June 2013

The study of brain-structure-function relationships is complex and often involves multiple steps that do not allow simultaneous investigation of properties in the same specimen. These investigators have overcome this problem by morphing intact tissue into an optically transparent and macromoleculepermeable construct that preserves native structure. The tissue is transformed into a nanoporous hydrogel-hybridized form crosslinked to a three-dimensional network of hydrophilic polymers. In this way, they can image fine structural features such as membrane localized proteins, synapse and spines in place in a whole brain. At the same time, they can perform multipleround molecular phenotyping of the intact tissue using rapidly diffusible probes. This technique is applicable to any tissue from zebrafish to long-banked human tissue. While this technique does not supplant electron microscopy, it can provide access to structural and molecular information at the limits of light microscopy. The term CLARITY was adopted as an acronym for Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging/Immunostaining/In situ hybridization-compatible Tissue hYdrogel. However, the technique need not be acrylamide or hydrogel based and the properties of the infused elements can be adjusted for varying degrees of clarity or other functionality. This technique will allow investigators to marry whole brain imaging with molecular identification in a way that will enable more exact study of the biological basis of disease (Nature 2013;497:332–337).