---
_id: '13267'
abstract:
- lang: eng
  text: Three-dimensional (3D) reconstruction of living brain tissue down to an individual
    synapse level would create opportunities for decoding the dynamics and structure–function
    relationships of the brain’s complex and dense information processing network;
    however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise
    ratio and prohibitive light burden in optical imaging, whereas electron microscopy
    is inherently static. Here we solved these challenges by developing an integrated
    optical/machine-learning technology, LIONESS (live information-optimized nanoscopy
    enabling saturated segmentation). This leverages optical modifications to stimulated
    emission depletion microscopy in comprehensively, extracellularly labeled tissue
    and previous information on sample structure via machine learning to simultaneously
    achieve isotropic super-resolution, high signal-to-noise ratio and compatibility
    with living tissue. This allows dense deep-learning-based instance segmentation
    and 3D reconstruction at a synapse level, incorporating molecular, activity and
    morphodynamic information. LIONESS opens up avenues for studying the dynamic functional
    (nano-)architecture of living brain tissue.
acknowledged_ssus:
- _id: ScienComp
- _id: Bio
- _id: PreCl
- _id: E-Lib
- _id: LifeSc
- _id: M-Shop
acknowledgement: "We thank J. Vorlaufer, N. Agudelo and A. Wartak for microscope maintenance
  and troubleshooting, C. Kreuzinger and A. Freeman for technical assistance, M. Šuplata
  for hardware control support and M. Cunha dos Santos for initial exploration of
  software. We\r\nthank P. Henderson for advice on deep-learning training and M. Sixt,
  S. Boyd and T. Weiss for discussions and critical reading of the manuscript. L.
  Lavis (Janelia Research Campus) generously provided the JF585-HaloTag ligand. We
  acknowledge expert support by IST\r\nAustria’s scientific computing, imaging and
  optics, preclinical, library and laboratory support facilities and by the Miba machine
  shop. We gratefully acknowledge funding by the following sources: Austrian Science
  Fund (F.W.F.) grant no. I3600-B27 (J.G.D.), grant no. DK W1232\r\n(J.G.D. and J.M.M.)
  and grant no. Z 312-B27, Wittgenstein award (P.J.); the Gesellschaft für Forschungsförderung
  NÖ grant no. LSC18-022 (J.G.D.); an ISTA Interdisciplinary project grant (J.G.D.
  and B.B.); the European Union’s Horizon 2020 research and innovation programme,\r\nMarie-Skłodowska
  Curie grant 665385 (J.M.M. and J.L.); the European Union’s Horizon 2020 research
  and innovation programme, European Research Council grant no. 715767, MATERIALIZABLE
  (B.B.); grant no. 715508, REVERSEAUTISM (G.N.); grant no. 695568, SYNNOVATE (S.G.N.G.);
  and grant no. 692692, GIANTSYN (P.J.); the Simons\r\nFoundation Autism Research
  Initiative grant no. 529085 (S.G.N.G.); the Wellcome Trust Technology Development
  grant no. 202932 (S.G.N.G.); the Marie Skłodowska-Curie Actions Individual Fellowship
  no. 101026635 under the EU Horizon 2020 program (J.F.W.);\r\nthe Human Frontier
  Science Program postdoctoral fellowship LT000557/2018 (W.J.); and the National Science
  Foundation grant no. IIS-1835231 (H.P.) and NCS-FO-2124179 (H.P.)."
article_processing_charge: Yes
article_type: original
author:
- first_name: Philipp
  full_name: Velicky, Philipp
  id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
  last_name: Velicky
  orcid: 0000-0002-2340-7431
- first_name: Eder
  full_name: Miguel Villalba, Eder
  id: 3FB91342-F248-11E8-B48F-1D18A9856A87
  last_name: Miguel Villalba
  orcid: 0000-0001-5665-0430
- first_name: Julia M
  full_name: Michalska, Julia M
  id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
  last_name: Michalska
  orcid: 0000-0003-3862-1235
- first_name: Julia
  full_name: Lyudchik, Julia
  id: 46E28B80-F248-11E8-B48F-1D18A9856A87
  last_name: Lyudchik
- first_name: Donglai
  full_name: Wei, Donglai
  last_name: Wei
- first_name: Zudi
  full_name: Lin, Zudi
  last_name: Lin
- first_name: Jake
  full_name: Watson, Jake
  id: 63836096-4690-11EA-BD4E-32803DDC885E
  last_name: Watson
  orcid: 0000-0002-8698-3823
- first_name: Jakob
  full_name: Troidl, Jakob
  last_name: Troidl
- first_name: Johanna
  full_name: Beyer, Johanna
  last_name: Beyer
- first_name: Yoav
  full_name: Ben Simon, Yoav
  id: 43DF3136-F248-11E8-B48F-1D18A9856A87
  last_name: Ben Simon
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Wiebke
  full_name: Jahr, Wiebke
  id: 425C1CE8-F248-11E8-B48F-1D18A9856A87
  last_name: Jahr
- first_name: Alban
  full_name: Cenameri, Alban
  id: 9ac8f577-2357-11eb-997a-e566c5550886
  last_name: Cenameri
- first_name: Johannes
  full_name: Broichhagen, Johannes
  last_name: Broichhagen
- first_name: Seth G.N.
  full_name: Grant, Seth G.N.
  last_name: Grant
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Hanspeter
  full_name: Pfister, Hanspeter
  last_name: Pfister
- first_name: Bernd
  full_name: Bickel, Bernd
  id: 49876194-F248-11E8-B48F-1D18A9856A87
  last_name: Bickel
  orcid: 0000-0001-6511-9385
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
citation:
  ama: Velicky P, Miguel Villalba E, Michalska JM, et al. Dense 4D nanoscale reconstruction
    of living brain tissue. <i>Nature Methods</i>. 2023;20:1256-1265. doi:<a href="https://doi.org/10.1038/s41592-023-01936-6">10.1038/s41592-023-01936-6</a>
  apa: Velicky, P., Miguel Villalba, E., Michalska, J. M., Lyudchik, J., Wei, D.,
    Lin, Z., … Danzl, J. G. (2023). Dense 4D nanoscale reconstruction of living brain
    tissue. <i>Nature Methods</i>. Springer Nature. <a href="https://doi.org/10.1038/s41592-023-01936-6">https://doi.org/10.1038/s41592-023-01936-6</a>
  chicago: Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Julia Lyudchik,
    Donglai Wei, Zudi Lin, Jake Watson, et al. “Dense 4D Nanoscale Reconstruction
    of Living Brain Tissue.” <i>Nature Methods</i>. Springer Nature, 2023. <a href="https://doi.org/10.1038/s41592-023-01936-6">https://doi.org/10.1038/s41592-023-01936-6</a>.
  ieee: P. Velicky <i>et al.</i>, “Dense 4D nanoscale reconstruction of living brain
    tissue,” <i>Nature Methods</i>, vol. 20. Springer Nature, pp. 1256–1265, 2023.
  ista: Velicky P, Miguel Villalba E, Michalska JM, Lyudchik J, Wei D, Lin Z, Watson
    J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen
    J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. 2023. Dense
    4D nanoscale reconstruction of living brain tissue. Nature Methods. 20, 1256–1265.
  mla: Velicky, Philipp, et al. “Dense 4D Nanoscale Reconstruction of Living Brain
    Tissue.” <i>Nature Methods</i>, vol. 20, Springer Nature, 2023, pp. 1256–65, doi:<a
    href="https://doi.org/10.1038/s41592-023-01936-6">10.1038/s41592-023-01936-6</a>.
  short: P. Velicky, E. Miguel Villalba, J.M. Michalska, J. Lyudchik, D. Wei, Z. Lin,
    J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri,
    J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel,
    J.G. Danzl, Nature Methods 20 (2023) 1256–1265.
date_created: 2023-07-23T22:01:13Z
date_published: 2023-08-01T00:00:00Z
date_updated: 2024-01-10T08:37:48Z
day: '01'
department:
- _id: PeJo
- _id: GaNo
- _id: BeBi
- _id: JoDa
- _id: Bio
doi: 10.1038/s41592-023-01936-6
ec_funded: 1
external_id:
  isi:
  - '001025621500001'
  pmid:
  - '37429995'
intvolume: '        20'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1038/s41592-023-01936-6
month: '08'
oa: 1
oa_version: Published Version
page: 1256-1265
pmid: 1
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: I03600
  name: Optical control of synaptic function via adhesion molecules
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232-B24
  name: Molecular Drug Targets
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z00312
  name: The Wittgenstein Prize
- _id: 23889792-32DE-11EA-91FC-C7463DDC885E
  name: High content imaging to decode human immune cell interactions in health and
    allergic disease
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 24F9549A-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715767'
  name: 'MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and
    Modeling'
- _id: 25444568-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715508'
  name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
    and in vitro Models
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
  call_identifier: H2020
  grant_number: '101026635'
  name: Synaptic computations of the hippocampal CA3 circuitry
- _id: 2668BFA0-B435-11E9-9278-68D0E5697425
  grant_number: LT00057
  name: High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration
publication: Nature Methods
publication_identifier:
  eissn:
  - 1548-7105
  issn:
  - 1548-7091
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - relation: software
    url: https://github.com/danzllab/LIONESS
  record:
  - id: '12817'
    relation: research_data
    status: public
  - id: '14770'
    relation: shorter_version
    status: public
scopus_import: '1'
status: public
title: Dense 4D nanoscale reconstruction of living brain tissue
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 20
year: '2023'
...
---
_id: '14257'
abstract:
- lang: eng
  text: Mapping the complex and dense arrangement of cells and their connectivity
    in brain tissue demands nanoscale spatial resolution imaging. Super-resolution
    optical microscopy excels at visualizing specific molecules and individual cells
    but fails to provide tissue context. Here we developed Comprehensive Analysis
    of Tissues across Scales (CATS), a technology to densely map brain tissue architecture
    from millimeter regional to nanometer synaptic scales in diverse chemically fixed
    brain preparations, including rodent and human. CATS uses fixation-compatible
    extracellular labeling and optical imaging, including stimulated emission depletion
    or expansion microscopy, to comprehensively delineate cellular structures. It
    enables three-dimensional reconstruction of single synapses and mapping of synaptic
    connectivity by identification and analysis of putative synaptic cleft regions.
    Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed
    and quantified the synaptic input and output structure of identified neurons.
    We furthermore demonstrate applicability to clinically derived human tissue samples,
    including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing
    the cellular architecture of brain tissue in health and disease.
acknowledged_ssus:
- _id: ScienComp
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
- _id: E-Lib
acknowledgement: 'We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak
  for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I.
  Erber for technical assistance; and M. Tomschik for support with obtaining human
  samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata
  for computational support and hardware control. We are grateful to R. Shigemoto
  and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University)
  for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly
  provided by S. Grant (University of Edinburgh). We acknowledge expert support by
  Institute of Science and Technology Austria’s scientific computing, imaging and
  optics, preclinical and lab support facilities and by the Miba machine shop and
  library. We gratefully acknowledge funding by the following sources: Austrian Science
  Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232
  (J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award
  (P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27
  (R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.);
  European Union’s Horizon 2020 research and innovation programme, European Research
  Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020
  research and innovation programme, European Research Council (ERC) grant 692692
  – GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under
  the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions
  Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).'
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Julia M
  full_name: Michalska, Julia M
  id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
  last_name: Michalska
  orcid: 0000-0003-3862-1235
- first_name: Julia
  full_name: Lyudchik, Julia
  id: 46E28B80-F248-11E8-B48F-1D18A9856A87
  last_name: Lyudchik
- first_name: Philipp
  full_name: Velicky, Philipp
  id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
  last_name: Velicky
  orcid: 0000-0002-2340-7431
- first_name: Hana
  full_name: Korinkova, Hana
  id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed
  last_name: Korinkova
- first_name: Jake
  full_name: Watson, Jake
  id: 63836096-4690-11EA-BD4E-32803DDC885E
  last_name: Watson
  orcid: 0000-0002-8698-3823
- first_name: Alban
  full_name: Cenameri, Alban
  id: 9ac8f577-2357-11eb-997a-e566c5550886
  last_name: Cenameri
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Nicole
  full_name: Amberg, Nicole
  id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
  last_name: Amberg
  orcid: 0000-0002-3183-8207
- first_name: Alessandro
  full_name: Venturino, Alessandro
  id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
  last_name: Venturino
  orcid: 0000-0003-2356-9403
- first_name: Karl
  full_name: Roessler, Karl
  last_name: Roessler
- first_name: Thomas
  full_name: Czech, Thomas
  last_name: Czech
- first_name: Romana
  full_name: Höftberger, Romana
  last_name: Höftberger
- first_name: Sandra
  full_name: Siegert, Sandra
  id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
  last_name: Siegert
  orcid: 0000-0001-8635-0877
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
citation:
  ama: Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture
    across millimeter to nanometer scales. <i>Nature Biotechnology</i>. 2023. doi:<a
    href="https://doi.org/10.1038/s41587-023-01911-8">10.1038/s41587-023-01911-8</a>
  apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri,
    A., … Danzl, J. G. (2023). Imaging brain tissue architecture across millimeter
    to nanometer scales. <i>Nature Biotechnology</i>. Springer Nature. <a href="https://doi.org/10.1038/s41587-023-01911-8">https://doi.org/10.1038/s41587-023-01911-8</a>
  chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake
    Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture
    across Millimeter to Nanometer Scales.” <i>Nature Biotechnology</i>. Springer
    Nature, 2023. <a href="https://doi.org/10.1038/s41587-023-01911-8">https://doi.org/10.1038/s41587-023-01911-8</a>.
  ieee: J. M. Michalska <i>et al.</i>, “Imaging brain tissue architecture across millimeter
    to nanometer scales,” <i>Nature Biotechnology</i>. Springer Nature, 2023.
  ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer
    CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino
    G, Jonas PM, Danzl JG. 2023. Imaging brain tissue architecture across millimeter
    to nanometer scales. Nature Biotechnology.
  mla: Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter
    to Nanometer Scales.” <i>Nature Biotechnology</i>, Springer Nature, 2023, doi:<a
    href="https://doi.org/10.1038/s41587-023-01911-8">10.1038/s41587-023-01911-8</a>.
  short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri,
    C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S.
    Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology (2023).
date_created: 2023-09-03T22:01:15Z
date_published: 2023-08-31T00:00:00Z
date_updated: 2024-02-21T12:18:18Z
day: '31'
department:
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: JoDa
- _id: Bio
- _id: RySh
doi: 10.1038/s41587-023-01911-8
ec_funded: 1
external_id:
  isi:
  - '001065254200001'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1038/s41587-023-01911-8
month: '08'
oa: 1
oa_version: Published Version
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: I03600
  name: Optical control of synaptic function via adhesion molecules
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232-B24
  name: Molecular Drug Targets
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z00312
  name: The Wittgenstein Prize
- _id: 23889792-32DE-11EA-91FC-C7463DDC885E
  name: High content imaging to decode human immune cell interactions in health and
    allergic disease
- _id: 25444568-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715508'
  name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
    and in vitro Models
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
  call_identifier: H2020
  grant_number: '101026635'
  name: Synaptic computations of the hippocampal CA3 circuitry
publication: Nature Biotechnology
publication_identifier:
  eissn:
  - 1546-1696
  issn:
  - 1087-0156
publication_status: epub_ahead
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - relation: software
    url: https://github.com/danzllab/CATS
  record:
  - id: '13126'
    relation: research_data
    status: public
scopus_import: '1'
status: public
title: Imaging brain tissue architecture across millimeter to nanometer scales
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2023'
...
---
_id: '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).
date_created: 2022-04-15T09:03:10Z
date_published: 2022-04-05T00:00:00Z
date_updated: 2024-03-25T23:30:25Z
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:
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  date_created: 2022-04-15T09:06:25Z
  date_updated: 2022-04-15T09:06:25Z
  file_id: '11164'
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  relation: main_file
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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: '12364'
    relation: dissertation_contains
    status: public
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'
...
---
_id: '11950'
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 nanoscopic synaptic scales in diverse chemically fixed
    brain preparations, including rodent and human. CATS leverages fixation-compatible
    extracellular labeling and advanced optical readout, in particular stimulated-emission
    depletion and expansion microscopy, to comprehensively delineate cellular structures.
    It enables 3D-reconstructing single synapses and mapping synaptic connectivity
    by identification and tailored analysis of putative synaptic cleft regions. Applying
    CATS to the hippocampal mossy fiber circuitry, we demonstrate its power to reveal
    the system’s molecularly informed ultrastructure across spatial scales and assess
    local connectivity by reconstructing and quantifying the synaptic input and output
    structure of identified neurons.
article_processing_charge: No
author:
- first_name: Julia M
  full_name: Michalska, Julia M
  id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
  last_name: Michalska
  orcid: 0000-0003-3862-1235
- 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: 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: 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. Uncovering brain tissue architecture
    across scales with super-resolution light microscopy. <i>bioRxiv</i>. doi:<a href="https://doi.org/10.1101/2022.08.17.504272">10.1101/2022.08.17.504272</a>
  apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri,
    A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales
    with super-resolution light microscopy. <i>bioRxiv</i>. Cold Spring Harbor Laboratory.
    <a href="https://doi.org/10.1101/2022.08.17.504272">https://doi.org/10.1101/2022.08.17.504272</a>
  chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake
    Watson, Alban Cenameri, Christoph M Sommer, et al. “Uncovering Brain Tissue Architecture
    across Scales with Super-Resolution Light Microscopy.” <i>BioRxiv</i>. Cold Spring
    Harbor Laboratory, n.d. <a href="https://doi.org/10.1101/2022.08.17.504272">https://doi.org/10.1101/2022.08.17.504272</a>.
  ieee: J. M. Michalska <i>et al.</i>, “Uncovering brain tissue architecture across
    scales with super-resolution light microscopy,” <i>bioRxiv</i>. Cold Spring Harbor
    Laboratory.
  ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer
    CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG.
    Uncovering brain tissue architecture across scales with super-resolution light
    microscopy. bioRxiv, <a href="https://doi.org/10.1101/2022.08.17.504272">10.1101/2022.08.17.504272</a>.
  mla: Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales
    with Super-Resolution Light Microscopy.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory,
    doi:<a href="https://doi.org/10.1101/2022.08.17.504272">10.1101/2022.08.17.504272</a>.
  short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri,
    C.M. Sommer, A. Venturino, K. Roessler, T. Czech, S. Siegert, G. Novarino, P.M.
    Jonas, J.G. Danzl, BioRxiv (n.d.).
date_created: 2022-08-24T08:24:52Z
date_published: 2022-08-18T00:00:00Z
date_updated: 2024-03-25T23:30:11Z
day: '18'
department:
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: JoDa
doi: 10.1101/2022.08.17.504272
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2022.08.17.504272
month: '08'
oa: 1
oa_version: Preprint
publication: bioRxiv
publication_status: submitted
publisher: Cold Spring Harbor Laboratory
related_material:
  record:
  - id: '12470'
    relation: dissertation_contains
    status: public
status: public
title: Uncovering brain tissue architecture across scales with super-resolution light
  microscopy
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
