Microscopy Club Lecture

Johann Georg Danzl from the Institute of Science and Technology Austria, Klosterneuburg, Austria will talk about “Uncovering brain tissue architecture with super-resolution light microscopy” during the MBExC Microscopy Club.

Abstract
Light-microscopy based reconstruction of brain tissue down to individual synapse level would create major opportunities for decoding the dynamics and structure-function relationships of this tantalizingly complex and densely arranged biological tissue underlying all information processing in the brain. However, it 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 and access to molecular information requires complex correlative workflows.
To solve these challenges, we developed an integrated optical/machine learning technology, LIONESS (Live Information-Optimized Nanoscopy Enabling Saturated Segmentation) [1]. It leverages optical modifications to STED microscopy in comprehensively labelled tissue and uses prior information on sample structure via deep learning-based image restoration 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 synapse level incorporating molecular, activity, and morphodynamic information.
In a complementary approach, which we termed CATS (Comprehensive Analysis of Tissues across Scales) [2], we visualize tissue architecture from the organ to subcellular nanoscopic scales by selectively labelling the extracellular compartment and employing super-resolution imaging in the fixed state. This opens up further possibilities for molecular labelling and choice of imaging modality, including expansion microscopy for large-scale tissue imaging. CATS enables 3D-reconstructing single synapses and mapping synaptic connectivity by identification and tailored analysis of putative synaptic cleft regions. It also allows studying diverse sample types, including human clinical specimens.
These approaches open up major avenues for studying the functional (nano-)architecture of brain tissue, which I will exemplify in applications to the hippocampal mossy fiber circuitry. 
[1] https://doi.org/10.1101/2022.03.16.484431;
[2] https://doi.org/10.1101/2022.08.17.504272.

Hosts: Carola Gregor (IFNANO), Jan Huisken (U GOE), Eri Sakata (UMG)
Local organizers: Alexander Egner (IFNANO), Jörg Enderlein (U GOE), MBExC

Location: Institut für Nanophotonik (IFNANO), Seminar Room, Hans-Adolf-Krebs Weg 1, 37077 Göttingen

Please find here the poster of the talk: