Revealing the ultrastructure of the PNN in health and disease

The Perineuronal net (PNN) is a specialized form of extracellular matrix (ECM) which plays a crucial role in neuronal development, communication and memory retention. Moreover, the PNN provides a scaffold for regulatory proteins, isolates the neuron from the extracellular environment and protects it from radicals. The complex function of the PNN is accompanied by its intricate structure and composition. The PNN has a unique composition, rich with proteoglycans and glycoproteins coated with chondroitin sulfates. To investigate the ultrastructural hierarchy of the PNN I employed super-resolution expansion microscopy (ExM). In combination with specialized image analysis pipelines, I was able to generate a detailed 3D model of the PNN on a single cell. Interestingly, I observed a decline in PNN coverage and density in murine model for autism spectrum disorder (fragile X syndrome), Illuminating one of the main hallmarks of this syndrome. Building upon this initial data, I intend to understand the ultrastructure of the PNN and the changes it undergoes throughout life. This can reveal the molecular source of aging and neurodegenerative pathologies such as Alzheimer’s disease.