Probing the Workings of Hearts and Minds

Contrary to long-standing scientific dogma, the brain rises to a challenge by actually developing new neural cells in areas devoted to learning and memory--even in middle-aged minds, neuroscientists at the Salk Institute for Biological Studies reported Wednesday.

In a provocative glimpse into how the brain is shaped by the world around it, a team of Salk researchers in La Jolla led by Fred H. Gage now has demonstrated in laboratory animals that the right kind of mental gymnastics can dramatically increase the number of cells in a key region of the adult brain.

The researchers found that adult mice, left for several months to run in cages outfitted with toys, tunnels and exercise wheels, fed from a varied menu and sleeping on regularly changed bedding, developed up to 15% more neural cells than those housed in a less interesting environment.

The animals also performed much better than their less pampered siblings in mazes testing agility and intelligence. They appeared smarter--and learned more quickly.

“If these results are applicable to learning and mental development in humans,” Gage said, “they would suggest it is never too late.”

Teachers and parents know well that the brains of children, properly stimulated, flower in a burst of astonishing mental development as learning prompts the creation of trillions of neural connections.

Scientists long have been convinced that such flexibility does not affect the actual number of cells in the brain, just the complexity of the connections between them. Adult brains were thought to be, quite literally, set in their ways, limited to the neurons with which they began.

But the new findings, published today in Nature, suggest that “while exposure to stimuli in early childhood is certainly important, intellectual stimulation during life’s later years can still influence the architecture of your brain,” Gage said.

The results are hard evidence of the importance of the environment in mental development throughout life, several experts said. It reveals that the brains of mammals may be more physically impressionable than anyone had suspected.

“It is very exciting,” said William T. Greenough, an authority on the neurobiology of learning and memory at the University of Illinois.

“What this says is that you can add neurons and you can add system capacity” to the brain in response to experience, he said.

The work is the latest in a cascade of revolutionary insights into the way the brain works, based on advances in biophysics, molecular biology, neurochemistry and computer science.

As a result, researchers are gaining new respect for how the powerful stimulus of the outside world, guided by the action of genes, sculpts the brain’s 100 billion neurons into a working intelligence.

The Salk research focuses on a region of the brain, called the dentate gyrus of the hippocampus, considered critical to the development of memory.

For a number of years, researchers have known that area continued to produce precursors to brain cells well into adulthood, almost as if it were still in its embryonic state. Scientists have been anxious to learn what these mysterious cells do, how they may be affected by the environment around them and what biological forces could be at work.

Normally most of the new cells die off, but the Salk scientists determined that proper mental stimulation appears to increase the number of budding brain cells by enhancing their ability to survive and become functioning neurons.

Indeed, the extra stimulation caused an increase of 57% in the number of these precursor cells that became neurons. The end result was an extra 100,000 cells overall in each of the enriched animal brains under study--a 15% increase in the total number of cells.

“That was part of the surprise for us; not only was there an effect, but it occurred in adults and it was of such magnitude,” said Gage, who conducted the research with Gerd Kempermann and H. Georg Kuhn at the Salk Institute.

“We would have been surprised at one-tenth of that,” Gage said.

UC Berkeley researchers first noticed a relationship between an enriched environment and the number of brain cells in the hippocampus almost eight years ago, according to Marian Diamond, an expert at UC Berkeley on brain development.

“The general idea is exceedingly important,” Diamond said.

The current work at Salk makes use of more sophisticated technology to document how the increase in cells is greater than previously believed and to shed new light on just how stimulation and learning alter brain structure.

In the Salk study, closely related mice were raised together, then separated into the enriched or poor environments when they were 21 days old--a mouse age equivalent to that of a teenager. They stayed in their cages for 40 days, were tested, then returned to the cages for another 23 days. Finally, their brains were sampled to catalog and compare any changes.

Taking an accurate census of the new brain cells took “weeks and weeks” of computer time, Gage said.

Nonetheless, several experts were skeptical of the newest finding. “It is interesting but hardly surprising,” said Richard F. Thompson, head of the neurosciences program at USC.

Greenough and other experts cautioned that there is no evidence yet that such new neural cells may be forming in the adult human brain.

But Diamond was optimistic.

“I feel very confident to say that one would find it in humans as well,” she said.