The future of brain imaging

Enlarge Image



The Harvard University team used a combination of multiple fluorescent proteins to colour brain cells (neurons) up to 90 distinct colours.

Until now, fluorescent labelling has been able to produce just a handful of shades, the Nature report says.

The new method could aid research into the circuitry of the nervous system.

We have already used brainbow to take a first peek at the nervous system of mice, and we've observed some very interesting, and previously unrecognized, patterns of neuron arrangement

Professor Joshua Sanes

Harvard University

It is hoped it will enable scientists to gain a greater understanding of how brain wiring goes awry in many different diseases.

It could also potentially help track the development of the nervous system, and give new insight into the origins of brain disorders.

Researcher Dr Jeff Lichtman said: "In the same way that a television monitor mixes red, green, and blue to depict a wide array of colours, the combination of three or more fluorescent proteins in neurons can generate many different hues.

"There are few tools neuroscientists can use to tease out the wiring diagram of the nervous system.

"Brainbow should help us much better map out the brain and nervous system's complex tangle of neurons."

Gene mix-up

The brainbow technology uses a system for mixing up genetic material known as Cre/lox in a new way to shuffle genes encoding green, yellow, orange, and red fluorescent proteins.

Each time the system was used it produced a different pattern of genes, which then produced a wide range of colours when the material was inserted into individual neurons.

Dr Jean Livet, who also worked on the study, said: "The technique drives the cell to switch on fluorescent protein genes in neurons more or less at random.

"You can think of brainbow almost like a slot machine in its generation of random outcomes, and Cre/lox is the hand pulling the lever over and over again."

The researchers used brainbow to examine neural circuits in mice over a period as long as 50 days.

'Scratching the surface'

Professor Joshua Sanes, another member of the research team, said: "We have already used brainbow to take a first peek at the nervous system of mice, and we've observed some very interesting, and previously unrecognized, patterns of neuron arrangement."

But he added: "As far as understanding what we're seeing, we've only just scratched the surface."

Professor Ian Thompson, from the Medical Research Council's Centre for Developmental Neurobiology at King's College London, said the new method gave a much clearer way of identifying not only individual neurons, but also the connections they make with other nerve cells.

Potentially this could be of great help in monitoring the recovery of the brain from a stroke, for instance.

He said: "Most of the circuitry of the nervous system has been worked out by looking at one or two cells at a time, and building up from there.

"This gives us the possibility of looking at whole populations of cells at the same time."