Brainbow Mouse - a new way to map the brain's neuronal circuitry

Blogging on Peer-Reviewed ResearchIf 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:

i-5045641a131dd23aa18c45398276959c-brainbow.jpg

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.

i-dd26e4c0d5710bc0ba29dcc651accdc8-cover_nature.jpg
Wow.

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.

For more read Dan's entry at his new home at bitesize bio.

[Update]

Mo posted an entry on this work last week and Sparc has three different posts (see comments).

Ref:
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

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That is so beautiful! Both aesthetically and scientifically.

Tell that to the editors of the Scienceblogs Main Page who chose

I mean, a microscope is like a funny looking TV that you've got to get really close to in order to see something that, compared to real TV, is rather boring.

as the quote of the day.

Hey, a good anaphase is miles more entertaining than "The Biggest Bachelor" or "Dancing With A Millionaire" or "America's Next Crime Scene Investigation" or whatever other tripe is on!