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http://web.mit.edu/msur/www/nytimes.html

NY Times April 25, 2000

'Rewired' Ferrets Overturn Theories of Brain Growth

By SANDRA BLAKESLEE


Like inventive electricians rewiring a house, scientists at the Massachusetts I
nstitute of Technology have reconfigured newborn ferret brains so that the anim
als' eyes are hooked up to brain regions where hearing normally develops.
The surprising result is that the ferrets develop fully functioning visual path
ways in the auditory portions of their brains.

In other words, they see the world with brain tissue that was only thought capa
ble of hearing sounds.

The findings, reported by Dr. Mriganka Sur and his colleagues in the April 20 i
ssue of Nature magazine, contradict popular theories on how animal brains devel
op specialized regions for seeing, hearing, sensing touch and, in humans, gener
ating language and emotional states.

Many scientists claim that genes operating before birth create these specialize
d regions or modules, arguing for example that the visual cortex is destined to
 process vision and little else. But the ferret experiments show that brain reg
ions are not set in stone at birth.

Rather, they develop specialized functions based on the kind of information flo
wing into them after birth.

"Some scientists are going to have a hard time believing these experiments," sa
id Dr. Jon Kaas, a professor of psychology at Vanderbilt University in Nashvill
e. They demonstrate, Dr. Kaas said, "that the cortex can develop in all sorts o
f directions."

"It's just waiting for signals from the environment and will wire itself accord
ing to the input it gets," he said.

The findings may shed light on unusual brain patterns observed in people who ar
e born deaf or blind, he added.

"If you wanted to create a dream experiment, this would be it," said Dr. Michae
l Merzenich, a neuroscientist at the University of California at San Francisco
and a leading authority on the brain's ability to change and reorganize, a proc
ess known as plasticity. "It's about the most compelling demonstration you coul
d have that experience shapes the brain."

The researchers are all members or former members of the department of brain an
d cognitive sciences at M.I.T. The rewiring experiments began more than 10 year
s ago, Dr. Sur said. He chose ferrets because their brains are very immature at
 birth and undergo a late form of development that the researchers can exploit.


As in humans, the ferret's optic and auditory nerves travel through a way stati
on called the thalamus before reaching areas in the higher brain or cortex wher
e vision and hearing are perceived.

In humans, this very basic wiring is present at birth, but in ferrets, these im
portant nerves grow into the thalamus after the animal is born. Dr. Sur found t
hat if he stopped the auditory nerve from entering the thalamus, the optic nerv
e would arrive a few days later and make a double connection. It would go on th
rough the thalamus and connect itself up to both seeing and hearing regions of
the cortex.

The researchers then waited to see what would happen to the hearing region of t
he brain once it was getting all its signals from the retina.

After a ferret or human is born, cells in the brain's primary visual area becom
e highly specialized for analyzing the orientation of lines found in images or
shapes. Some cells fire only in response to vertical lines. If presented with a
 horizontal or slanted line, they don't do anything.

Other cells fire exclusively when a horizontal line falls on them and yet other
s fire in response to lines slanted at various angles. These specialized cells
are draped across the primary visual area in a somewhat splotchy fashion that r
esembles a bunch of pinwheels.

The hearing region of the brain is organized very differently, Dr. Sur said.

Each cell is connected to the next in a kind of single line. There are no pinwh
eel shapes.

After the rewired ferrets matured, researchers looked at the auditory region of
 their brains and found that cells were organized pinwheel fashion. They found
horizontal connections between cells responding to similar orientations.

The rewired map was less orderly than the maps found in normal visual cortex, D
r. Sur said, but looked as if it might be functional.

The researchers then asked, What does the rewired ferret experience? Does it se
e or does it hear with its auditory cortex?

Rewired ferrets were trained to turn their heads one way if they heard a sound
and in the other direction if they saw a flash of light. In these experiments,
one hemisphere was rewired and the other was left normal as a control. Thus the
 animals could always hear with the intact side of their brains and were deaf i
n the rewired side.

Not surprisingly, when the light was presented to the rewired side, the animals
 responded correctly.

But when connections to visual areas were severed on the rewired side, the anim
als still responded to the light. It meant that they were seeing lights with th
eir rewired auditory cortex, Dr. Sur said.

The research reopens the question of what are the relative contributions of gen
es and experience in building brain structure, according to Dr. Kaas.

Genes, Dr. Kaas suggests, create a basic scaffold but not much structure.

Thus, in a normal human brain, the optic nerve is an inborn scaffold connected
to the primary visual area. But it is only after images pour into this area fro
m the outside world that it becomes the seeing part of the brain. All the newbo
rn cortex knows about the outside world is from the electrical activity of thes
e inputs, or images that fall on the retina, sounds that reach the inner ear or
 touch sensations that press on the skin, Dr. Kaas said.

As the inputs arrive, the cells organize themselves into circuits and functiona
l regions.

As these circuits grow larger and more complex, Dr. Kaas said, they become less
 malleable and, probably with the help of changes in neurochemistry, become sta
bilized. This is why a mature brain is less able to recover from injury than a
very young brain.

Young brains are astonishingly plastic, Dr. Kaas said. For example, he said, ch
ildren who suffer from a severe form of epilepsy that is treatable only by remo
ving one-half of their brains can learn to walk, talk, throw balls and otherwis
e develop normally with only half a brain, if operated on early in life, he sai
d.


But in recent years, scientists are also discovering that adult brains, as well
, can undergo surprising changes in response to experience. For example, imagin
g experiments carried out on blind people show that when they learn to read Bra
ille, "visual" areas of their brains light up.

Touch seems to be residing in visual areas. Similar experiments on deaf people
show that they use the auditory cortex to read sign language, whereas people wh
o can hear use the visual areas of the brain for this purpose.

Dr. Sur said his laboratory was now searching for molecules that help produce t
hese kinds of changes in mature and developing brains.

If the chemistry of regrowth and reorganization can be understood, he said, it
would offer new avenues for helping people recover from damage caused by stroke
s, accidents and various brain diseases.



Copyright 2000 The New York Times Company



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