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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 thatâ€™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
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 brainâ€™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.
Ganâ€™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 humanâ€™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.”
Svobodaâ€™s team looked at the barrel cortex—the area that deals
with signals from the mouseâ€™s whiskers—for a month. Contrary to
Ganâ€™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, Svobodaâ€™s team took the extra step of watching the brain after
clipping the miceâ€™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
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.