The old dogma that the adult human brain cannot generate new neurons was overthrown almost 10 years ago, but a question persists: do those new neurons do any good?

In 1998 scientists led by Fred (Rusty) Gage of the Salk Institute for Biological Sciences discovered that older adults "well into their 50s, 60s and even 70s "continue to produce new neurons in their brains. Last November, a study found that as little as three hours a week of brisk walking increases blood flow to the brain and increases production of new neurons, researchers reported in the Journal of Gerontology: Medical Sciences. The same team, led by Arthur Kramer of the University of Illinois, had earlier shown that older adults who engage in physical activity have better working memory, are more adept at switching between mental tasks (a skill that generally declines with age), and are better able to screen out distractions (ditto) compared to people of the same age who did not get exercise training. The obvious question arose: is the reason exercise improves cognitive function in older adults that it boosts "neurogenesis," the production of new brain neurons?

For more than a decade the study of neurogenesis has toggled back and forth between studies of lab animals and studies of people, with results in one shedding light on results in the other and inspiring the next series of experiments. Kramer's November study found that three hours a week of aerobic exercise increased the human brain's volume of gray matter (neurons) and white matter (connections between neurons), so much so that the exercisers had brain volumes typical of people three years younger. Gray matter increased most in the frontal lobes, which handles high-level functions such as planning, judgment, attention and memory. White matter increased most in the bundle of neurons that connects the right brain and the left.

Meanwhile, back on the lab-animal front, Gage's lab has been pumping out studies showing that when lab mice regularly go for a spin in the running wheel, their rate of neurogenesis increases and connections among neurons multiply and grow longer. Now he has zeroed in on where those new neurons go, shedding light on the role they play in the brain. New neurons, the Salk scientists report today in online edition of Nature Neuroscience, make a beeline for mature brain cells with lots of robust connections to other neurons, muscling out the old guys. "Adding new neurons could be a very problematic process if newborn cells [made] connections all over the place," Gage says. "But if they are only replacing already existing connections there is less chance of error."

That possibility had been why neuroscientists long held that the adult brain would never do something as dumb as make new neurons. Throwing a bunch of new cells into an already-wired brain would be as detrimental as throwing a few computer chips onto your motherboard, they assumed: the chance that they would make beneficial, functional connections was much less than the chance that they would muck things up. The new results show that this does not happen. Instead, by homing in on well-established existing connections, the Salk scientists found, new neurons in mouse brains replace obsolete or unreliable components. (They tracked the new neurons by using a virus to slip a green fluorescent protein into them.) "If you have hopes that one day neuronal stem cells can replace damaged neurons in neurodegenerative diseases such as Alzheimer's or Parkinson's disease you have to ensure that these cells make proper connections, form functional synapses and integrate into the rest of the brain," says Salk's Nicolas Toni. The mouse brain, at least, does just that.

Only half the newborn neurons managed to take their place in existing brain circuits "when the mice lived in bare, boring cages. But when the mice lived in larger cages with running wheels, colored tunnels and playmates, the percentage of new neurons that slid into (and presumably strengthened) existing brain networks rose to 80 percent. That brings us full circle to the 2006 results on the cognitive benefits of aging: aerobic exercise not only boosts the rate at which the human brain makes new neurons, but also (in mice) makes more of them find a home that should be of benefit to the brain. Yet more proof that exercising the body can rejuvenate the mind.