Getting sharper: the brain under the spotlight of super-resolution microscopy

Brain cells such as neurons and astrocytes exhibit an extremely elaborate mor-phology, and their functional specializations like synapses and glial processes often fall below the resolution limit of conventional light microscopy. This is a huge obstacle for neurobiologists because the nanoarchitecture critically shapes fundamental functions like synaptic transmission and Ca2+ signaling. Super -resolution microscopy can overcome this problem, offering the chance to visual-ize the structural and molecular organization of brain cells in a living and dynamic tissue context, unlike traditional methods like electron microscopy or atomic force microscopy. This review covers the basic principles of the main super-resolution microscopy techniques in use today and explains how their specific strengths can illuminate the nanoscale mechanisms that govern brain physiology.