Creating new nerve cells makes sense for the brain: neurogenesis seems to aid memory, depression drugs.

Most of the brain does fine with its original brain cells, but parts involved in smelling and remembering sometimes need new recruits.

In mice, new neurons are needed to remember mazes and keep scent-sensing organs plump (but aren't necessary for detecting smells), a new study shows. Another recent study demonstrates that some antidepressants require neurogenesis--the creation of fresh neurons--to work.

Both studies are part of a new wave of research that shows neurogenesis--once thought to be impossible in the adult brain--plays an important role in the organ's function.

"These are both very good papers and consistent with the growing appreciation for the importance of adult neurogenesis in general and in particular in behavior," says Fred "Rusty" Gage, a neuroscientist at the Salk Institute for Biological Studies in La Jolla, Calif.

Neurogenesis creates new neurons in the hippocampus, a part of the brain linked to learning and memory, and in the olfactory bulb, an organ that detects smells and pheromones. But scientists haven't known why it is necessary to make new cells in those brain regions.

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Now researchers led by Ryoichiro Kageyama, a neuroscientist at Kyoto University in Japan, report online August 31 in Nature Neuroscience that neurogenesis plays different roles in the two brain structures.

Nearly all of the cells in the olfactory bulb are replaced, and that regular refreshing of neurons is required to maintain the shape and volume of the bulb, the researchers report. But mice with shrunken olfactory bulbs had no trouble sniffing out sweet treats, suggesting that a few old neurons are all that's needed to maintain a sense of smell.

Neural stem cells that make the new olfactory bulb neurons seem to act like the adult stem cells that maintain skin, blood and gut, Kageyama says. But the researchers don't yet understand why a breakdown in maintenance doesn't destroy the mice's sense of smell.

"Smell is so important for mice that redundancy in olfaction could be intensive," Kageyama says. "It is also possible that the mice have some olfactory defect that we are so far not aware of." The team has not yet tested whether these mice, the ones with atrophied olfactory bulbs, can still detect pheromones.

In contrast to the olfactory bulb, far fewer new neurons are added to the hippocampus. More than 10 percent of neurons are replaced in the hippocampus, but their addition doesn't make the brain region bigger, and blocking neurogenesis doesn't make the hippocampus shrink, Kageyama and his colleagues found. There might be only a few new neurons, but they are important for mice to form new memories, the researchers say. Blocking neurogenesis impaired mice's ability to remember a maze for more than week, while mice with intact hippocampi remembered the maze two weeks after learning to run it.

"It's not a straightforward linkage between neurogenesis and memory," says Paul Frankland, a neuroscientist at the Hospital for Sick Children Research Institute in Toronto, Canada, who was not involved in the new studies. Memories can still form in the absence of neurogenesis but may be subtly different from those made when new neurons are present, he says. Neurogenesis may help form a timeline for memories, with new neurons helping to keep track of memories formed at the time the cells joined the hippocampus.

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Neurogenesis in the hippocampus slows down as mice age. Similar slowing in people could help explain why memory fails as people get older, Kageyama says.

Another mystery about neurogenesis concerns antidepressants known as selective serotonin reuptake inhibitors or SSRIs, the class of drug that includes Prozac. Those drugs were previously shown to stimulate neurogenesis in the hippocampus, but scientists were not sure if that was a side effect of the medication or necessary for its action.

Now, a study on mice in the Aug. 14 Neuron shows that neurogenesis in the hippocampus depends on the action of a protein called TRKB, and that neurogenesis is required for the antidepressant effects of SSRIs.

That doesn't mean that depression is caused by a defect in neurogenesis, says Luis Parada, who led the study with colleagues at the University of Texas South-western Medical Center at Dallas.

But the research could shed light on why some people don't respond to anti-depressant therapy and could lead to the development of new drugs to treat depression.

"There is exciting evidence that, in a variety of animal models, neurogenesis accompanies response to antidepressants," Parada says. "We're getting an idea of what molecules mediate this."

Back Story | OVERTURNING THE NEUROGENESIS DOGMA

1960s

Experiments on rhesus monkeys help cement a dogma that had been building for more than a century--no new neurons form in the adult brain. Scientists believed that people are born with all the neurons they will ever have.

1965

Joseph Altman and Gopal Das at MIT report the birth of new brain cells in the olfactory bulb and hippocampus of adult rats, casting some doubt on the dogma. But the researchers can't say for sure whether the new cells are neurons or support cells known as glia.

1980s

Canaries make new neurons when learning songs, and rats brains weigh more after learning to run a maze, researchers learn. These experiments suggest that new neurons are born in the adult brain, but most scientists cling to the old dogma.

1992

Elizabeth Gould publishes the first in a series of observations of neuro-genesis in the adult brain. Gould first saw the signs of newborn neurons in rat brains and later in marmosets.

1998

Peter Eriksson and Fred Gage show that adult human brains also make new neurons. Experiments by many researchers follow, but controversy lingers about where new neurons are made and why.

2000

Reports linking depression and neurogenesis in the hippocampus begin to appear. Scientists learn that increasing serotonin levels can stimulate the growth of new neurons, leading to the idea that enhancing neurogenesis could treat depression.

Neurogenesis in adult mouse brain.