Photo-transformable genetically-encoded optical probes for functional highlighting in vivo

Studying the brain requires knowledge about both structure (i.e., connectome) and function of its constituents (neurons and glia alike). This need has prompted the development of novel tools and techniques, in particular optical techniques to examine cells remotely. Early works (1900's) led to the development of novel cell-staining techniques that, when combined with the use of a very simple light microscope, visualized individual neurons and their subcellular compartments in fixed tissues. Today, highlighting of structure and function can be performed on live cells, notably in vivo, owing to discovery of GFP and subsequent development of genetically encoded fluorescent optical tools. In this review, we focus our attention on a subset of optical biosensors, namely probes whose emission can be modified by light. We designate them photo-transformable genetically encoded probes. The family of photo-transformable probes embraces current probes that undergo photoactivation (PA), photoconversion (PC) or photoswitching (PS). We argue that these are particularly suited for studying multiple features of neurons, such as structure, connectivity and function concomitantly, for functional highlighting of neurons in vivo.