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Julia Michalska, Julia Lyudchik,Philipp Velicky, Hana Korinkova, Jake F. Watson, Alban Cenameri, Christoph Sommer, Johann Danzl (Institute of Science and Technology Austria, Am Campus 1, Klosterneuburg, Austria)
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), an integrated labeling, optical imaging, and analysis platform to decode brain tissue architecture, subcellular morphologies, and molecular arrangements within their structural context. We engineered CATS to visualize all cellular structures in fixed tissue by extracellular labeling with (super-resolution) fluorescence microscopy. 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.https://www.biorxiv.org/content/10.1101/2022.08.17.504272v1.full