What A Beautiful Brainbow

The image at the top of this blog may look like a colourful piece of modern art, and, in a way, it is; but it’s not a painting, it’s a photograph of a slice of rodent brain prepared with a very special technique, aptly named brainbow.

Brainbow was developed at Harvard University and described by Jean Livet et al in the journal Nature (2007). The purpose of this research is to find ways of labelling multiple neurons (brain cells) at once in a way that allows them to be distinguished from one another in slices of brain tissue.

The technique works by using a number of genetic manipulations that cause fluorescent proteins to be produced in cells in a specific region of the brain. Fluorescent proteins have been used to mark cells for a number of years, and techniques that allow these proteins to only be made in specific regions of the body have also been available for some time. Previously, however, all of the cells in a region would fluoresce with the same colour, making it very difficult, even impossible, to track any one cell. With this technique, the researchers have used multiple genes that produce different colours of fluorescent protein and  a genetic modification technique known as Cre/lox recombination. Again, the Cre/lox system has been around for some time but by using it in conjunction with multiple fluorescent protein genes, the researchers are able to create a scenario where the colour that any given cell presents is determined in a random manner. This means that adjacent cells in the same region can be marked with different colours.

This image shows the possible outcomes for a cell that contains the DNA illustrated in the top panel. In this scenario the blue and red genes are paired and the green and yellow genes are paired. In the cell containing this, one pair will be removed and the remaining pair may or may not be flipped. Only the gene in the correct orientation will produce protein so in this way, one of the 4 colours is randomly selected to be made.

Furthermore, multiple copies of the genetic material can be expressed in a cell, meaning that one cell can be making fluorescent proteins of different colours. This provides even more possible colours of cell. In their experiment, the researchers found 90 different cell colours when originally only using a few different colours of fluorescent protein.

Many different cell colours can come from just 3 initial protein colours

Apart from creating beautiful images,  the hope is that this technique can be used to map the connections that cells make and better understand the role of certain cells and the interaction of cells.

Links:

http://cbs.fas.harvard.edu/science/connectome-project/brainbow

Lichtman, J.W et al. (2008), Nature Reviews Neuroscience 9, 417-422

Livet, J et al. (2007), Nature 450, 56-62

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