449121, National Academy of Sciences, 2024, doi:10.1073/pnas.2301449121.
short: P. Koppensteiner, P. Bhandari, C. Önal, C. Borges Merjane, E. Le Monnier,
U. Roy, Y. Nakamura, T. Sadakata, M. Sanbo, M. Hirabayashi, J. Rhee, N. Brose,
P.M. Jonas, R. Shigemoto, Proceedings of the National Academy of Sciences of the
United States of America 121 (2024).
corr_author: '1'
date_created: 2024-03-05T09:23:55Z
date_published: 2024-02-20T00:00:00Z
date_updated: 2026-09-13T22:30:36Z
day: '20'
ddc:
- '570'
department:
- _id: RySh
- _id: PeJo
doi: 10.1073/pnas.2301449121
ec_funded: 1
external_id:
isi:
- '001208567300006'
pmid:
- '38346189'
file:
- access_level: open_access
checksum: b25b2a057c266ff317a48b0d54d6fc8a
content_type: application/pdf
creator: dernst
date_created: 2024-03-12T13:42:42Z
date_updated: 2024-03-12T13:42:42Z
file_id: '15110'
file_name: 2024_PNAS_Koppensteiner.pdf
file_size: 13648221
relation: main_file
success: 1
file_date_updated: 2024-03-12T13:42:42Z
fulldoi: https://doi.org/10.1073/pnas.2301449121
has_accepted_license: '1'
intvolume: ' 121'
isi: 1
issue: '8'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25CA28EA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '694539'
name: 'In situ analysis of single channel subunit composition in neurons: physiological
implication in synaptic plasticity and behaviour'
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication: Proceedings of the National Academy of Sciences of the United States
of America
publication_identifier:
eissn:
- 1091-6490
issn:
- 0027-8424
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
link:
- description: News on ISTA Website
relation: press_release
url: https://ista.ac.at/en/news/neuronal-insights-flash-and-freeze-fracture/
record:
- id: '13173'
relation: research_data
status: public
- id: '19271'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: GABAB receptors induce phasic release from medial habenula terminals through
activity-dependent recruitment of release-ready vesicles
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 121
year: '2024'
...
---
APC_amount: 6248,82 EUR
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '18603'
abstract:
- lang: eng
text: It is widely believed that information storage in neuronal circuits involves
nanoscopic structural changes at synapses, resulting in the formation of synaptic
engrams. However, direct evidence for this hypothesis is lacking. To test this
conjecture, we combined chemical potentiation, functional analysis by paired pre-postsynaptic
recordings, and structural analysis by electron microscopy (EM) and freeze-fracture
replica labeling (FRL) at the rodent hippocampal mossy fiber synapse, a key synapse
in the trisynaptic circuit of the hippocampus. Biophysical analysis of synaptic
transmission revealed that forskolin-induced chemical potentiation increased the
readily releasable vesicle pool size and vesicular release probability by 146%
and 49%, respectively. Structural analysis of mossy fiber synapses by EM and FRL
demonstrated an increase in the number of vesicles close to the plasma membrane
and the number of clusters of the priming protein Munc13-1, indicating an increase
in the number of both docked and primed vesicles. Furthermore, FRL analysis revealed
a significant reduction of the distance between Munc13-1 and CaV2.1 Ca2+ channels,
suggesting reconfiguration of the channel-vesicle coupling nanotopography. Our
results indicate that presynaptic plasticity is associated with structural reorganization
of active zones. We propose that changes in potential nanoscopic organization
at synaptic vesicle release sites may be correlates of learning and memory at
a plastic central synapse.
acknowledged_ssus:
- _id: EM-Fac
- _id: PreCl
acknowledgement: "We thank Carolina Borges-Merjane, Jing-Jing Chen, Katharina Lichter,
and Samuel Young for critically reading the manuscript; the Electron Microscopy
Facility of ISTA, in particular Vanessa Zheden, for extensive support, advice, and
experimental assistance; the Preclinical Facility of ISTA, in particular Victoria
Wimmer and Michael Schunn, for experimental assistance; Florian Marr and Christina
Altmutter for technical support; Alois Schlögl for help with analysis; and Eleftheria
Kralli-Beller for manuscript editing. We also thank Cordelia Imig for providing
Munc13-1cKO-Munc13-2/3(−/−) mutant mice. Part of the work has been published in
O.K.’s thesis in partial fulfillment of the requirements for the degree of Doctor
of Philosophy.\r\nThis project received funding from the European Research Council
and European Union’s Horizon 2020 research and innovation programme (ERC 692692
to P.J.; https://cordis.europa.eu/project/id/692692/de) and from the Fond zur Förderung
der Wissenschaftlichen Forschung (Z312-B27 Wittgenstein award to P.J., https://www.fwf.ac.at/en/funding/portfolio/projects/fwf-wittgenstein-award;
W1205-B09 and P36232-B to P.J., https://www.fwf.ac.at/en/funding; I6166-B to R.S.;
https://www.fwf.ac.at/en/funding). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the manuscript."
article_number: e3002879
article_processing_charge: Yes
article_type: original
author:
- first_name: Olena
full_name: Kim, Olena
id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87
last_name: Kim
orcid: 0000-0003-2344-1039
- first_name: Yuji
full_name: Okamoto, Yuji
id: 3337E116-F248-11E8-B48F-1D18A9856A87
last_name: Okamoto
orcid: 0000-0003-0408-6094
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Nils
full_name: Brose, Nils
last_name: Brose
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Kim O, Okamoto Y, Kaufmann W, Brose N, Shigemoto R, Jonas PM. Presynaptic cAMP-PKA-mediated
potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle
coupling at hippocampal mossy fiber boutons. PLoS Biology. 2024;22(11).
doi:10.1371/journal.pbio.3002879
apa: Kim, O., Okamoto, Y., Kaufmann, W., Brose, N., Shigemoto, R., & Jonas,
P. M. (2024). Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration
of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber
boutons. PLoS Biology. Public Library of Science. https://doi.org/10.1371/journal.pbio.3002879
chicago: Kim, Olena, Yuji Okamoto, Walter Kaufmann, Nils Brose, Ryuichi Shigemoto,
and Peter M Jonas. “Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration
of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber
Boutons.” PLoS Biology. Public Library of Science, 2024. https://doi.org/10.1371/journal.pbio.3002879.
ieee: O. Kim, Y. Okamoto, W. Kaufmann, N. Brose, R. Shigemoto, and P. M. Jonas,
“Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic
vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons,”
PLoS Biology, vol. 22, no. 11. Public Library of Science, 2024.
ista: Kim O, Okamoto Y, Kaufmann W, Brose N, Shigemoto R, Jonas PM. 2024. Presynaptic
cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools
and channel-vesicle coupling at hippocampal mossy fiber boutons. PLoS Biology.
22(11), e3002879.
mla: Kim, Olena, et al. “Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration
of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber
Boutons.” PLoS Biology, vol. 22, no. 11, e3002879, Public Library of Science,
2024, doi:10.1371/journal.pbio.3002879.
short: O. Kim, Y. Okamoto, W. Kaufmann, N. Brose, R. Shigemoto, P.M. Jonas, PLoS
Biology 22 (2024).
corr_author: '1'
date_created: 2024-12-01T23:01:54Z
date_published: 2024-11-18T00:00:00Z
date_updated: 2026-04-16T12:20:34Z
day: '18'
ddc:
- '570'
department:
- _id: PeJo
- _id: EM-Fac
- _id: RySh
doi: 10.1371/journal.pbio.3002879
ec_funded: 1
external_id:
isi:
- '001358568700003'
pmid:
- '39556620'
file:
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checksum: 7de2dcb50deb65dde05c80082bb85a82
content_type: application/pdf
creator: dernst
date_created: 2024-12-03T08:56:53Z
date_updated: 2024-12-03T08:56:53Z
file_id: '18608'
file_name: 2024_PloSBio_Kim.pdf
file_size: 3057631
relation: main_file
success: 1
file_date_updated: 2024-12-03T08:56:53Z
fulldoi: https://doi.org/10.1371/journal.pbio.3002879
has_accepted_license: '1'
intvolume: ' 22'
isi: 1
issue: '11'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: Synaptic communication in neuronal microcircuits
- _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5
grant_number: P36232
name: Mechanisms of GABA release in hippocampal circuits
- _id: b1b85715-d554-11ed-a5ad-84a07fc9f18e
grant_number: I06166
name: Structural & functional basis of presynaptic plasticity
- _id: 25C3DBB6-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W01205
name: Zellkommunikation in Gesundheit und Krankheit
- _id: 3AC91DDA-15DF-11EA-824D-93A3E7B544D1
call_identifier: FWF
name: FWF Open Access Fund
publication: PLoS Biology
publication_identifier:
eissn:
- 1545-7885
issn:
- 1544-9173
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
related_material:
record:
- id: '18296'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic
vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 22
year: '2024'
...
---
OA_place: publisher
_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:10.15479/at:ista:12716
apa: 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. https://doi.org/10.15479/at:ista:12716
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. https://doi.org/10.15479/at:ista:12716.
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. 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,
doi:10.15479/at:ista:12716.
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.
corr_author: '1'
date_created: 2023-03-08T15:19:45Z
date_published: 2023-03-10T00:00:00Z
date_updated: 2026-04-07T13:25:15Z
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'
file_name: Burnett_Thesis_2023.docx
file_size: 23029260
relation: source_file
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checksum: cebc77705288bf4382db9b3541483cd0
content_type: application/pdf
creator: lburnett
date_created: 2023-03-08T15:08:46Z
date_updated: 2023-03-08T15:08:46Z
file_id: '12718'
file_name: Burnett_Thesis_2023_pdfA.pdf
file_size: 11959869
relation: main_file
success: 1
file_date_updated: 2023-03-08T15:08:46Z
fulldoi: https://doi.org/10.15479/at:ista:12716
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: ba8df636-2132-11f1-aed0-ed93e2281fdd
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. Cell. 2023;186(9):1950-1967.e25. doi:10.1016/j.cell.2023.02.037
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. Cell. Elsevier. https://doi.org/10.1016/j.cell.2023.02.037
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.” Cell. Elsevier,
2023. https://doi.org/10.1016/j.cell.2023.02.037.
ieee: L. Knaus et al., “Large neutral amino acid levels tune perinatal neuronal
excitability and survival,” Cell, 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.” Cell, vol. 186, no. 9, Elsevier, 2023, p. 1950–1967.e25,
doi:10.1016/j.cell.2023.02.037.
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.
corr_author: '1'
date_created: 2023-04-05T08:15:40Z
date_published: 2023-04-27T00:00:00Z
date_updated: 2026-04-14T08:34:36Z
day: '27'
ddc:
- '570'
department:
- _id: SiHi
- _id: GaNo
doi: 10.1016/j.cell.2023.02.037
ec_funded: 1
external_id:
isi:
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pmid:
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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
pmid: 1
project:
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232
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:
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relation: dissertation_contains
status: public
- 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 186
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:10.15479/AT:ISTA:12817
apa: Danzl, J. G. (2023). Research data for the publication “Dense 4D nanoscale
reconstruction of living brain tissue.” Institute of Science and Technology Austria.
https://doi.org/10.15479/AT:ISTA:12817
chicago: Danzl, Johann G. “Research Data for the Publication ‘Dense 4D Nanoscale
Reconstruction of Living Brain Tissue.’” Institute of Science and Technology Austria,
2023. https://doi.org/10.15479/AT:ISTA:12817.
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, 10.15479/AT:ISTA:12817.
mla: Danzl, Johann G. Research Data for the Publication “Dense 4D Nanoscale Reconstruction
of Living Brain Tissue.” Institute of Science and Technology Austria, 2023,
doi:10.15479/AT:ISTA:12817.
short: J.G. Danzl, (2023).
contributor:
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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
corr_author: '1'
date_created: 2023-04-07T11:37:40Z
date_published: 2023-05-19T00:00:00Z
date_updated: 2026-04-14T08:34:34Z
day: '19'
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fulldoi: https://doi.org/10.15479/AT:ISTA:12817
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month: '05'
oa: 1
oa_version: Published Version
publisher: Institute of Science and Technology Austria
related_material:
record:
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relation: used_in_publication
status: public
status: public
title: Research data for the publication "Dense 4D nanoscale reconstruction of living
brain tissue"
tmp:
image: /images/cc_by_sa.png
legal_code_url: https://creativecommons.org/licenses/by-sa/4.0/legalcode
name: Creative Commons Attribution-ShareAlike 4.0 International Public License (CC
BY-SA 4.0)
short: CC BY-SA (4.0)
type: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2023'
...
---
_id: '12830'
abstract:
- lang: eng
text: Interstitial fluid (IF) accumulation between embryonic cells is thought to
be important for embryo patterning and morphogenesis. Here, we identify a positive
mechanical feedback loop between cell migration and IF relocalization and find
that it promotes embryonic axis formation during zebrafish gastrulation. We show
that anterior axial mesendoderm (prechordal plate [ppl]) cells, moving in between
the yolk cell and deep cell tissue to extend the embryonic axis, compress the
overlying deep cell layer, thereby causing IF to flow from the deep cell layer
to the boundary between the yolk cell and the deep cell layer, directly ahead
of the advancing ppl. This IF relocalization, in turn, facilitates ppl cell protrusion
formation and migration by opening up the space into which the ppl moves and,
thereby, the ability of the ppl to trigger IF relocalization by pushing against
the overlying deep cell layer. Thus, embryonic axis formation relies on a hydraulic
feedback loop between cell migration and IF relocalization.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
acknowledgement: We thank Andrea Pauli (IMP) and Edouard Hannezo (ISTA) for fruitful
discussions and support with the SPIM experiments; the Heisenberg group, and especially
Feyza Nur Arslan and Alexandra Schauer, for discussions and feedback; Michaela Jović
(ISTA) for help with the quantitative real-time PCR protocol; the bioimaging and
zebrafish facilities of ISTA for continuous support; Stephan Preibisch (Janelia
Research Campus) for support with the SPIM data analysis; and Nobuhiro Nakamura
(Tokyo Institute of Technology) for sharing α1-Na+/K+-ATPase antibody. This work
was supported by funding from the European Union (European Research Council Advanced
grant 742573 to C.-P.H.), postdoctoral fellowships from EMBO (LTF-850-2017) and
HFSP (LT000429/2018-L2) to D.P., and a PhD fellowship from the Studienstiftung des
deutschen Volkes to F.P.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Karla
full_name: Huljev, Karla
id: 44C6F6A6-F248-11E8-B48F-1D18A9856A87
last_name: Huljev
- first_name: Shayan
full_name: Shamipour, Shayan
id: 40B34FE2-F248-11E8-B48F-1D18A9856A87
last_name: Shamipour
- first_name: Diana C
full_name: Nunes Pinheiro, Diana C
id: 2E839F16-F248-11E8-B48F-1D18A9856A87
last_name: Nunes Pinheiro
orcid: 0000-0003-4333-7503
- first_name: Friedrich
full_name: Preusser, Friedrich
last_name: Preusser
- first_name: Irene
full_name: Steccari, Irene
id: 2705C766-9FE2-11EA-B224-C6773DDC885E
last_name: Steccari
- 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: Suyash
full_name: Naik, Suyash
id: 2C0B105C-F248-11E8-B48F-1D18A9856A87
last_name: Naik
orcid: 0000-0001-8421-5508
- 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: Huljev K, Shamipour S, Nunes Pinheiro DC, et al. A hydraulic feedback loop
between mesendoderm cell migration and interstitial fluid relocalization promotes
embryonic axis formation in zebrafish. Developmental Cell. 2023;58(7):582-596.e7.
doi:10.1016/j.devcel.2023.02.016
apa: Huljev, K., Shamipour, S., Nunes Pinheiro, D. C., Preusser, F., Steccari, I.,
Sommer, C. M., … Heisenberg, C.-P. J. (2023). A hydraulic feedback loop between
mesendoderm cell migration and interstitial fluid relocalization promotes embryonic
axis formation in zebrafish. Developmental Cell. Elsevier. https://doi.org/10.1016/j.devcel.2023.02.016
chicago: Huljev, Karla, Shayan Shamipour, Diana C Nunes Pinheiro, Friedrich Preusser,
Irene Steccari, Christoph M Sommer, Suyash Naik, and Carl-Philipp J Heisenberg.
“A Hydraulic Feedback Loop between Mesendoderm Cell Migration and Interstitial
Fluid Relocalization Promotes Embryonic Axis Formation in Zebrafish.” Developmental
Cell. Elsevier, 2023. https://doi.org/10.1016/j.devcel.2023.02.016.
ieee: K. Huljev et al., “A hydraulic feedback loop between mesendoderm cell
migration and interstitial fluid relocalization promotes embryonic axis formation
in zebrafish,” Developmental Cell, vol. 58, no. 7. Elsevier, p. 582–596.e7,
2023.
ista: Huljev K, Shamipour S, Nunes Pinheiro DC, Preusser F, Steccari I, Sommer CM,
Naik S, Heisenberg C-PJ. 2023. A hydraulic feedback loop between mesendoderm cell
migration and interstitial fluid relocalization promotes embryonic axis formation
in zebrafish. Developmental Cell. 58(7), 582–596.e7.
mla: Huljev, Karla, et al. “A Hydraulic Feedback Loop between Mesendoderm Cell Migration
and Interstitial Fluid Relocalization Promotes Embryonic Axis Formation in Zebrafish.”
Developmental Cell, vol. 58, no. 7, Elsevier, 2023, p. 582–596.e7, doi:10.1016/j.devcel.2023.02.016.
short: K. Huljev, S. Shamipour, D.C. Nunes Pinheiro, F. Preusser, I. Steccari, C.M.
Sommer, S. Naik, C.-P.J. Heisenberg, Developmental Cell 58 (2023) 582–596.e7.
corr_author: '1'
date_created: 2023-04-16T22:01:07Z
date_published: 2023-04-10T00:00:00Z
date_updated: 2025-04-23T08:51:34Z
day: '10'
ddc:
- '570'
department:
- _id: CaHe
- _id: Bio
doi: 10.1016/j.devcel.2023.02.016
ec_funded: 1
external_id:
isi:
- '000982111800001'
pmid:
- '36931269'
file:
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has_accepted_license: '1'
intvolume: ' 58'
isi: 1
issue: '7'
language:
- iso: eng
month: '04'
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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
- _id: 26520D1E-B435-11E9-9278-68D0E5697425
grant_number: ALTF 850-2017
name: Coordination of mesendoderm cell fate specification and internalization during
zebrafish gastrulation
- _id: 266BC5CE-B435-11E9-9278-68D0E5697425
grant_number: LT000429
name: Coordination of mesendoderm fate specification and internalization during
zebrafish gastrulation
publication: Developmental Cell
publication_identifier:
eissn:
- 1878-1551
issn:
- 1534-5807
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: A hydraulic feedback loop between mesendoderm cell migration and interstitial
fluid relocalization promotes embryonic axis formation in zebrafish
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: 58
year: '2023'
...
---
OA_place: publisher
_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:10.15479/at:ista:13107'
apa: '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. https://doi.org/10.15479/at:ista:13107'
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. https://doi.org/10.15479/at:ista:13107.'
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. The Metabolism of the Developing Brain : How Large Neutral
Amino Acids Modulate Perinatal Neuronal Excitability and Survival. Institute
of Science and Technology Austria, 2023, doi:10.15479/at:ista:13107.'
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.'
corr_author: '1'
date_created: 2023-06-01T09:05:24Z
date_published: 2023-05-31T00:00:00Z
date_updated: 2026-04-14T08:34:36Z
day: '31'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: GaNo
doi: 10.15479/at:ista:13107
ec_funded: 1
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date_created: 2023-06-01T13:48:41Z
date_updated: 2023-06-01T13:48:41Z
file_id: '13112'
file_name: Thesis_Lisa Knaus_approved_final.docx
file_size: 12991551
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date_created: 2023-06-02T09:47:29Z
date_updated: 2023-06-07T08:41:49Z
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file_name: Thesis_Lisa Knaus_approved_final_pdfa2b.pdf
file_size: 9309015
relation: main_file
file_date_updated: 2023-06-07T08:41:49Z
fulldoi: https://doi.org/10.15479/at:ista:13107
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
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: ba8df636-2132-11f1-aed0-ed93e2281fdd
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:10.15479/AT:ISTA:13126
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. https://doi.org/10.15479/AT:ISTA:13126
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. https://doi.org/10.15479/AT:ISTA:13126.
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,
10.15479/AT:ISTA:13126.
mla: Danzl, Johann G. Research Data for the Publication “Imaging Brain Tissue
Architecture across Millimeter to Nanometer Scales.” Institute of Science
and Technology Austria, 2023, doi:10.15479/AT:ISTA:13126.
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
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file_size: 14639269
relation: main_file
success: 1
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checksum: 327dca11f42d5375d7f47f4cbd5b36c0
content_type: application/octet-stream
creator: jdanzl
date_created: 2023-08-03T15:21:01Z
date_updated: 2023-08-03T15:21:01Z
file_id: '13946'
file_name: model.p
file_size: 279467712
relation: main_file
success: 1
file_date_updated: 2023-08-04T13:19:47Z
fulldoi: https://doi.org/10.15479/AT:ISTA:13126
has_accepted_license: '1'
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: 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: Synaptic communication in neuronal microcircuits
- _id: 23889792-32DE-11EA-91FC-C7463DDC885E
grant_number: LS18-022
name: High content imaging to decode human immune cell interactions in health and
allergic disease
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
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'
...
---
OA_place: publisher
OA_type: free access
_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. Journal of Cell Science. 2023;136(15).
doi:10.1242/jcs.260668
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. Journal of Cell Science. The Company of Biologists. https://doi.org/10.1242/jcs.260668
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.” Journal
of Cell Science. The Company of Biologists, 2023. https://doi.org/10.1242/jcs.260668.
ieee: T. Higashi et al., “ZnUMBA - a live imaging method to detect local
barrier breaches,” Journal of Cell Science, 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.” Journal of Cell Science, vol. 136, no. 15, jcs260668, The Company
of Biologists, 2023, doi:10.1242/jcs.260668.
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: 2025-06-25T06:28:45Z
day: '01'
ddc:
- '570'
department:
- _id: CaHe
- _id: EvBe
doi: 10.1242/jcs.260668
ec_funded: 1
external_id:
isi:
- '001070149000001'
pmid:
- '37461809'
fulldoi: https://doi.org/10.1242/jcs.260668
has_accepted_license: '1'
intvolume: ' 136'
isi: 1
issue: '15'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1242/jcs.260668
month: '08'
oa: 1
oa_version: None
pmid: 1
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: '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.
iScience. 2023;26(10). doi:10.1016/j.isci.2023.107780
apa: Maes, M. E., Colombo, G., Schoot Uiterkamp, F. E., Sternberg, F., Venturino,
A., Pohl, E. E., & Siegert, S. (2023). Mitochondrial network adaptations of
microglia reveal sex-specific stress response after injury and UCP2 knockout.
IScience. Elsevier. https://doi.org/10.1016/j.isci.2023.107780
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.” IScience. Elsevier, 2023. https://doi.org/10.1016/j.isci.2023.107780.
ieee: M. E. Maes et al., “Mitochondrial network adaptations of microglia
reveal sex-specific stress response after injury and UCP2 knockout,” iScience,
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.” IScience,
vol. 26, no. 10, 107780, Elsevier, 2023, doi:10.1016/j.isci.2023.107780.
short: M.E. Maes, G. Colombo, F.E. Schoot Uiterkamp, F. Sternberg, A. Venturino,
E.E. Pohl, S. Siegert, IScience 26 (2023).
corr_author: '1'
date_created: 2023-09-24T22:01:11Z
date_published: 2023-10-20T00:00:00Z
date_updated: 2024-10-09T21:07:01Z
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
fulldoi: https://doi.org/10.1016/j.isci.2023.107780
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:10.15479/AT:ISTA:14644
apa: Tluckova, K., Testa Salmazo, A. P., & Bernecky, C. (n.d.). Mechanism of
mammalian transcriptional repression by noncoding RNA. Institute of Science and
Technology Austria. https://doi.org/10.15479/AT:ISTA:14644
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. https://doi.org/10.15479/AT:ISTA:14644.
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. 10.15479/AT:ISTA:14644.
mla: Tluckova, Katarina, et al. Mechanism of Mammalian Transcriptional Repression
by Noncoding RNA. Institute of Science and Technology Austria, doi:10.15479/AT:ISTA:14644.
short: K. Tluckova, A.P. Testa Salmazo, C. Bernecky, (n.d.).
corr_author: '1'
date_created: 2023-12-04T14:51:00Z
date_published: 2023-12-05T00:00:00Z
date_updated: 2025-11-20T10:28:37Z
day: '05'
ddc:
- '572'
doi: 10.15479/AT:ISTA:14644
file:
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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
fulldoi: https://doi.org/10.15479/AT:ISTA:14644
has_accepted_license: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc/4.0/
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: draft
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '18778'
relation: later_version
status: public
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'
...
---
OA_place: publisher
OA_type: hybrid
_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 (in subscription journal)
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
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last_name: Broichhagen
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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. Nature Methods. 2023;20:1256-1265. doi:10.1038/s41592-023-01936-6
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. Nature Methods. Springer Nature. https://doi.org/10.1038/s41592-023-01936-6
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.” Nature Methods. Springer Nature, 2023. https://doi.org/10.1038/s41592-023-01936-6.
ieee: P. Velicky et al., “Dense 4D nanoscale reconstruction of living brain
tissue,” Nature Methods, 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.” Nature Methods, vol. 20, Springer Nature, 2023, pp. 1256–65, doi:10.1038/s41592-023-01936-6.
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.
corr_author: '1'
date_created: 2023-07-23T22:01:13Z
date_published: 2023-08-01T00:00:00Z
date_updated: 2026-07-06T12:49:46Z
day: '01'
ddc:
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doi: 10.1038/s41592-023-01936-6
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scopus_import: '1'
status: public
title: Dense 4D nanoscale reconstruction of living brain tissue
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)
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type: journal_article
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...
---
OA_place: publisher
_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:10.15479/at:ista:12809'
apa: 'Alcarva, C. (2023). Plasticity in the cerebellum: What molecular mechanisms
are behind physiological learning. Institute of Science and Technology Austria.
https://doi.org/10.15479/at:ista:12809'
chicago: 'Alcarva, Catarina. “Plasticity in the Cerebellum: What Molecular Mechanisms
Are behind Physiological Learning.” Institute of Science and Technology Austria,
2023. https://doi.org/10.15479/at:ista:12809.'
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. Plasticity in the Cerebellum: What Molecular Mechanisms
Are behind Physiological Learning. Institute of Science and Technology Austria,
2023, doi:10.15479/at:ista:12809.'
short: 'C. Alcarva, Plasticity in the Cerebellum: What Molecular Mechanisms Are
behind Physiological Learning, Institute of Science and Technology Austria, 2023.'
corr_author: '1'
date_created: 2023-04-06T07:54:09Z
date_published: 2023-04-06T00:00:00Z
date_updated: 2026-04-07T13:53:28Z
day: '06'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: RySh
doi: 10.15479/at:ista:12809
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publication_identifier:
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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: ba8df636-2132-11f1-aed0-ed93e2281fdd
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...