In vivo super-resolution of the brain – How to visualize the hidden nanoplasticity?

Super-resolution fluorescence microscopy has entered most biological laboratories worldwide and its benefit is undisputable. Its application to brain imaging, for example in living mice, enables the study of sub-cellular structural plasticity and brain function directly in a living mammal. The demands of brain imaging on the different super-resolution microscopy techniques (STED, RESOLFT, SIM, ISM) and labeling strategies are discussed here as well as the challenges of the required cranial window preparation. Applications of super-resolution in the anesthetized mouse brain enlighten the stability and plasticity of synaptic nanostructures. These studies show the potential of in vivo super-resolution imaging and justify its application more widely in vivo to investigate the role of nanostructures in memory and learning.