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 Writing in the journal Nature, they unveiled the mouse
'connectome,' a map showing the sinuous connections that neurons
make throughout the mouse brain as they form functional circuits.
The mouse connectome "provides the most detailed analysis of brain
circuitry currently available for any mammalian brain," said
neuroscientist David Van Essen of Washington University in St.
Louis, co-leader of the human connectome project, which aims to do
that for Homo sapiens. "It is truly a landmark study."
A connectome is essentially a wiring diagram. It shows how each of
the millions or billions of neurons (gray matter) in a brain each
connect to thousands of other neurons through projections called
axons, the white matter, and thereby allow brain regions to
communicate to produce behavior, intelligence, and personality.
Such a diagram could reveal, say, how neurons that register the
taste of a cookie fan out to circuits that store memories and
unleash a torrent of remembrances of things past. And it could
reveal what causes those circuits to malfunction in diseases such as
Alzheimer's.
Before the mouse, the only species for which scientists had created
an essentially complete connectome was the roundworm C. elegans. It
has 302 neurons.
The human brain has some 86 billion, each making as many as 10,000
connections.
GLOWING NEURONS
For the mouse connectome, scientists led by Hongkui Zeng of the
Allen Institute for Brain Science in Seattle, Washington, used some
of the 21st-century techniques that are required to create a human
connectome. For the mouse, the key was to make neuronal connections
literally shine.
To do that, Zeng's team injected viruses into precise spots in the
brains of living mice. The viruses produce a special protein that
fluoresces green. When the glowing protein diffuses throughout the
neurons and their axons, the circuits show up under a microscope
after the mouse is killed and its brain sliced.
Out of 295 distinct structures in the mouse brain, the technique
revealed the neuronal highways into and out of all but 18. Many of
the missing ones are tiny structures close to the bottom of the
brain which are hard to hit with the virus.
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The map revealed several surprises about brain wiring. Connections
that stay on one side of the brain "seem to be always stronger" than
those that cross hemispheres, Zeng said.
The mouse's neuronal connections also vary widely in strength. That
"must be contributing to brain network computation," she said. "We
think a small number of strong connections and a large number of
weak connections may be a fundamental network organization property
to allow greater capacity of information processing."
The mouse connectome unveiled on Wednesday is a medium-scale map,
showing long-range and local connections. It does not have the
resolution to reveal the precise neuron-to-neuron connections, or
synapses, as a "microscale" connectome would, though that is a goal.
A large-scale map is the goal of the Human Connectome Project, which
the National Institutes of Health announced in 2010 and which Van
Essen calls "one of the great scientific challenges of the 21st
century." It is being produced using special technique called
diffusion tensor imaging in living brains.
The human connectome will resemble the Human Genome Project in a key
way. Just as the genome project discovered the precise sequence of
three billion molecules common to the vast majority of humans' DNA,
serving as a reference book against which to measure individual
genetic differences, so the connectome will first reveal
neuro-commonalities and, eventually, the uniqueness of each
individual brain.
(Reporting by Sharon Begley; editing by Julie Steenhuysen and James
Dalgleish)
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