Somewhere Over the Brainbow

in Article, News
March 9th, 2011

Because of the brain’s amazing and incomprehensible complexity, there are billions of neurons that connect and network all the major areas of the brain with the small intricate parts as well. So how can we distinguish one of these neurons from the billions of others?

Well, within the past five years more advanced techniques have been discovered and used on various organisms. The most prevalent, and probably the most revolutionary, has been staining. This process was pioneered in the late nineteenth century by Camillo Golgi and allowed for the staining of whole, random cells.

Since then, much progress has been made and today the viewing of even more complex and minute parts that make up the brain is possible. One extraordinary technique was developed by a team of Harvard researchers a few years ago, and it is truly beautiful.

Known as the Brainbow technique, these investigators were able to use genetics to visualize complete neuronal circuits in unprecedented detail. Up to four differently colored fluorescent proteins were used, generating  a palette of 100 distinct hues that labeled individual neurons.

/Here are the fluorescent proteins in their full glory illuminating the many neurons that make up the brain of a mouse.

This technique was developed with the use of the Cre/loxP site-specific recombination system, a sophisticated method that is commonly used to generate mutant mice lacking a specific gene. Basically, this recombination inverts parts of the DNA sequence at specific sites along the genome. The mating of two different mice strands allows for recombination.

Fluorescent proteins were added to certain constructs of cells, all of which were able to emit colors such as red, cyan, yellow, and green. Multiple copies of the constructs were integrated into a stem cell chromosome, and many random combinations of these four genes were then expressed.

Confocal microscopy was used next to generate three-dimensional reconstructions that traced the multi-color palette onto complete neuronal circuits in various regions of the brain. Thanks to this incredible new technique, a large number of neurons and the connections between them have been labelled and led to new systems based on this discovery.

Since its discovery, the Brainbow technique has allowed for unprecedented visualization of neurons and neuronal circuit in many classic model animals, such as the fruit fly and mouse. Hopefully one day, techniques such as this will aide us in our attempt to untangle the interconnections of our own brains and allow us to further appreciate its beautiful intricacies.

The 100 Colours of the Brainbow: Neurophilosophy

Harvard Researchers Illuminate Connections Among Brain Cells in Technicolor -Popular Science

Transgenic Strategies for Combinatorial Expression of Fluorescent Proteins in the Nervous System: Article – Nature

Colorful Images to Help Illuminate the Brain –

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