Brainbow: A Colorful Technique to Visualize Brain Circuitry

In November 2007 Jeff W. Lichtman and Joshua R. Sanes, both professors of Molecular & Cellular Biology in the Department of Neurobiology at Harvard Medical School, and colleagues, published "Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system," Nature 450 (7166): 56–62. doi:10.1038/nature06293. This described the visualization process they called "Brainbow."

"Detailed analysis of neuronal network architecture requires the development of new methods. Here we present strategies to visualize synaptic circuits by genetically labelling neurons with multiple, distinct colours. In Brainbow transgenes, Cre/lox recombination is used to create a stochastic choice of expression between three or more fluorescent proteins (XFPs). Integration of tandem Brainbow copies in transgenic mice yielded combinatorial XFP expression, and thus many colours, thereby providing a way to distinguish adjacent neurons and visualize other cellular interactions. As a demonstration, we reconstructed hundreds of neighbouring axons and multiple synaptic contacts in one small volume of a cerebellar lobe exhibiting approximately 90 colours. The expression in some lines also allowed us to map glial territories and follow glial cells and neurons over time in vivo. The ability of the Brainbow system to label uniquely many individual cells within a population may facilitate the analysis of neuronal circuitry on a large scale." (From the Nature abstract).