April 25, 2000 'Rewired' Ferrets Overturn Theories of Brain Growth By SANDRA BLAKESLEE
Like inventive electricians rewiring a house, scientists at the Massachusetts Institute of Technology have reconfigured newborn ferret brains so that the animals' eyes are hooked up to brain regions where hearing normally develops.
The surprising result is that the ferrets develop fully functioning visual pathways in the auditory portions of their brains.
In other words, they see the world with brain tissue that was only thought capable of hearing sounds.
The findings, reported by Dr. Mriganka Sur and his colleagues in the April 20 issue of Nature magazine, contradict popular theories on how animal brains develop specialized regions for seeing, hearing, sensing touch and, in humans, generating language and emotional states.
Many scientists claim that genes operating before birth create these specialized 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 regions are not set in stone at birth.
Rather, they develop specialized functions based on the kind of information flowing into them after birth.
"Some scientists are going to have a hard time believing these experiments," said Dr. Jon Kaas, a professor of psychology at Vanderbilt University in Nashville. They demonstrate, Dr. Kaas said, "that the cortex can develop in all sorts of directions."
"It's just waiting for signals from the environment and will wire itself according to the input it gets," he said.
The findings may shed light on unusual brain patterns observed in people who are born deaf or blind, he added.
"If you wanted to create a dream experiment, this would be it," said Dr. Michael 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 process known as plasticity. "It's about the most compelling demonstration you could have that experience shapes the brain."
The researchers are all members or former members of the department of brain and cognitive sciences at M.I.T. The rewiring experiments began more than 10 years 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 station called the thalamus before reaching areas in the higher brain or cortex where vision and hearing are perceived.
In humans, this very basic wiring is present at birth, but in ferrets, these important nerves grow into the thalamus after the animal is born. Dr. Sur found that if he stopped the auditory nerve from entering the thalamus, the optic nerve would arrive a few days later and make a double connection. It would go on through 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 the 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 become 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 others 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 resembles 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 pinwheel 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, Dr. Sur said, but looked as if it might be functional.
The researchers then asked, What does the rewired ferret experience? Does it see 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 in 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 animals still responded to the light. It meant that they were seeing lights with their rewired auditory cortex, Dr. Sur said.
The research reopens the question of what are the relative contributions of genes 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 from the outside world that it becomes the seeing part of the brain. All the newborn cortex knows about the outside world is from the electrical activity of these 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 functional 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 stabilized. 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, children who suffer from a severe form of epilepsy that is treatable only by removing one-half of their brains can learn to walk, talk, throw balls and otherwise develop normally with only half a brain, if operated on early in life, he said.
But in recent years, scientists are also discovering that adult brains, as well, can undergo surprising changes in response to experience. For example, imaging experiments carried out on blind people show that when they learn to read Braille, "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 who 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 these 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 strokes, accidents and various brain diseases. http://www.nytimes.com/library/national/science/042500sci-animal-ferret.html