Researchers Reveal New Secrets of the Brain

By peering through a window into the brains of living mice, researchers Cold Spring Harbor Laboratory have caught a groundbreaking glimpse of adult brain cells forming new connections. Their study upends the long-held tenet that the structure of adult brains is fixed, sheds light on processes that underlie learning and memory, and offers hope for future treatment of brain trauma and mental retardation.

In a paper in the December 19 issue of Nature, neurobiologist Karel Svoboda and his colleagues present the most convincing evidence to date that the adult brain can rewire itself in response to outside world. While many neuroscientists had begun to speculate that adult brains might be more dynamic than once thought, neuroscience orthodoxy still held that adult brains are relatively stable, limiting learning and recovery from injury. Svoboda's team employed state of the art technology to show that new connections, called synapses, form and dissolve in the adult brain as the mice take in sensory information.

"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 Stony Brook University. "Namely, to show that, in a relatively short period of time, synapses grow in an adult brain."

The scientists created transgenic mice with neurons that expressed a fluorescent green protein. Then, they placed a small window over the part of the brain they wanted to study--the barrel cortex, a region associated with receiving information the mice gather with their whiskers. Every 24 hours for eight days and less frequently for the rest of a month, they checked to see which neurons sent out and retracted spines to form and eliminate connections with other neurons. To see if the changing connections were influenced by sensory input they cut every other whisker on the mice, creating a chessboard pattern in which each cut whisker was surrounded by uncut whiskers, and then let the mice explore an unfamiliar environment.

They found that the total number of synapses stayed relatively constant but the individual connections often changed. Some stuck around for only a few days and others, generally the thicker ones, stayed for the duration of the experiment. Significantly, connections formed and dissolved much more rapidly after the animals's whiskers were cut and the mice were placed in the novel environment, suggesting that the synapses changed according to new sensory input.

The Svoboda team theorizes that cells might reach out to each other, possibly randomly forming synapses which are then tested through experience--those that are useful are reinforced, growing stronger, while those that aren't wither away. Right now, however, the theory is pure speculation. Next, they hope to test whether synapses that are used more grow stronger.

Adult brains may forge new connections, but they are not nearly as malleable as developing brains, says Svoboda. His 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, however, the framework changes along with the synapses.

The research will likely pave the way for a host of other experiments looking for similar phenomena in other regions of the brain associated with different types of learning, said Murray Sherman, also a neurobiologist at Stony Brook University. Such studies should reveal something about the underlying mechanisms in degenerative diseases such as Alzheimer's and Parkinson's.