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Watching Living Brains (video)
January 21, 2003

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Interviewees: Karel Svoboda, Cold Spring Harbor Laboratory; Wenbiao Gan; New York University School of Medicine.

Video is 1 min 34 sec long. Please be patient while it loads enough to start playing.

Produced by Brad Kloza

Copyright © ScienCentral, Inc., with additional images courtesy Karel Svoboda and Wenbiao Gan.

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For the first time, scientists can watch individual brain cells in living animals for long periods of time.

But as this ScienCentral News video reports, they've come to differenent conclusions about what it tells us about our brains.

A New Era in Neuroscience

How hard-wired is the brain? Is it like a computer, with circuitry that’s fixed in one place and stays there, or do brain cells continue to grow and change after the brain has reached a mature age?

One of the oldest questions in neuroscience could soon to be answered by a new technique that allows scientists for the first time to watch individual brain cells in a living animal—for up to several months. But the first two groups of neuroscientists using this technique came to different conclusions about the stability of the adult brain.

The journal Nature, which published the papers of both groups, says the technique “will have far-reaching implications for neurobiology.” The technique, called 2-photon laser scanning microscopy, uses infrared light rather than visible light. It allows imaging in animals, like a mice, that have been genetically modified to produce a fluorescent protein in a small subset of brain cells (neurons), which makes the neurons light up when the two photons infrared light hit them. Infrared light is key because neurons reside too deep in the brain for visible light to reach them, whereas infrared light can penetrate deeper.

“Looking at the [living] brain with traditional microscopy is like looking at a glass of milk,” says Karel Svoboda, neuroscientist at Cold Spring Harbor Laboratory. “So to illuminate the brain we use infrared light, which can penetrate this otherwise impenetrable tissue. And we can resolve synapses with this technique deep in the intact brain.”

Synapses are the connections between brain cells, and are so tiny that a thousand synapses could fit on the width of a hair. Other brain imaging techniques, like MRI, do not even come close to being this precise. Wenbiao Gan, neuroscientist at New York University Medical School and part of the second team that published its results in Nature, compared this revolution in brain science not to the microscope, but the telescope.

“You know, previously we could look at maybe the mountains on the moon,” he says. “But now we're able to look at the stones of those mountains of the moon.”

So what did they see?

Both teams set out to answer the question of how stable the adult brain’s connections are. Using 2-photon microscopy, the teams looked at specific, but separate, areas of the brains of mice for between one and four months.

Gan’s team looked at the visual cortex of the brains of mice at various ages for up to four months (which Gan says might compare to about 10 years in a human’s life). They found that while in adolescence the synaptic connections did change quite a bit. But by the time the mice reached adult age, synapses were 96 percent stable.

“Large proportions of connections can last for almost a lifetime,” he says. “So this would provide a physical basis for long term storage of information, or long term memory.”

Svoboda’s team looked at the barrel cortex—the area that deals with signals from the mouse’s whiskers—for a month. Contrary to Gan’s results, they found a great deal of change, or “plasticity,” even in the brains of adult mice. Beyond that, they claim to have found two distinct classes of synapses: those that are stable for long periods of time, and those that come and go in a matter of days.

A number of different variables might contribute to the discrepancy. Prominent among them is the fact that they looked at different areas of the brain. Svoboda says that the visual cortex tends to be stable while the part of the brain he studied, which deals with the whiskers, is known to be plastic because of all the learning it does through sensory experience.

In fact, Svoboda’s team took the extra step of watching the brain after clipping the mice’s whiskers. When a mouse had to learn how to explore their environments with altered whiskers, the rate of synaptic change increased a great deal.

“So the turnover of synapses is actually modulated by learning, and we'd like to make that connection even more clear,” he says. “To teach the animal something and look at the growth of synapses in response.”

Other variables that the scientists pointed out were the difference in exact age of the mice; the technique that was used to get access to look at the mouse brains; and the precise nature of the types of neurons they were looking at.

However, both scientists believe that a conclusion will be reached soon, perhaps within half a year. And both agree that proving this new technique is reliable and useful trumps any controversy that might exist between their results. A whole new world of research has just been opened up.

“We have to worry about not to work on too many things rather than having not enough to work on,” says Svoboda.

The work of the Gan team was funded by the National Institutes of Health, the Ellison Foundation, and an Irene Diamond grant. The work of the Svoboda team was funded by the Pew, Mathers, and Lehrman Foundations, the NIH, and the Howard Hughes Medical Institute.

by Brad Kloza

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