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Updated: Jun 28, 2025
Super-Resolution Imaging to Study Co-Localization of Proteins and Synaptic Markers in Primary Neurons
Published on: October 31, 2020
Combined expansion and STED microscopy reveals altered fingerprints of postsynaptic nanostructure across brain
Jan Philipp Delling1,2, Helen Friedericke Bauer3, Susanne Gerlach-Arbeiter3
1Institute of Anatomy and Cell Biology, Ulm University, Ulm, 89081, Germany. jan.delling@alumni.uni-ulm.de.
Abstract:
Synaptic dysfunction is a key feature of SHANK-associated disorders such as autism spectrum disorder, schizophrenia, and Phelan-McDermid syndrome. Since detailed knowledge of their effect on synaptic nanostructure remains limited, we aimed to investigate such alterations in ex11|SH3 SHANK3-KO mice combining expansion and STED microscopy. This enabled high-resolution imaging of mosaic-like arrangements formed by synaptic proteins in both human and murine brain tissue. We found distinct shape-profiles as fingerprints of the murine postsynaptic scaffold across brain regions and genotypes, as well as alterations in the spatial and molecular organization of subsynaptic domains under SHANK3-deficient conditions. These results provide insights into synaptic nanostructure in situ and advance our understanding of molecular mechanisms underlying synaptic dysfunction in neuropsychiatric disorders.
