---
OA_place: publisher
OA_type: hybrid
_id: '14257'
abstract:
- lang: eng
  text: Mapping the complex and dense arrangement of cells and their connectivity
    in brain tissue demands nanoscale spatial resolution imaging. Super-resolution
    optical microscopy excels at visualizing specific molecules and individual cells
    but fails to provide tissue context. Here we developed Comprehensive Analysis
    of Tissues across Scales (CATS), a technology to densely map brain tissue architecture
    from millimeter regional to nanometer synaptic scales in diverse chemically fixed
    brain preparations, including rodent and human. CATS uses fixation-compatible
    extracellular labeling and optical imaging, including stimulated emission depletion
    or expansion microscopy, to comprehensively delineate cellular structures. It
    enables three-dimensional reconstruction of single synapses and mapping of synaptic
    connectivity by identification and analysis of putative synaptic cleft regions.
    Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed
    and quantified the synaptic input and output structure of identified neurons.
    We furthermore demonstrate applicability to clinically derived human tissue samples,
    including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing
    the cellular architecture of brain tissue in health and disease.
acknowledged_ssus:
- _id: ScienComp
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
- _id: E-Lib
acknowledgement: 'We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak
  for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I.
  Erber for technical assistance; and M. Tomschik for support with obtaining human
  samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata
  for computational support and hardware control. We are grateful to R. Shigemoto
  and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University)
  for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly
  provided by S. Grant (University of Edinburgh). We acknowledge expert support by
  Institute of Science and Technology Austria’s scientific computing, imaging and
  optics, preclinical and lab support facilities and by the Miba machine shop and
  library. We gratefully acknowledge funding by the following sources: Austrian Science
  Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232
  (J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award
  (P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27
  (R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.);
  European Union’s Horizon 2020 research and innovation programme, European Research
  Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020
  research and innovation programme, European Research Council (ERC) grant 692692
  – GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under
  the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions
  Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).'
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Julia M
  full_name: Michalska, Julia M
  id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
  last_name: Michalska
  orcid: 0000-0003-3862-1235
- first_name: Julia
  full_name: Lyudchik, Julia
  id: 46E28B80-F248-11E8-B48F-1D18A9856A87
  last_name: Lyudchik
- first_name: Philipp
  full_name: Velicky, Philipp
  id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
  last_name: Velicky
  orcid: 0000-0002-2340-7431
- first_name: Hana
  full_name: Korinkova, Hana
  id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed
  last_name: Korinkova
- first_name: Jake
  full_name: Watson, Jake
  id: 63836096-4690-11EA-BD4E-32803DDC885E
  last_name: Watson
  orcid: 0000-0002-8698-3823
- first_name: Alban
  full_name: Cenameri, Alban
  id: 9ac8f577-2357-11eb-997a-e566c5550886
  last_name: Cenameri
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Nicole
  full_name: Amberg, Nicole
  id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
  last_name: Amberg
  orcid: 0000-0002-3183-8207
- first_name: Alessandro
  full_name: Venturino, Alessandro
  id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
  last_name: Venturino
  orcid: 0000-0003-2356-9403
- first_name: Karl
  full_name: Roessler, Karl
  last_name: Roessler
- first_name: Thomas
  full_name: Czech, Thomas
  last_name: Czech
- first_name: Romana
  full_name: Höftberger, Romana
  last_name: Höftberger
- first_name: Sandra
  full_name: Siegert, Sandra
  id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
  last_name: Siegert
  orcid: 0000-0001-8635-0877
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
citation:
  ama: Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture
    across millimeter to nanometer scales. <i>Nature Biotechnology</i>. 2024;42:1051-1064.
    doi:<a href="https://doi.org/10.1038/s41587-023-01911-8">10.1038/s41587-023-01911-8</a>
  apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri,
    A., … Danzl, J. G. (2024). Imaging brain tissue architecture across millimeter
    to nanometer scales. <i>Nature Biotechnology</i>. Springer Nature. <a href="https://doi.org/10.1038/s41587-023-01911-8">https://doi.org/10.1038/s41587-023-01911-8</a>
  chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake
    Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture
    across Millimeter to Nanometer Scales.” <i>Nature Biotechnology</i>. Springer
    Nature, 2024. <a href="https://doi.org/10.1038/s41587-023-01911-8">https://doi.org/10.1038/s41587-023-01911-8</a>.
  ieee: J. M. Michalska <i>et al.</i>, “Imaging brain tissue architecture across millimeter
    to nanometer scales,” <i>Nature Biotechnology</i>, vol. 42. Springer Nature, pp.
    1051–1064, 2024.
  ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer
    CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino
    G, Jonas PM, Danzl JG. 2024. Imaging brain tissue architecture across millimeter
    to nanometer scales. Nature Biotechnology. 42, 1051–1064.
  mla: Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter
    to Nanometer Scales.” <i>Nature Biotechnology</i>, vol. 42, Springer Nature, 2024,
    pp. 1051–64, doi:<a href="https://doi.org/10.1038/s41587-023-01911-8">10.1038/s41587-023-01911-8</a>.
  short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri,
    C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S.
    Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology 42 (2024) 1051–1064.
corr_author: '1'
date_created: 2023-09-03T22:01:15Z
date_published: 2024-07-01T00:00:00Z
date_updated: 2026-04-14T08:34:35Z
day: '01'
ddc:
- '570'
department:
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: JoDa
- _id: Bio
- _id: RySh
doi: 10.1038/s41587-023-01911-8
ec_funded: 1
external_id:
  isi:
  - '001065254200001'
  pmid:
  - '37653226'
file:
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  date_created: 2025-01-09T07:48:01Z
  date_updated: 2025-01-09T07:48:01Z
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file_date_updated: 2025-01-09T07:48:01Z
has_accepted_license: '1'
intvolume: '        42'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 1051-1064
pmid: 1
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: I03600
  name: Optical control of synaptic function via adhesion molecules
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232
  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
publication: Nature Biotechnology
publication_identifier:
  eissn:
  - 1546-1696
  issn:
  - 1087-0156
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - relation: software
    url: https://github.com/danzllab/CATS
  record:
  - id: '18660'
    relation: dissertation_contains
    status: deleted
  - id: '13126'
    relation: research_data
    status: public
  - id: '18674'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Imaging brain tissue architecture across millimeter to nanometer scales
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: 42
year: '2024'
...