Imaging brain tissue architecture across millimeter to nanometer scales

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.


Journal Article | Epub ahead of print | English

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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 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.
Publishing Year
Date Published
2023-08-31
Journal Title
Nature Biotechnology
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.).
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Cite this

Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. 2023. doi:10.1038/s41587-023-01911-8
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. Nature Biotechnology. Springer Nature. https://doi.org/10.1038/s41587-023-01911-8
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.” Nature Biotechnology. Springer Nature, 2023. https://doi.org/10.1038/s41587-023-01911-8.
J. M. Michalska et al., “Imaging brain tissue architecture across millimeter to nanometer scales,” Nature Biotechnology. Springer Nature, 2023.
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.
Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Nature Biotechnology, Springer Nature, 2023, doi:10.1038/s41587-023-01911-8.
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