New insights on new neurons

Two studies on mice shed light on the role of neurogenesis in memory, olfactory sensing and antidepressant efficacy

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

In mice, new neurons are needed to remember mazes and keep their 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.

Newborn neurons (green, above) help mice build memories. Other research shows that antidepressants may help trigger neuron generation in the hippocampus.
NEWBORN NEURONS Underestimating the role of newborn neurons, such as these in an adult mouse hippocampus (green), has been difficult. Two new studies shed light on the question. Chunmei Zhao / Gage Lab / Salk Institute

Both studies are part of a new wave of research that shows neurogenesis — once thought to be impossible in the 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 didn’t know why it was necessary to make new cells in those brain regions.

Japanese researchers led by Ryoichiro Kageyama, a neuroscientist at KyotoUniversity, report August 31 in an advance online publication of 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 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 new olfactory bulb neurons seem to act like the adult stem cells that maintain skin, blood and gut, says Kageyama. 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 mice 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 memories, the researchers say. Blocking neurogenesis impaired mice’s ability to remember a maze for more than week, while mice with intact hippocampuses 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, 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.

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 Southwestern Medical Center at Dallas. But the research could shed light on why some people don’t respond to antidepressant therapy and 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,” he says. “We’re getting an idea of what molecules mediate this.”

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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