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Friday, Jan. 3, 2003
The mice with the windows in their skulls
Peering into the brain has been the dream of scientists for years -- now it's reality
By ROWAN HOOPER
The British entertainer Derren Brown has caused a stir by apparently demonstrating mind control. He's not psychic, he says, but he can see into other people's brains.
"Once you understand someone else's perception of a situation," he said, "you can mentally exist inside their heads."
Of course, Brown cannot literally see into other people's brains. That would be a truly unbelievable claim, no matter how remarkable his talent. However, seeing into brains is precisely what scientists from the United States and Switzerland have recently managed to do. The neurobiologists technological breakthroughs have allowed them to see though a window into the brains of living mice, and view individual neurons in the cerebral cortex.
"If a few years ago you could have imagined in your wildest dreams the experiment you wanted to do, it would be this one," said Paul Adams, a neurobiologist at the State University of New York, Stony Brook, not connected with the new work. "To show that, in a relatively short period of time, synapses grow in an adult brain."
Neurobiology has had a long-held tenet that while the structure of the brain is flexible and changeable during childhood, it becomes fixed by adulthood. We all know that we can learn new things as adults and form new memories, but neurobiologists have always said that this cannot be due to physical changes in the structure of our brains.
That view has now been overturned by the new work, which has shown that the adult mammalian brain can rewire itself in response to stimulation from the outside world. There may be implications for future treatments of brain trauma and mental retardation and the research sheds light on processes that underlie learning and memory.
The scientists created transgenic mice with neurons that expressed a fluorescent green protein. Then they removed part of the skull over the area of the brain they wanted to study (the barrel cortex, a region associated with receiving information the mice gather with their whiskers) and installed a tiny glass window.
Every 24 hours for eight days and less frequently for the remainder of a month, the team, led by Karel Svoboda of the Cold Spring Harbor Laboratory, N.Y., checked what was going on in the brains of the mice. They were interested in neuronal spines. Nerve cells (neurons) have long, thin extensions called dendrites, and on these dendrites are tiny protrusions called neuronal spines. Spines form the essential part of the synapse, the connection that mediates signaling between neurons.
Scientists believe that spines are the basic functional unit in the brain. There are around 10,000 spines per neuron and there are tens of billions of neurons in an adult human brain, which gives an indication of how we are able to store and process so many memories.
Usually, scientists have to kill mice to study their neuronal spines, but by creating mice with fluorescent neurons, the researchers could see what happened to the spines and the synapses in living animals. They tested whether sensory input would change the neural connections by cutting every other whisker on the mice, creating a chessboard pattern in which each cut whisker was surrounded by uncut whiskers. The mice were then allowed to explore an unfamiliar environment.
Svoboda and colleagues found that the total number of synapses in the mice stayed relatively constant, but the individual connections often changed. Some were stable for only a few days and others, generally the thicker ones, stayed for the duration of the experiment.
An important finding was that connections formed and dissolved much more rapidly after the animals' whiskers were cut and they were placed in the novel environment. This suggests that the synapses changed according to new sensory input.
The Svoboda team, writing in a recent issue of Nature, theorizes that cells might reach out to each other, perhaps even randomly. Synapses which are so formed are then tested through experience: those that are useful are reinforced, growing thicker, while those that aren't wither away.
Right now, however, that theory is only speculation. Indeed, a paper in the same issue of Nature by Jaime Grutzendler and colleagues from the department of physiology and neuroscience at New York University School of Medicine reported that most of the spines they looked at remained stable for over a month.
Adult brains may forge new connections, but they are not nearly as malleable as developing brains, says Svoboda. His team's study hints that while adult neurons form and eliminate synapses between cells in their general vicinity, the large-scale organization of brain cells doesn't really change. In developing brains the entire framework changes along with the synapses.
Much remains to be clarified; our view of how brains work and how memories are stored is far from complete. However, the ability to watch neurons grow in living brains is a research tool that will revolutionize experimental neuroscience and the study of learning. In the future this ability should clarify the underlying mechanisms in degenerative diseases such as Alzheimer's and Parkinson's.
Rowan Hooper welcomes comments at firstname.lastname@example.org