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Uncovering brain tissue architecture across scales with super-resolution light microscopy

View ORCID ProfileJulia M. Michalska, Julia Lyudchik, View ORCID ProfilePhilipp Velicky, Hana Korinkova, View ORCID ProfileJake F. Watson, Alban Cenameri, View ORCID ProfileChristoph Sommer, View ORCID ProfileAlessandro Venturino, View ORCID ProfileKarl Roessler, View ORCID ProfileThomas Czech, View ORCID ProfileSandra Siegert, View ORCID ProfileGaia Novarino, View ORCID ProfilePeter Jonas, View ORCID ProfileJohann G. Danzl
doi: https://doi.org/10.1101/2022.08.17.504272
Julia M. Michalska
1Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria
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Julia Lyudchik
1Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria
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Philipp Velicky
1Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria
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Hana Korinkova
1Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria
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Jake F. Watson
1Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria
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Alban Cenameri
1Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria
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Christoph Sommer
1Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria
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Alessandro Venturino
1Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria
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  • ORCID record for Alessandro Venturino
Karl Roessler
2Medical University of Vienna, Department of Neurosurgery, Waehringer Guertel 18-20, 1090 Vienna, Austria
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Thomas Czech
2Medical University of Vienna, Department of Neurosurgery, Waehringer Guertel 18-20, 1090 Vienna, Austria
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Sandra Siegert
1Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria
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  • ORCID record for Sandra Siegert
Gaia Novarino
1Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria
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  • ORCID record for Gaia Novarino
Peter Jonas
1Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria
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Johann G. Danzl
1Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria
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  • ORCID record for Johann G. Danzl
  • For correspondence: johann.danzl@ist.ac.at
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Abstract

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.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 18, 2022.
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Uncovering brain tissue architecture across scales with super-resolution light microscopy
Julia M. Michalska, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake F. Watson, Alban Cenameri, Christoph Sommer, Alessandro Venturino, Karl Roessler, Thomas Czech, Sandra Siegert, Gaia Novarino, Peter Jonas, Johann G. Danzl
bioRxiv 2022.08.17.504272; doi: https://doi.org/10.1101/2022.08.17.504272
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Uncovering brain tissue architecture across scales with super-resolution light microscopy
Julia M. Michalska, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake F. Watson, Alban Cenameri, Christoph Sommer, Alessandro Venturino, Karl Roessler, Thomas Czech, Sandra Siegert, Gaia Novarino, Peter Jonas, Johann G. Danzl
bioRxiv 2022.08.17.504272; doi: https://doi.org/10.1101/2022.08.17.504272

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