If you have the time, pick up a copy of the latest Nature. There is a paper that describes how a lab, based here at Harvard Medical School, used a random gene splicing strategy to express various fluorescent proteins in each neuron inside of the brain of a transgenic mouse. As a result of the random splicing event (using a cre/lox recombination system), each neuron expressed a different subset of the fluorescent proteins. Here is an example of the brainbow mouse’s mosaic brain:
So, how many distinguishable colors did the different cells express?
To determine [the number of distinguishable colors], we analysed the distribution of colour profiles in the reconstructed volume from line H above (eight transgene copies). The population of axons exhibited many different colour profiles (Fig. 5c); the mean colour values calculated for the different axons varied greatly in hue and saturation and filled a large portion of colour space (Supplementary Fig. 5c). Using a visual colour discrimination test, we found that 98.9% of randomly selected rosette pairs expressed colours distinct enough to discriminate (see Methods). This degree of colour variation is equivalent to having approximately 89 distinct colours (that is, if 98.9% of axon pairs appear different, then the remaining 1.1% or 1 out of 88.7 pairs are too similar to discriminate). An alternative computer-based colour analysis of hippocampal neuron cell bodies from Brainbow-1.0 line L (see Fig. 4c) gave an estimated 166 colours. This large number of colours should be useful in resolving individual components of many neural circuits.
Again from the article:
Given the colour constancy within a cell, colour differences provide a way to distinguish between neurons and thus could be useful for detailed circuit analysis, such as to count the number of neurons that innervate a postsynaptic cell.
Yes, we may now have a tool to map the wiring of the brain. This is a huge advance for neuroscience.
Jean Livet, Tamily A. Weissman, Hyuno Kang, Ryan W. Draft, Ju Lu, Robyn A. Bennis, Joshua R. Sanes & Jeff W. Lichtman
Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system
Nature (07) 450:56-62 doi:10.1038/nature06293