---
OA_place: repository
OA_type: green
_id: '21135'
abstract:
- lang: eng
  text: Three-dimensional (3D) microscopy data is often anisotropic with significantly
    lower resolution (up to 8x) along the z axis than along the xy axes. Computationally
    generating plausible isotropic resolution from anisotropic imaging data would
    benefit the visual analysis of large-scale volumes. This paper proposes niiv,
    a self-supervised method for isotropic reconstruction of 3D microscopy data that
    can quickly produce images at arbitrary output resolutions. The representation
    embeds a learned latent code within a neural field that describes the implicit
    higher-resolution isotropic image region. We use an attention-guided latent interpolation
    approach, which allows flexible information exchange over a local latent neighborhood.
    Under isotropic volume assumptions, we self-supervise this representation on low-/high-resolution
    lateral image pairs to reconstruct an isotropic volume from low-resolution axial
    images. We evaluate our method on simulated and real anisotropic electron (EM)
    and light microscopy (LM) data. Compared to diffusion-based baselines, niiv shows
    improved reconstruction quality (+1 dB PSNR) and is over three orders of magnitude
    faster (1,000x) to infer. Specifically, niiv reconstructs a 128^3 voxel volume
    in 2/10th of a second, renderable at varying (continuous) high resolutions for
    display. Our code is available at https://github.com/jakobtroidl/niiv-miccai.
acknowledgement: This work was supported by NIH grants 1U01NS132158 and R01HD104969.
  We thank the reviewers for their constructive feedback.
alternative_title:
- LNCS
article_processing_charge: No
author:
- first_name: Jakob
  full_name: Troidl, Jakob
  last_name: Troidl
- first_name: Yiqing
  full_name: Liang, Yiqing
  last_name: Liang
- first_name: Johanna
  full_name: Beyer, Johanna
  last_name: Beyer
- 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: Markus
  full_name: Hadwiger, Markus
  last_name: Hadwiger
- first_name: Hanspeter
  full_name: Pfister, Hanspeter
  last_name: Pfister
- first_name: James
  full_name: Tompkin, James
  last_name: Tompkin
citation:
  ama: 'Troidl J, Liang Y, Beyer J, et al. niiv: Interactive Self-supervised Neural
    Implicit Isotropic Volume Reconstruction. In: <i>1st International Workshop on
    Efficient Medical Artificial Intelligence</i>. Vol 16318. Springer Nature; 2026:257-267.
    doi:<a href="https://doi.org/10.1007/978-3-032-13961-0_26">10.1007/978-3-032-13961-0_26</a>'
  apa: 'Troidl, J., Liang, Y., Beyer, J., Tavakoli, M., Danzl, J. G., Hadwiger, M.,
    … Tompkin, J. (2026). niiv: Interactive Self-supervised Neural Implicit Isotropic
    Volume Reconstruction. In <i>1st International Workshop on Efficient Medical Artificial
    Intelligence</i> (Vol. 16318, pp. 257–267). Daejeon, South Korea: Springer Nature.
    <a href="https://doi.org/10.1007/978-3-032-13961-0_26">https://doi.org/10.1007/978-3-032-13961-0_26</a>'
  chicago: 'Troidl, Jakob, Yiqing Liang, Johanna Beyer, Mojtaba Tavakoli, Johann G
    Danzl, Markus Hadwiger, Hanspeter Pfister, and James Tompkin. “Niiv: Interactive
    Self-Supervised Neural Implicit Isotropic Volume Reconstruction.” In <i>1st International
    Workshop on Efficient Medical Artificial Intelligence</i>, 16318:257–67. Springer
    Nature, 2026. <a href="https://doi.org/10.1007/978-3-032-13961-0_26">https://doi.org/10.1007/978-3-032-13961-0_26</a>.'
  ieee: 'J. Troidl <i>et al.</i>, “niiv: Interactive Self-supervised Neural Implicit
    Isotropic Volume Reconstruction,” in <i>1st International Workshop on Efficient
    Medical Artificial Intelligence</i>, Daejeon, South Korea, 2026, vol. 16318, pp.
    257–267.'
  ista: 'Troidl J, Liang Y, Beyer J, Tavakoli M, Danzl JG, Hadwiger M, Pfister H,
    Tompkin J. 2026. niiv: Interactive Self-supervised Neural Implicit Isotropic Volume
    Reconstruction. 1st International Workshop on Efficient Medical Artificial Intelligence.
    EMA4MICCAI: Efficient Medical Artificial Intelligence, LNCS, vol. 16318, 257–267.'
  mla: 'Troidl, Jakob, et al. “Niiv: Interactive Self-Supervised Neural Implicit Isotropic
    Volume Reconstruction.” <i>1st International Workshop on Efficient Medical Artificial
    Intelligence</i>, vol. 16318, Springer Nature, 2026, pp. 257–67, doi:<a href="https://doi.org/10.1007/978-3-032-13961-0_26">10.1007/978-3-032-13961-0_26</a>.'
  short: J. Troidl, Y. Liang, J. Beyer, M. Tavakoli, J.G. Danzl, M. Hadwiger, H. Pfister,
    J. Tompkin, in:, 1st International Workshop on Efficient Medical Artificial Intelligence,
    Springer Nature, 2026, pp. 257–267.
conference:
  end_date: 2025-09-23
  location: Daejeon, South Korea
  name: 'EMA4MICCAI: Efficient Medical Artificial Intelligence'
  start_date: 2025-09-23
date_created: 2026-02-01T23:01:44Z
date_published: 2026-01-03T00:00:00Z
date_updated: 2026-02-16T08:50:50Z
day: '03'
department:
- _id: JoDa
doi: 10.1007/978-3-032-13961-0_26
intvolume: '     16318'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2024.09.07.611785
month: '01'
oa: 1
oa_version: Preprint
page: 257-267
publication: 1st International Workshop on Efficient Medical Artificial Intelligence
publication_identifier:
  eissn:
  - 1611-3349
  isbn:
  - '9783032139603'
  issn:
  - 0302-9743
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - relation: software
    url: https://github.com/jakobtroidl/niiv-miccai
scopus_import: '1'
status: public
title: 'niiv: Interactive Self-supervised Neural Implicit Isotropic Volume Reconstruction'
type: conference
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 16318
year: '2026'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '19003'
abstract:
- lang: eng
  text: 'Super-resolution methods provide far better spatial resolution than the optical
    diffraction limit of about half the wavelength of light (∼200-300 nm). Nevertheless,
    they have yet to attain widespread use in plants, largely due to plants’ challenging
    optical properties. Expansion microscopy improves effective resolution by isotropically
    increasing the physical distances between sample structures while preserving relative
    spatial arrangements and clearing the sample. However, its application to plants
    has been hindered by the rigid, mechanically cohesive structure of plant tissues.
    Here, we report on whole-mount expansion microscopy of thale cress (Arabidopsis
    thaliana) root tissues (PlantEx), achieving a four-fold resolution increase over
    conventional microscopy. Our results highlight the microtubule cytoskeleton organization
    and interaction between molecularly defined cellular constituents. Combining PlantEx
    with stimulated emission depletion (STED) microscopy, we increase nanoscale resolution
    and visualize the complex organization of subcellular organelles from intact tissues
    by example of the densely packed COPI-coated vesicles associated with the Golgi
    apparatus and put these into a cellular structural context. Our results show that
    expansion microscopy can be applied to increase effective imaging resolution in
    Arabidopsis root specimens. '
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: E-Lib
- _id: M-Shop
acknowledgement: "We gratefully acknowledge support by the Scientific Service Units
  at ISTA, including the Imaging and Optics and Lab Support facilities and the mechanical
  workshop and Library. We thank Philipp Velicky for STED microscope alignment.\r\nThis
  project has received funding from the European Research Council under the Horizon
  2020 Framework Programme (grant agreement No 742985, J.F.). It has also received
  funding from the Horizon 2020 Framework Programme under the Marie Skłodowska-Curie
  Grant Agreement No. 665385 (M.G.). S.T. has received funding as an ISTplus Fellow
  from the Horizon 2020 Framework Programme under Marie Skłodowska-Curie grant agreement
  no. 754411 and from EMBO via a Long-Term Fellowship (grant number ALTF 679-2018).
  M.R.T. received funding from the Austrian Academy of Sciences with DOC fellowship
  no. 26137. The project has further received funding from the Austrian Science Fund,
  via grant DK W1232 (M.R.T., N.A.D., and J.G.D). W.J. received a postdoctoral fellowship
  from the Human Frontier Science Program (LT000557/2018). The funders had no role
  in study design, data collection and analysis, decision to publish or preparation
  of the manuscript."
article_number: koaf006
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Michelle C
  full_name: Gallei, Michelle C
  id: 35A03822-F248-11E8-B48F-1D18A9856A87
  last_name: Gallei
  orcid: 0000-0003-1286-7368
- first_name: Sven M
  full_name: Truckenbrodt, Sven M
  id: 45812BD4-F248-11E8-B48F-1D18A9856A87
  last_name: Truckenbrodt
- first_name: Caroline
  full_name: Kreuzinger, Caroline
  id: 382077BA-F248-11E8-B48F-1D18A9856A87
  last_name: Kreuzinger
- first_name: Syamala
  full_name: Inumella, Syamala
  id: F8660870-D756-11E9-98C5-34DFE5697425
  last_name: Inumella
  orcid: 0009-0002-5890-120X
- first_name: Vitali
  full_name: Vistunou, Vitali
  id: 7e146587-8972-11ed-ae7b-d7a32ea86a81
  last_name: Vistunou
- 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: Mojtaba
  full_name: Tavakoli, Mojtaba
  id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
  last_name: Tavakoli
  orcid: 0000-0002-7667-6854
- first_name: Nathalie
  full_name: Agudelo Duenas, Nathalie
  id: 40E7F008-F248-11E8-B48F-1D18A9856A87
  last_name: Agudelo Duenas
- first_name: Jakob
  full_name: Vorlaufer, Jakob
  id: 937696FA-C996-11E9-8C7C-CF13E6697425
  last_name: Vorlaufer
  orcid: 0009-0000-7590-3501
- first_name: Wiebke
  full_name: Jahr, Wiebke
  id: 425C1CE8-F248-11E8-B48F-1D18A9856A87
  last_name: Jahr
- first_name: Marek
  full_name: Randuch, Marek
  id: 6ac4636d-15b2-11ec-abd3-fb8df79972ae
  last_name: Randuch
- first_name: Alexander J
  full_name: Johnson, Alexander J
  id: 46A62C3A-F248-11E8-B48F-1D18A9856A87
  last_name: Johnson
  orcid: 0000-0002-2739-8843
- first_name: Eva
  full_name: Benková, Eva
  id: 38F4F166-F248-11E8-B48F-1D18A9856A87
  last_name: Benková
  orcid: 0000-0002-8510-9739
- first_name: Jiří
  full_name: Friml, Jiří
  id: 4159519E-F248-11E8-B48F-1D18A9856A87
  last_name: Friml
  orcid: 0000-0002-8302-7596
- 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: Gallei MC, Truckenbrodt SM, Kreuzinger C, et al. Super-resolution expansion
    microscopy in plant roots. <i>The Plant Cell</i>. 2025;37(4). doi:<a href="https://doi.org/10.1093/plcell/koaf006">10.1093/plcell/koaf006</a>
  apa: Gallei, M. C., Truckenbrodt, S. M., Kreuzinger, C., Inumella, S., Vistunou,
    V., Sommer, C. M., … Danzl, J. G. (2025). Super-resolution expansion microscopy
    in plant roots. <i>The Plant Cell</i>. Oxford University Press. <a href="https://doi.org/10.1093/plcell/koaf006">https://doi.org/10.1093/plcell/koaf006</a>
  chicago: Gallei, Michelle C, Sven M Truckenbrodt, Caroline Kreuzinger, Syamala Inumella,
    Vitali Vistunou, Christoph M Sommer, Mojtaba Tavakoli, et al. “Super-Resolution
    Expansion Microscopy in Plant Roots.” <i>The Plant Cell</i>. Oxford University
    Press, 2025. <a href="https://doi.org/10.1093/plcell/koaf006">https://doi.org/10.1093/plcell/koaf006</a>.
  ieee: M. C. Gallei <i>et al.</i>, “Super-resolution expansion microscopy in plant
    roots,” <i>The Plant Cell</i>, vol. 37, no. 4. Oxford University Press, 2025.
  ista: Gallei MC, Truckenbrodt SM, Kreuzinger C, Inumella S, Vistunou V, Sommer CM,
    Tavakoli M, Agudelo Duenas N, Vorlaufer J, Jahr W, Randuch M, Johnson AJ, Benková
    E, Friml J, Danzl JG. 2025. Super-resolution expansion microscopy in plant roots.
    The Plant Cell. 37(4), koaf006.
  mla: Gallei, Michelle C., et al. “Super-Resolution Expansion Microscopy in Plant
    Roots.” <i>The Plant Cell</i>, vol. 37, no. 4, koaf006, Oxford University Press,
    2025, doi:<a href="https://doi.org/10.1093/plcell/koaf006">10.1093/plcell/koaf006</a>.
  short: M.C. Gallei, S.M. Truckenbrodt, C. Kreuzinger, S. Inumella, V. Vistunou,
    C.M. Sommer, M. Tavakoli, N. Agudelo Duenas, J. Vorlaufer, W. Jahr, M. Randuch,
    A.J. Johnson, E. Benková, J. Friml, J.G. Danzl, The Plant Cell 37 (2025).
corr_author: '1'
date_created: 2025-02-05T06:52:06Z
date_published: 2025-04-01T00:00:00Z
date_updated: 2025-10-08T08:43:56Z
day: '01'
ddc:
- '580'
department:
- _id: EvBe
- _id: JoDa
- _id: JiFr
doi: 10.1093/plcell/koaf006
ec_funded: 1
external_id:
  isi:
  - '001462763100001'
  pmid:
  - '39792900'
file:
- access_level: open_access
  checksum: 9d3f8218ff37a29f29c48a7bbe831bd3
  content_type: application/pdf
  creator: dernst
  date_created: 2025-07-31T07:03:43Z
  date_updated: 2025-07-31T07:03:43Z
  file_id: '20092'
  file_name: 2025_PlantCell_Gallei.pdf
  file_size: 53904111
  relation: main_file
  success: 1
file_date_updated: 2025-07-31T07:03:43Z
has_accepted_license: '1'
intvolume: '        37'
isi: 1
issue: '4'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 261099A6-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '742985'
  name: Tracing Evolution of Auxin Transport and Polarity in Plants
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
- _id: 269B5B22-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 679-2018
  name: UltraX - achieving sub-nanometer resolution in light microscopy using iterative
    X10 microscopy in combination with nanobodies and STED
- _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: The Plant Cell
publication_identifier:
  eissn:
  - 1532-298X
  issn:
  - 1040-4651
publication_status: published
publisher: Oxford University Press
quality_controlled: '1'
related_material:
  record:
  - id: '18689'
    relation: earlier_version
    status: public
  - id: '18837'
    relation: research_data
    status: public
scopus_import: '1'
status: public
title: Super-resolution expansion microscopy in plant roots
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: 37
year: '2025'
...
---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '19795'
abstract:
- lang: eng
  text: Super-resolution microscopy often entails long acquisition times of minutes
    to hours. Since drifts during the acquisition adversely affect data quality, active
    sample stabilization is commonly used for some of these techniques to reach their
    full potential. Although drifts in the lateral plane can often be corrected after
    acquisition, this is not always possible or may come with drawbacks. Therefore,
    it is appealing to stabilize sample position in three dimensions (3D) during acquisition.
    Various schemes for active sample stabilization have been demonstrated previously,
    with some reaching sub-nanometer stability in 3D. Here, we present a scheme for
    active drift correction that delivers the nanometer-scale 3D stability demanded
    by state-of-the-art super-resolution techniques and is straightforward to implement
    compared to previous schemes capable of reaching this level of stabilization precision.
    Using a refined algorithm that can handle various types of reference structure,
    without sparse signal peaks being mandatory, we stabilized sample position to
    ∼1 nm in 3D using objective lenses both with high and low numerical aperture.
    Our implementation requires only the addition of a simple widefield imaging path
    and we provide an open-source control software with graphical user interface to
    facilitate easy adoption of the module. Finally, we demonstrate how this has the
    potential to enhance data collection for diffraction-limited and super-resolution
    imaging techniques using single-molecule localization microscopy and cryo-confocal
    imaging as showcases.
acknowledged_ssus:
- _id: M-Shop
- _id: EM-Fac
- _id: LifeSc
acknowledgement: 'We acknowledge expert support by ISTA’s scientific service units,
  including the Miba Machine Shop, the Electron Microscopy Facility, and the Lab Support
  Facility. This work has been made possible in part by CZI grant DAF2021-234754 and
  grant DOI: https://doi.org/10.37921/812628ebpcwg from the Chan Zuckerberg Initiative
  DAF, an advised fund of Silicon Valley Community Foundation (funder DOI: https://doi.org/10.13039/100014989)
  (F.K.M.S. and J.G.D.). We further gratefully acknowledge funding by the following
  sources: Austrian Science Fund (FWF) grant DK W1232 (M.R.T. and J.G.D.); Austrian
  Academy of Sciences DOC fellowship 26137 (M.R.T.); Marie Skłodowska-Curie Actions
  Fellowship GA no. 665385 under the EU Horizon 2020 program (J.L.); ISTA postdoctoral
  fellowship IST fellow (A.W.); and Human Frontier Science Program postdoctoral fellowship
  LT000557/2018 (W.J.).'
article_number: '100211'
article_processing_charge: Yes
article_type: original
author:
- first_name: Jakob
  full_name: Vorlaufer, Jakob
  id: 937696FA-C996-11E9-8C7C-CF13E6697425
  last_name: Vorlaufer
  orcid: 0009-0000-7590-3501
- first_name: Nikolai
  full_name: Semenov, Nikolai
  id: e64d39c7-72ef-11ef-b75a-ee3046860d1b
  last_name: Semenov
- first_name: Caroline
  full_name: Kreuzinger, Caroline
  id: 382077BA-F248-11E8-B48F-1D18A9856A87
  last_name: Kreuzinger
- first_name: Manjunath
  full_name: Javoor, Manjunath
  id: 305ab18b-dc7d-11ea-9b2f-b58195228ea2
  last_name: Javoor
  orcid: 0000-0003-2311-2112
- first_name: Bettina
  full_name: Zens, Bettina
  id: 45FD126C-F248-11E8-B48F-1D18A9856A87
  last_name: Zens
  orcid: 0000-0002-9561-1239
- first_name: Nathalie
  full_name: Agudelo Duenas, Nathalie
  id: 40E7F008-F248-11E8-B48F-1D18A9856A87
  last_name: Agudelo Duenas
- first_name: Mojtaba
  full_name: Tavakoli, Mojtaba
  id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
  last_name: Tavakoli
  orcid: 0000-0002-7667-6854
- first_name: Marek
  full_name: Suplata, Marek
  id: EE8452B8-C26A-11E9-B157-E80CE6697425
  last_name: Suplata
- first_name: Wiebke
  full_name: Jahr, Wiebke
  id: 425C1CE8-F248-11E8-B48F-1D18A9856A87
  last_name: Jahr
  orcid: 0000-0003-0201-2315
- first_name: Julia
  full_name: Lyudchik, Julia
  id: 46E28B80-F248-11E8-B48F-1D18A9856A87
  last_name: Lyudchik
- first_name: Andreas
  full_name: Wartak, Andreas
  id: 60aaa06c-3de5-11eb-9e53-baa88e955dcb
  last_name: Wartak
- first_name: Florian Km
  full_name: Schur, Florian Km
  id: 48AD8942-F248-11E8-B48F-1D18A9856A87
  last_name: Schur
  orcid: 0000-0003-4790-8078
- 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: Vorlaufer J, Semenov N, Kreuzinger C, et al. Image-based 3D active sample stabilization
    on the nanometer scale for optical microscopy. <i>Biophysical Reports</i>. 2025;5(2).
    doi:<a href="https://doi.org/10.1016/j.bpr.2025.100211">10.1016/j.bpr.2025.100211</a>
  apa: Vorlaufer, J., Semenov, N., Kreuzinger, C., Javoor, M., Zens, B., Agudelo Duenas,
    N., … Danzl, J. G. (2025). Image-based 3D active sample stabilization on the nanometer
    scale for optical microscopy. <i>Biophysical Reports</i>. Elsevier. <a href="https://doi.org/10.1016/j.bpr.2025.100211">https://doi.org/10.1016/j.bpr.2025.100211</a>
  chicago: Vorlaufer, Jakob, Nikolai Semenov, Caroline Kreuzinger, Manjunath Javoor,
    Bettina Zens, Nathalie Agudelo Duenas, Mojtaba Tavakoli, et al. “Image-Based 3D
    Active Sample Stabilization on the Nanometer Scale for Optical Microscopy.” <i>Biophysical
    Reports</i>. Elsevier, 2025. <a href="https://doi.org/10.1016/j.bpr.2025.100211">https://doi.org/10.1016/j.bpr.2025.100211</a>.
  ieee: J. Vorlaufer <i>et al.</i>, “Image-based 3D active sample stabilization on
    the nanometer scale for optical microscopy,” <i>Biophysical Reports</i>, vol.
    5, no. 2. Elsevier, 2025.
  ista: Vorlaufer J, Semenov N, Kreuzinger C, Javoor M, Zens B, Agudelo Duenas N,
    Tavakoli M, Suplata M, Jahr W, Lyudchik J, Wartak A, Schur FK, Danzl JG. 2025.
    Image-based 3D active sample stabilization on the nanometer scale for optical
    microscopy. Biophysical Reports. 5(2), 100211.
  mla: Vorlaufer, Jakob, et al. “Image-Based 3D Active Sample Stabilization on the
    Nanometer Scale for Optical Microscopy.” <i>Biophysical Reports</i>, vol. 5, no.
    2, 100211, Elsevier, 2025, doi:<a href="https://doi.org/10.1016/j.bpr.2025.100211">10.1016/j.bpr.2025.100211</a>.
  short: J. Vorlaufer, N. Semenov, C. Kreuzinger, M. Javoor, B. Zens, N. Agudelo Duenas,
    M. Tavakoli, M. Suplata, W. Jahr, J. Lyudchik, A. Wartak, F.K. Schur, J.G. Danzl,
    Biophysical Reports 5 (2025).
corr_author: '1'
date_created: 2025-06-08T22:01:22Z
date_published: 2025-06-11T00:00:00Z
date_updated: 2026-04-07T11:48:07Z
day: '11'
ddc:
- '570'
department:
- _id: JoDa
- _id: GradSch
- _id: FlSc
- _id: EM-Fac
doi: 10.1016/j.bpr.2025.100211
ec_funded: 1
file:
- access_level: open_access
  checksum: 4018c833f25a3ad3b57e3577fed70334
  content_type: application/pdf
  creator: dernst
  date_created: 2025-06-10T07:24:46Z
  date_updated: 2025-06-10T07:24:46Z
  file_id: '19802'
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  file_size: 7238179
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  success: 1
file_date_updated: 2025-06-10T07:24:46Z
has_accepted_license: '1'
intvolume: '         5'
issue: '2'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
project:
- _id: 62909c6f-2b32-11ec-9570-e1476aab5308
  grant_number: CZI01
  name: CryoMinflux-guided in-situ molecular census and structure determination
- _id: 6285a163-2b32-11ec-9570-8e204ca2dba5
  grant_number: '26137'
  name: Studying Organelle Structure and Function at Nanoscale Resolution with Expansion
    Microscopy
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 26AA4EF2-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232-B24
  name: Molecular Drug Targets
- _id: 2668BFA0-B435-11E9-9278-68D0E5697425
  grant_number: LT00057
  name: High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration
publication: Biophysical Reports
publication_identifier:
  eissn:
  - 2667-0747
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  record:
  - id: '20206'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Image-based 3D active sample stabilization on the nanometer scale for optical
  microscopy
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 5
year: '2025'
...
---
OA_place: publisher
OA_type: hybrid
_id: '18879'
abstract:
- lang: eng
  text: 'Our brain has remarkable computational power, generating sophisticated behaviors,
    storing memories over an individual’s lifetime, and producing higher cognitive
    functions. However, little of our neuroscience knowledge covers the human brain.
    Is this organ truly unique, or is it a scaled version of the extensively studied
    rodent brain? Combining multicellular patch-clamp recording with expansion-based
    superresolution microscopy and full-scale modeling, we determined the cellular
    and microcircuit properties of the human hippocampal CA3 region, a fundamental
    circuit for memory storage. In contrast to neocortical networks, human hippocampal
    CA3 displayed sparse connectivity, providing a circuit architecture that maximizes
    associational power. Human synapses showed unique reliability, high precision,
    and long integration times, exhibiting both species- and circuit-specific properties.
    Together with expanded neuronal numbers, these circuit characteristics greatly
    enhanced the memory storage capacity of CA3. Our results reveal distinct microcircuit
    properties of the human hippocampus and begin to unravel the inner workings of
    our most complex organ. '
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
- _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, Walter Kaufmann
  for assistance with handling frozen tissue, and Eleftheria Kralli-Beller for manuscript
  editing. This research was supported by the Scientific Services Units (SSUs) of
  ISTA, and we are grateful for assistance from Christoph Sommer and the Imaging and
  Optics Facility, Preclinical Facility, Lab Support Facility, Miba Machine Shop,
  and Scientific Computing. We are particularly grateful to the patient donors for
  their support of this project and also acknowledge the excellent support of the
  Medical University of Vienna Department of Neurosurgery staff; Romana Hoeftberger
  and the Division of Neuropathology and Neurochemistry; Gregor Kasprian and the Division
  of Neuroradiology and Musculoskeletal Radiology; and Christoph Baumgartner, Martha
  Feucht, and Ekaterina Pataraia for their clinical care of the patients included
  in this study. We thank Laura Jonkman, the NABCA biobank, and postmortem brain sample
  donors for their support of this research. The project received funding from the
  European Research Council (ERC) under the European Union’s Horizon 2020 research
  and innovation programme (advanced grant no. 692692 to P.J. and Marie Skłodowska-Curie
  Actions Individual Fellowship no. 101026635 to J.F.W.), the Austrian Science Fund
  (FWF; grant PAT 4178023 to P.J. and grant DK W1232 to M.R.T. and J.G.D.), the Austrian
  Academy of Sciences (DOC fellowship 26137 to M.R.T.), and a NOMIS-ISTA fellowship
  (to A.N.-O.).
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Jake
  full_name: Watson, Jake
  id: 63836096-4690-11EA-BD4E-32803DDC885E
  last_name: Watson
  orcid: 0000-0002-8698-3823
- first_name: Victor M
  full_name: Vargas Barroso, Victor M
  id: 2F55A9DE-F248-11E8-B48F-1D18A9856A87
  last_name: Vargas Barroso
- first_name: Rebecca
  full_name: Morse, Rebecca
  id: ceb89ae7-dc8d-11ea-abe3-da3301d0eab4
  last_name: Morse
- first_name: Andrea C
  full_name: Navas Olivé, Andrea C
  id: 739d26c9-52e8-11ee-8d72-f14d3893b4ce
  last_name: Navas Olivé
  orcid: 0000-0002-9280-8597
- 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 J, Vargas Barroso VM, Morse R, et al. Human hippocampal CA3 uses specific
    functional connectivity rules for efficient associative memory. <i>Cell</i>. 2025;188(2):501-514.e18.
    doi:<a href="https://doi.org/10.1016/j.cell.2024.11.022">10.1016/j.cell.2024.11.022</a>
  apa: Watson, J., Vargas Barroso, V. M., Morse, R., Navas Olivé, A. C., Tavakoli,
    M., Danzl, J. G., … Jonas, P. M. (2025). Human hippocampal CA3 uses specific functional
    connectivity rules for efficient associative memory. <i>Cell</i>. Elsevier. <a
    href="https://doi.org/10.1016/j.cell.2024.11.022">https://doi.org/10.1016/j.cell.2024.11.022</a>
  chicago: Watson, Jake, Victor M Vargas Barroso, Rebecca Morse, Andrea C Navas Olivé,
    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.” <i>Cell</i>. Elsevier, 2025. <a href="https://doi.org/10.1016/j.cell.2024.11.022">https://doi.org/10.1016/j.cell.2024.11.022</a>.
  ieee: J. Watson <i>et al.</i>, “Human hippocampal CA3 uses specific functional connectivity
    rules for efficient associative memory,” <i>Cell</i>, vol. 188, no. 2. Elsevier,
    p. 501–514.e18, 2025.
  ista: Watson J, Vargas Barroso VM, Morse R, Navas Olivé AC, Tavakoli M, Danzl JG,
    Tomschik M, Rössler K, Jonas PM. 2025. Human hippocampal CA3 uses specific functional
    connectivity rules for efficient associative memory. Cell. 188(2), 501–514.e18.
  mla: Watson, Jake, et al. “Human Hippocampal CA3 Uses Specific Functional Connectivity
    Rules for Efficient Associative Memory.” <i>Cell</i>, vol. 188, no. 2, Elsevier,
    2025, p. 501–514.e18, doi:<a href="https://doi.org/10.1016/j.cell.2024.11.022">10.1016/j.cell.2024.11.022</a>.
  short: J. Watson, V.M. Vargas Barroso, R. Morse, A.C. Navas Olivé, M. Tavakoli,
    J.G. Danzl, M. Tomschik, K. Rössler, P.M. Jonas, Cell 188 (2025) 501–514.e18.
corr_author: '1'
date_created: 2025-01-26T23:01:49Z
date_published: 2025-01-23T00:00:00Z
date_updated: 2026-04-14T08:34:32Z
day: '23'
ddc:
- '570'
department:
- _id: JoDa
- _id: PeJo
- _id: GradSch
doi: 10.1016/j.cell.2024.11.022
ec_funded: 1
external_id:
  isi:
  - '001408395600001'
  pmid:
  - '39667938'
file:
- access_level: open_access
  checksum: d5a818edc32d249cdf75e1bb5b70a4b7
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  creator: dernst
  date_created: 2025-01-27T08:46:33Z
  date_updated: 2025-01-27T08:46:33Z
  file_id: '18884'
  file_name: 2025_Cell_Watson.pdf
  file_size: 14082343
  relation: main_file
  success: 1
file_date_updated: 2025-01-27T08:46:33Z
has_accepted_license: '1'
intvolume: '       188'
isi: 1
issue: '2'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: 501-514.e18
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: fc2be41b-9c52-11eb-aca3-faa90aa144e9
  call_identifier: H2020
  grant_number: '101026635'
  name: Synaptic computations of the hippocampal CA3 circuitry
- _id: 6285a163-2b32-11ec-9570-8e204ca2dba5
  grant_number: '26137'
  name: Studying Organelle Structure and Function at Nanoscale Resolution with Expansion
    Microscopy
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232
  name: Molecular Drug Targets
- _id: 8d9195e9-16d5-11f0-9cad-d075be887a1e
  grant_number: PAT 4178023
  name: Synaptic networks of human brain
- _id: 9B861AAC-BA93-11EA-9121-9846C619BF3A
  name: NOMIS Fellowship Program
publication: Cell
publication_identifier:
  eissn:
  - 1097-4172
  issn:
  - 0092-8674
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  record:
  - id: '18688'
    relation: earlier_version
    status: public
scopus_import: '1'
status: public
title: Human hippocampal CA3 uses specific functional connectivity rules for efficient
  associative memory
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: 188
year: '2025'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '19704'
abstract:
- lang: eng
  text: The information-processing capability of the brain’s cellular network depends
    on the physical wiring pattern between neurons and their molecular and functional
    characteristics. Mapping neurons and resolving their individual synaptic connections
    can be achieved by volumetric imaging at nanoscale resolution1,2 with dense cellular
    labelling. Light microscopy is uniquely positioned to visualize specific molecules,
    but dense, synapse-level circuit reconstruction by light microscopy has been out
    of reach, owing to limitations in resolution, contrast and volumetric imaging
    capability. Here we describe light-microscopy-based connectomics (LICONN). We
    integrated specifically engineered hydrogel embedding and expansion with comprehensive
    deep-learning-based segmentation and analysis of connectivity, thereby directly
    incorporating molecular information into synapse-level reconstructions of brain
    tissue. LICONN will allow synapse-level phenotyping of brain tissue in biological
    experiments in a readily adoptable manner.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: ScienComp
- _id: PreCl
- _id: M-Shop
- _id: E-Lib
acknowledgement: 'We thank S. Dorkenwald and P. Li for critical reading of the manuscript,
  S. Loomba for discussions and E. Miguel for support with data handling. We acknowledge
  support from ISTA’s scientific service units: Imaging and Optics, Lab Support, Scientific
  Computing, the preclinical facility, the Miba Machine Shop and the library. We acknowledge
  funding from the following sources: Austrian Science Fund (FWF) grant DK W1232 (J.G.D.
  and M.R.T.); Austrian Academy of Sciences DOC fellowship 26137 (M.R.T.); Gesellschaft
  für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.); the European Union’s
  Horizon 2020 research and innovation programme and Marie Skłodowska-Curie Actions
  Fellowship 665385 (J.L.); and the European Union’s Horizon 2020 research and innovation
  programme and European Research Council (ERC) grant 101044865 ‘SecretAutism’ (G.N.).Open
  access funding provided by Institute of Science and Technology (IST Austria).'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Mojtaba
  full_name: Tavakoli, Mojtaba
  id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
  last_name: Tavakoli
  orcid: 0000-0002-7667-6854
- first_name: Julia
  full_name: Lyudchik, Julia
  id: 46E28B80-F248-11E8-B48F-1D18A9856A87
  last_name: Lyudchik
- first_name: Michał
  full_name: Januszewski, Michał
  last_name: Januszewski
- first_name: Vitali
  full_name: Vistunou, Vitali
  id: 7e146587-8972-11ed-ae7b-d7a32ea86a81
  last_name: Vistunou
- first_name: Nathalie
  full_name: Agudelo Duenas, Nathalie
  id: 40E7F008-F248-11E8-B48F-1D18A9856A87
  last_name: Agudelo Duenas
- first_name: Jakob
  full_name: Vorlaufer, Jakob
  id: 937696FA-C996-11E9-8C7C-CF13E6697425
  last_name: Vorlaufer
  orcid: 0009-0000-7590-3501
- 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: Caroline
  full_name: Kreuzinger, Caroline
  id: 382077BA-F248-11E8-B48F-1D18A9856A87
  last_name: Kreuzinger
- first_name: Bárbara
  full_name: Oliveira, Bárbara
  id: 3B03AA1A-F248-11E8-B48F-1D18A9856A87
  last_name: Oliveira
- first_name: Alban
  full_name: Cenameri, Alban
  id: 9ac8f577-2357-11eb-997a-e566c5550886
  last_name: Cenameri
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Viren
  full_name: Jain, Viren
  last_name: Jain
- 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: Tavakoli M, Lyudchik J, Januszewski M, et al. Light-microscopy-based connectomic
    reconstruction of mammalian brain tissue. <i>Nature</i>. 2025;642:398-410. doi:<a
    href="https://doi.org/10.1038/s41586-025-08985-1">10.1038/s41586-025-08985-1</a>
  apa: Tavakoli, M., Lyudchik, J., Januszewski, M., Vistunou, V., Agudelo Duenas,
    N., Vorlaufer, J., … Danzl, J. G. (2025). Light-microscopy-based connectomic reconstruction
    of mammalian brain tissue. <i>Nature</i>. Springer Nature. <a href="https://doi.org/10.1038/s41586-025-08985-1">https://doi.org/10.1038/s41586-025-08985-1</a>
  chicago: Tavakoli, Mojtaba, Julia Lyudchik, Michał Januszewski, Vitali Vistunou,
    Nathalie Agudelo Duenas, Jakob Vorlaufer, Christoph M Sommer, et al. “Light-Microscopy-Based
    Connectomic Reconstruction of Mammalian Brain Tissue.” <i>Nature</i>. Springer
    Nature, 2025. <a href="https://doi.org/10.1038/s41586-025-08985-1">https://doi.org/10.1038/s41586-025-08985-1</a>.
  ieee: M. Tavakoli <i>et al.</i>, “Light-microscopy-based connectomic reconstruction
    of mammalian brain tissue,” <i>Nature</i>, vol. 642. Springer Nature, pp. 398–410,
    2025.
  ista: Tavakoli M, Lyudchik J, Januszewski M, Vistunou V, Agudelo Duenas N, Vorlaufer
    J, Sommer CM, Kreuzinger C, Oliveira B, Cenameri A, Novarino G, Jain V, Danzl
    JG. 2025. Light-microscopy-based connectomic reconstruction of mammalian brain
    tissue. Nature. 642, 398–410.
  mla: Tavakoli, Mojtaba, et al. “Light-Microscopy-Based Connectomic Reconstruction
    of Mammalian Brain Tissue.” <i>Nature</i>, vol. 642, Springer Nature, 2025, pp.
    398–410, doi:<a href="https://doi.org/10.1038/s41586-025-08985-1">10.1038/s41586-025-08985-1</a>.
  short: M. Tavakoli, J. Lyudchik, M. Januszewski, V. Vistunou, N. Agudelo Duenas,
    J. Vorlaufer, C.M. Sommer, C. Kreuzinger, B. Oliveira, A. Cenameri, G. Novarino,
    V. Jain, J.G. Danzl, Nature 642 (2025) 398–410.
corr_author: '1'
date_created: 2025-05-18T22:02:51Z
date_published: 2025-06-12T00:00:00Z
date_updated: 2026-04-28T13:33:34Z
day: '12'
ddc:
- '570'
department:
- _id: JoDa
- _id: GradSch
- _id: Bio
- _id: GaNo
doi: 10.1038/s41586-025-08985-1
ec_funded: 1
external_id:
  isi:
  - '001483477000001'
  pmid:
  - '40335689'
file:
- access_level: open_access
  checksum: ebc99d7108e728f46db0a009292675ef
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  creator: dernst
  date_created: 2025-07-03T06:55:20Z
  date_updated: 2025-07-03T06:55:20Z
  file_id: '19959'
  file_name: 2025_Nature_Tavakoli.pdf
  file_size: 133201290
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file_date_updated: 2025-07-03T06:55:20Z
has_accepted_license: '1'
intvolume: '       642'
isi: 1
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: 398-410
pmid: 1
project:
- _id: 6285a163-2b32-11ec-9570-8e204ca2dba5
  grant_number: '26137'
  name: Studying Organelle Structure and Function at Nanoscale Resolution with Expansion
    Microscopy
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 34ba8964-11ca-11ed-8bc3-e15864e7e9a6
  grant_number: '101044865'
  name: Toward an understanding of the brain interstitial system and the extracellular
    proteome in health and autism spectrum disorders
- _id: 26AA4EF2-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232-B24
  name: Molecular Drug Targets
publication: Nature
publication_identifier:
  eissn:
  - 1476-4687
  issn:
  - 0028-0836
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - description: News on ISTA website
    relation: press_release
    url: https://ista.ac.at/en/news/piecing-together-the-brain-puzzle/
  record:
  - id: '18677'
    relation: earlier_version
    status: public
  - id: '18697'
    relation: research_data
    status: public
scopus_import: '1'
status: public
title: Light-microscopy-based connectomic reconstruction of mammalian 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)
  short: CC BY (4.0)
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 642
year: '2025'
...
---
OA_place: repository
_id: '18689'
abstract:
- lang: eng
  text: Multiplexed fluorescence microscopy imaging is widely used in biomedical applications.
    However, simultaneous imaging of multiple fluorophores can result in spectral
    leaks and overlapping, which greatly degrades image quality and subsequent analysis.
    Existing popular spectral unmixing methods are mainly based on computational intensive
    linear models and the performance is heavily dependent on the reference spectra,
    which may greatly preclude its further applications. In this paper, we propose
    a deep learning-based blindly spectral unmixing method, termed AutoUnmix, to imitate
    the physical spectral mixing process. A tranfer learning framework is further
    devised to allow our AutoUnmix adapting to a variety of imaging systems without
    retraining the network. Our proposed method has demonstrated real-time unmixing
    capabilities, surpassing existing methods by up to 100-fold in terms of unmixing
    speed. We further validate the reconstruction performance on both synthetic datasets
    and biological samples. The unmixing results of AutoUnmix achieve a highest SSIM
    of 0.99 in both three- and four-color imaging, with nearly up to 20% higher than
    other popular unmixing methods. Due to the desirable property of data independency
    and superior blind unmixing performance, we believe AutoUnmix is a powerful tool
    to study the interaction process of different organelles labeled by multiple fluorophores.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: M-Shop
- _id: E-Lib
acknowledgement: "We gratefully acknowledge support by the Scientific Service Units
  at ISTA, including the Imaging and Optics and Lab Support facilities and the mechanical
  workshop and Library. We thank Philipp Velicky for STED microscope alignment.\r\n\r\nThis
  project has received funding from the Austrian Science Fund (FWF): I 3630-B25 (J.G.D)
  and the European Research Council (ERC) under the European Union’s Horizon 2020
  research and innovation programme (grant agreement No 742985, J.F.). It has also
  received funding from the European Union’s Horizon 2020 research and innovation
  programme under the Marie Skłodowska-Curie Grant Agreement No. 665385. S.T. has
  received funding as an ISTplus Fellow from the European Union’s Horizon 2020 Research
  and Innovation Programme under Marie Skłodowska-Curie grant agreement no. 754411
  and from an EMBO Long-Term Fellowship (grant number ALTF 679-2018). It has further
  received funding from the Austrian Science Fund (FWF) grant DK W1232 (M.T, N.A-D.,
  J.G.D). W.J. received funding via a Human Frontier Science Program postdoctoral
  fellowship LT000557/2018.\r\n\r\nThe funders had no role in study design, data collection
  and analysis, decision to publish or preparation of the manuscript."
article_processing_charge: No
author:
- first_name: Michelle C
  full_name: Gallei, Michelle C
  id: 35A03822-F248-11E8-B48F-1D18A9856A87
  last_name: Gallei
  orcid: 0000-0003-1286-7368
- first_name: Sven M
  full_name: Truckenbrodt, Sven M
  id: 45812BD4-F248-11E8-B48F-1D18A9856A87
  last_name: Truckenbrodt
- first_name: Caroline
  full_name: Kreuzinger, Caroline
  id: 382077BA-F248-11E8-B48F-1D18A9856A87
  last_name: Kreuzinger
- first_name: Syamala
  full_name: Inumella, Syamala
  id: F8660870-D756-11E9-98C5-34DFE5697425
  last_name: Inumella
  orcid: 0009-0002-5890-120X
- first_name: Vitali
  full_name: Vistunou, Vitali
  id: 7e146587-8972-11ed-ae7b-d7a32ea86a81
  last_name: Vistunou
- 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: Mojtaba
  full_name: Tavakoli, Mojtaba
  id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
  last_name: Tavakoli
  orcid: 0000-0002-7667-6854
- first_name: Nathalie
  full_name: Agudelo Duenas, Nathalie
  id: 40E7F008-F248-11E8-B48F-1D18A9856A87
  last_name: Agudelo Duenas
- first_name: Jakob
  full_name: Vorlaufer, Jakob
  id: 937696FA-C996-11E9-8C7C-CF13E6697425
  last_name: Vorlaufer
  orcid: 0009-0000-7590-3501
- first_name: Wiebke
  full_name: Jahr, Wiebke
  id: 425C1CE8-F248-11E8-B48F-1D18A9856A87
  last_name: Jahr
  orcid: 0000-0003-0201-2315
- first_name: Marek
  full_name: Randuch, Marek
  id: 6ac4636d-15b2-11ec-abd3-fb8df79972ae
  last_name: Randuch
- first_name: Alexander J
  full_name: Johnson, Alexander J
  id: 46A62C3A-F248-11E8-B48F-1D18A9856A87
  last_name: Johnson
  orcid: 0000-0002-2739-8843
- first_name: Eva
  full_name: Benková, Eva
  id: 38F4F166-F248-11E8-B48F-1D18A9856A87
  last_name: Benková
  orcid: 0000-0002-8510-9739
- first_name: Jiří
  full_name: Friml, Jiří
  id: 4159519E-F248-11E8-B48F-1D18A9856A87
  last_name: Friml
  orcid: 0000-0002-8302-7596
- 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: Gallei MC, Truckenbrodt SM, Kreuzinger C, et al. Super-resolution expansion
    microscopy in plant roots. <i>bioRxiv</i>. doi:<a href="https://doi.org/10.1101/2024.02.21.581330">10.1101/2024.02.21.581330</a>
  apa: Gallei, M. C., Truckenbrodt, S. M., Kreuzinger, C., Inumella, S., Vistunou,
    V., Sommer, C. M., … Danzl, J. G. (n.d.). Super-resolution expansion microscopy
    in plant roots. <i>bioRxiv</i>. <a href="https://doi.org/10.1101/2024.02.21.581330">https://doi.org/10.1101/2024.02.21.581330</a>
  chicago: Gallei, Michelle C, Sven M Truckenbrodt, Caroline Kreuzinger, Syamala Inumella,
    Vitali Vistunou, Christoph M Sommer, Mojtaba Tavakoli, et al. “Super-Resolution
    Expansion Microscopy in Plant Roots.” <i>BioRxiv</i>, n.d. <a href="https://doi.org/10.1101/2024.02.21.581330">https://doi.org/10.1101/2024.02.21.581330</a>.
  ieee: M. C. Gallei <i>et al.</i>, “Super-resolution expansion microscopy in plant
    roots,” <i>bioRxiv</i>. .
  ista: Gallei MC, Truckenbrodt SM, Kreuzinger C, Inumella S, Vistunou V, Sommer CM,
    Tavakoli M, Agudelo Duenas N, Vorlaufer J, Jahr W, Randuch M, Johnson AJ, Benková
    E, Friml J, Danzl JG. Super-resolution expansion microscopy in plant roots. bioRxiv,
    <a href="https://doi.org/10.1101/2024.02.21.581330">10.1101/2024.02.21.581330</a>.
  mla: Gallei, Michelle C., et al. “Super-Resolution Expansion Microscopy in Plant
    Roots.” <i>BioRxiv</i>, doi:<a href="https://doi.org/10.1101/2024.02.21.581330">10.1101/2024.02.21.581330</a>.
  short: M.C. Gallei, S.M. Truckenbrodt, C. Kreuzinger, S. Inumella, V. Vistunou,
    C.M. Sommer, M. Tavakoli, N. Agudelo Duenas, J. Vorlaufer, W. Jahr, M. Randuch,
    A.J. Johnson, E. Benková, J. Friml, J.G. Danzl, BioRxiv (n.d.).
corr_author: '1'
date_created: 2024-12-19T12:28:00Z
date_published: 2024-02-21T00:00:00Z
date_updated: 2026-04-07T12:56:36Z
day: '21'
department:
- _id: EvBe
- _id: JoDa
- _id: JiFr
doi: 10.1101/2024.02.21.581330
ec_funded: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2024.02.21.581330
month: '02'
oa: 1
oa_version: Preprint
project:
- _id: 261099A6-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '742985'
  name: Tracing Evolution of Auxin Transport and Polarity in Plants
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
- _id: 26AA4EF2-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232-B24
  name: Molecular Drug Targets
- _id: 269B5B22-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 679-2018
  name: UltraX - achieving sub-nanometer resolution in light microscopy using iterative
    X10 microscopy in combination with nanobodies and STED
publication: bioRxiv
publication_status: draft
related_material:
  record:
  - id: '19003'
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  - id: '18681'
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status: public
title: Super-resolution expansion microscopy in plant roots
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: '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:<a href="https://doi.org/10.15479/at:ista:18681">10.15479/at:ista:18681</a>'
  apa: 'Tavakoli, M. (2024). <i>Developing molecular and structural tools for studying
    brain architecture with super resolution expansion microscopy. LICONN: Molecularly-informed
    connectomics reconstruction with light microscopy</i>. Institute of Science and
    Technology Austria. <a href="https://doi.org/10.15479/at:ista:18681">https://doi.org/10.15479/at:ista:18681</a>'
  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. <a href="https://doi.org/10.15479/at:ista:18681">https://doi.org/10.15479/at:ista:18681</a>.'
  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. <i>Developing Molecular and Structural Tools for Studying
    Brain Architecture with Super Resolution Expansion Microscopy. LICONN: Molecularly-Informed
    Connectomics Reconstruction with Light Microscopy</i>. Institute of Science and
    Technology Austria, 2024, doi:<a href="https://doi.org/10.15479/at:ista:18681">10.15479/at:ista:18681</a>.'
  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'
date_created: 2024-12-19T02:30:39Z
date_published: 2024-12-20T00:00:00Z
date_updated: 2026-04-07T12:56:37Z
day: '20'
ddc:
- '600'
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: JoDa
doi: 10.15479/at:ista:18681
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  date_created: 2024-12-20T10:23:17Z
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has_accepted_license: '1'
language:
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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:
  - id: '11160'
    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: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
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. <i>bioRxiv</i>.
    doi:<a href="https://doi.org/10.1101/2024.05.02.592169">10.1101/2024.05.02.592169</a>
  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. <i>bioRxiv</i>. <a href="https://doi.org/10.1101/2024.05.02.592169">https://doi.org/10.1101/2024.05.02.592169</a>
  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.” <i>BioRxiv</i>, n.d. <a href="https://doi.org/10.1101/2024.05.02.592169">https://doi.org/10.1101/2024.05.02.592169</a>.
  ieee: J. F. Watson <i>et al.</i>, “Human hippocampal CA3 uses specific functional
    connectivity rules for efficient associative memory,” <i>bioRxiv</i>. .
  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, <a href="https://doi.org/10.1101/2024.05.02.592169">10.1101/2024.05.02.592169</a>.
  mla: Watson, Jake F., et al. “Human Hippocampal CA3 Uses Specific Functional Connectivity
    Rules for Efficient Associative Memory.” <i>BioRxiv</i>, doi:<a href="https://doi.org/10.1101/2024.05.02.592169">10.1101/2024.05.02.592169</a>.
  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: 2026-04-14T08:34:32Z
day: '02'
department:
- _id: JoDa
- _id: PeJo
doi: 10.1101/2024.05.02.592169
ec_funded: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2024.05.02.592169
month: '05'
oa: 1
oa_version: Preprint
project:
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
  call_identifier: H2020
  grant_number: '101026635'
  name: Synaptic computations of the hippocampal CA3 circuitry
- _id: 26AA4EF2-B435-11E9-9278-68D0E5697425
  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:
  record:
  - id: '18681'
    relation: dissertation_contains
    status: public
  - id: '18879'
    relation: later_version
    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_place: repository
_id: '18677'
abstract:
- lang: eng
  text: The information-processing capability of the brain’s cellular network depends
    on the physical wiring pattern between neurons and their molecular and functional
    characteristics. Mapping neurons and resolving their individual synaptic connections
    can be achieved by volumetric imaging at nanoscale resolution with dense cellular
    labeling. Light microscopy is uniquely positioned to visualize specific molecules
    but dense, synapse-level circuit reconstruction by light microscopy has been out
    of reach due to limitations in resolution, contrast, and volumetric imaging capability.
    Here we developed light-microscopy based connectomics (LICONN). We integrated
    specifically engineered hydrogel embedding and expansion with comprehensive deep-learning
    based segmentation and analysis of connectivity, thus directly incorporating molecular
    information in synapse-level brain tissue reconstructions. LICONN will allow synapse-level
    brain tissue phenotyping in biological experiments in a readily adoptable manner.
acknowledged_ssus:
- _id: E-Lib
- _id: M-Shop
- _id: LifeSc
- _id: Bio
- _id: ScienComp
acknowledgement: "We thank Sven Dorkenwald and Peter Li for critical reading of the\r\nmanuscript.
  We acknowledge expert support by ISTA’s scientific service units: Imaging and\r\nOptics,
  Lab Support, Scientific Computing, Preclinical Facility, Miba Machine Shop, and
  Library.\r\nWe gratefully acknowledge funding by the following sources:\r\nAustrian
  Science Fund (FWF) grant DK W1232 (JGD, MRT)\r\nAustrian Academy of Sciences DOC
  fellowship 26137 (MRT)\r\nEU Horizon 2020 program, Marie Skłodowska-Curie Actions
  Fellowship 665385 (JL)\r\nGesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022
  (JGD)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European
  Research\r\nCouncil (ERC) grant 101044865 “SecretAutism.”\r\n"
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
- first_name: Julia
  full_name: Lyudchik, Julia
  id: 46E28B80-F248-11E8-B48F-1D18A9856A87
  last_name: Lyudchik
- first_name: Michał
  full_name: Januszewski, Michał
  last_name: Januszewski
- first_name: Vitali
  full_name: Vistunou, Vitali
  id: 7e146587-8972-11ed-ae7b-d7a32ea86a81
  last_name: Vistunou
- first_name: Nathalie
  full_name: Agudelo Duenas, Nathalie
  id: 40E7F008-F248-11E8-B48F-1D18A9856A87
  last_name: Agudelo Duenas
- first_name: Jakob
  full_name: Vorlaufer, Jakob
  id: 937696FA-C996-11E9-8C7C-CF13E6697425
  last_name: Vorlaufer
  orcid: 0009-0000-7590-3501
- 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: Caroline
  full_name: Kreuzinger, Caroline
  id: 382077BA-F248-11E8-B48F-1D18A9856A87
  last_name: Kreuzinger
- first_name: Bárbara
  full_name: Oliveira, Bárbara
  id: 3B03AA1A-F248-11E8-B48F-1D18A9856A87
  last_name: Oliveira
- first_name: Alban
  full_name: Cenameri, Alban
  id: 9ac8f577-2357-11eb-997a-e566c5550886
  last_name: Cenameri
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Viren
  full_name: Jain, Viren
  last_name: Jain
- 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: Tavakoli M, Lyudchik J, Januszewski M, et al. Light-microscopy based dense
    connectomic reconstruction of mammalian brain tissue. <i>bioRxiv</i>. doi:<a href="https://doi.org/10.1101/2024.03.01.582884">10.1101/2024.03.01.582884</a>
  apa: Tavakoli, M., Lyudchik, J., Januszewski, M., Vistunou, V., Agudelo Duenas,
    N., Vorlaufer, J., … Danzl, J. G. (n.d.). Light-microscopy based dense connectomic
    reconstruction of mammalian brain tissue. <i>bioRxiv</i>. <a href="https://doi.org/10.1101/2024.03.01.582884">https://doi.org/10.1101/2024.03.01.582884</a>
  chicago: Tavakoli, Mojtaba, Julia Lyudchik, Michał Januszewski, Vitali Vistunou,
    Nathalie Agudelo Duenas, Jakob Vorlaufer, Christoph M Sommer, et al. “Light-Microscopy
    Based Dense Connectomic Reconstruction of Mammalian Brain Tissue.” <i>BioRxiv</i>,
    n.d. <a href="https://doi.org/10.1101/2024.03.01.582884">https://doi.org/10.1101/2024.03.01.582884</a>.
  ieee: M. Tavakoli <i>et al.</i>, “Light-microscopy based dense connectomic reconstruction
    of mammalian brain tissue,” <i>bioRxiv</i>. .
  ista: Tavakoli M, Lyudchik J, Januszewski M, Vistunou V, Agudelo Duenas N, Vorlaufer
    J, Sommer CM, Kreuzinger C, Oliveira B, Cenameri A, Novarino G, Jain V, Danzl
    JG. Light-microscopy based dense connectomic reconstruction of mammalian brain
    tissue. bioRxiv, <a href="https://doi.org/10.1101/2024.03.01.582884">10.1101/2024.03.01.582884</a>.
  mla: Tavakoli, Mojtaba, et al. “Light-Microscopy Based Dense Connectomic Reconstruction
    of Mammalian Brain Tissue.” <i>BioRxiv</i>, doi:<a href="https://doi.org/10.1101/2024.03.01.582884">10.1101/2024.03.01.582884</a>.
  short: M. Tavakoli, J. Lyudchik, M. Januszewski, V. Vistunou, N. Agudelo Duenas,
    J. Vorlaufer, C.M. Sommer, C. Kreuzinger, B. Oliveira, A. Cenameri, G. Novarino,
    V. Jain, J.G. Danzl, BioRxiv (n.d.).
corr_author: '1'
date_created: 2024-12-18T14:48:24Z
date_published: 2024-07-08T00:00:00Z
date_updated: 2026-04-28T13:33:34Z
day: '08'
department:
- _id: GaNo
- _id: JoDa
doi: 10.1101/2024.03.01.582884
ec_funded: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2024.03.01.582884
month: '07'
oa: 1
oa_version: Preprint
project:
- _id: 6285a163-2b32-11ec-9570-8e204ca2dba5
  grant_number: '26137'
  name: Studying Organelle Structure and Function at Nanoscale Resolution with Expansion
    Microscopy
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 34ba8964-11ca-11ed-8bc3-e15864e7e9a6
  grant_number: '101044865'
  name: Toward an understanding of the brain interstitial system and the extracellular
    proteome in health and autism spectrum disorders
- _id: 26AA4EF2-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232-B24
  name: Molecular Drug Targets
publication: bioRxiv
publication_status: draft
related_material:
  record:
  - id: '18681'
    relation: dissertation_contains
    status: public
  - id: '18674'
    relation: dissertation_contains
    status: public
  - id: '19704'
    relation: later_version
    status: public
status: public
title: Light-microscopy based dense connectomic reconstruction of mammalian brain
  tissue
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: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2024'
...
---
_id: '11160'
abstract:
- lang: eng
  text: Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent
    cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses
    macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency
    affects neurodevelopmental is unclear. Here, employing human cerebral organoids,
    we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories
    with an accelerated and delayed generation of, respectively, inhibitory and excitatory
    neurons that yields, at days 60 and 120, symmetrically opposite expansions in
    their proportions. This imbalance is consistent with an enlargement of cerebral
    organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic
    design of patient-specific mutations and mosaic organoids, we define genotype-phenotype
    relationships and uncover their cell-autonomous nature. Our results define cell-type-specific
    CHD8-dependent molecular defects related to an abnormal program of proliferation
    and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations,
    our study uncovers reproducible developmental alterations that may be employed
    for neurodevelopmental disease modeling.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: We thank Farnaz Freeman for technical assistance. This research was
  supported by the Scientific Service Units (SSU) of IST Austria through resources
  provided by the Bioimaging Facility (BIF) and the Life Science Facility (LSF). This
  work supported by the European Union’s Horizon 2020 research and innovation program
  (ERC) grant 715508 to G.N. (REVERSEAUTISM) and grant 825759 to G.T. (ENDpoiNTs);
  the Fondazione Cariplo 2017-0886 to A.L.T.; E-Rare-3 JTC 2018 IMPACT to M. Gabriele;
  and the Austrian Science Fund FWF I 4205-B to G.N. Graphical abstract and figures
  were created using BioRender.com.
article_number: '110615'
article_processing_charge: Yes
article_type: original
author:
- first_name: Carlo Emanuele
  full_name: Villa, Carlo Emanuele
  last_name: Villa
- first_name: Cristina
  full_name: Cheroni, Cristina
  last_name: Cheroni
- first_name: Christoph
  full_name: Dotter, Christoph
  id: 4C66542E-F248-11E8-B48F-1D18A9856A87
  last_name: Dotter
  orcid: 0000-0002-9033-9096
- first_name: Alejandro
  full_name: López-Tóbon, Alejandro
  last_name: López-Tóbon
- first_name: Bárbara
  full_name: Oliveira, Bárbara
  id: 3B03AA1A-F248-11E8-B48F-1D18A9856A87
  last_name: Oliveira
- first_name: Roberto
  full_name: Sacco, Roberto
  id: 42C9F57E-F248-11E8-B48F-1D18A9856A87
  last_name: Sacco
- first_name: Aysan Çerağ
  full_name: Yahya, Aysan Çerağ
  id: 365A65F8-F248-11E8-B48F-1D18A9856A87
  last_name: Yahya
- first_name: Jasmin
  full_name: Morandell, Jasmin
  id: 4739D480-F248-11E8-B48F-1D18A9856A87
  last_name: Morandell
- first_name: Michele
  full_name: Gabriele, Michele
  last_name: Gabriele
- first_name: Mojtaba
  full_name: Tavakoli, Mojtaba
  id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
  last_name: Tavakoli
  orcid: 0000-0002-7667-6854
- first_name: Julia
  full_name: Lyudchik, Julia
  id: 46E28B80-F248-11E8-B48F-1D18A9856A87
  last_name: Lyudchik
- 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: Mariano
  full_name: Gabitto, Mariano
  last_name: Gabitto
- 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: Giuseppe
  full_name: Testa, Giuseppe
  last_name: Testa
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
citation:
  ama: Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism
    to transient alterations in excitatory and inhibitory trajectories. <i>Cell Reports</i>.
    2022;39(1). doi:<a href="https://doi.org/10.1016/j.celrep.2022.110615">10.1016/j.celrep.2022.110615</a>
  apa: Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco,
    R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations
    in excitatory and inhibitory trajectories. <i>Cell Reports</i>. Elsevier. <a href="https://doi.org/10.1016/j.celrep.2022.110615">https://doi.org/10.1016/j.celrep.2022.110615</a>
  chicago: Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon,
    Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency
    Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.”
    <i>Cell Reports</i>. Elsevier, 2022. <a href="https://doi.org/10.1016/j.celrep.2022.110615">https://doi.org/10.1016/j.celrep.2022.110615</a>.
  ieee: C. E. Villa <i>et al.</i>, “CHD8 haploinsufficiency links autism to transient
    alterations in excitatory and inhibitory trajectories,” <i>Cell Reports</i>, vol.
    39, no. 1. Elsevier, 2022.
  ista: Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ,
    Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG,
    Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations
    in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615.
  mla: Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient
    Alterations in Excitatory and Inhibitory Trajectories.” <i>Cell Reports</i>, vol.
    39, no. 1, 110615, Elsevier, 2022, doi:<a href="https://doi.org/10.1016/j.celrep.2022.110615">10.1016/j.celrep.2022.110615</a>.
  short: C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco,
    A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer,
    M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022).
corr_author: '1'
date_created: 2022-04-15T09:03:10Z
date_published: 2022-04-05T00:00:00Z
date_updated: 2026-04-29T22:30:31Z
day: '05'
ddc:
- '570'
department:
- _id: JoDa
- _id: GaNo
doi: 10.1016/j.celrep.2022.110615
ec_funded: 1
external_id:
  isi:
  - '000785983900003'
  pmid:
  - '35385734'
file:
- access_level: open_access
  checksum: b4e8d68f0268dec499af333e6fd5d8e1
  content_type: application/pdf
  creator: dernst
  date_created: 2022-04-15T09:06:25Z
  date_updated: 2022-04-15T09:06:25Z
  file_id: '11164'
  file_name: 2022_CellReports_Villa.pdf
  file_size: '7808644'
  relation: main_file
  success: 1
file_date_updated: 2022-04-15T09:06:25Z
has_accepted_license: '1'
intvolume: '        39'
isi: 1
issue: '1'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
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: 2690FEAC-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: I04205
  name: Identification of converging Molecular Pathways Across Chromatinopathies as
    Targets for Therapy
publication: Cell Reports
publication_identifier:
  issn:
  - 2211-1247
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  record:
  - id: '18681'
    relation: dissertation_contains
    status: public
  - id: '18674'
    relation: dissertation_contains
    status: public
  - id: '12364'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: CHD8 haploinsufficiency links autism to transient alterations in excitatory
  and inhibitory trajectories
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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 39
year: '2022'
...
