No New Neurons for Smell?

Do our brains continue to produce neurons throughout our lifetimes? That's been one of the most hotly debated questions in the annals of science. Since the 1950s, studies have hinted at the possibility, but not until the late 1990s did research prove that the birth of new neurons, called neurogenesis, goes on in the brains of adult primates and humans. Now a surprising new study in humans shows that in the olfactory bulb—the interface between the nose and the brain and an area long known to be a hot spot of neurogenesis—new neurons may be born but not survive. The finding may rule out neurogenesis in this area, or it might show only that some people don't stimulate their brains enough through the sense of smell, some researchers say.

Previous studies have found evidence of neurogenesis in the olfactory bulb of adult humans. But those studies measured only proteins produced by immature neurons, leaving open the question of whether these youngsters ever grew up to connect with other cells to form functional networks, says neuroscientist Jonas Frisén of the Karolinska Institute in Stockholm. If new olfactory neurons really reached adulthood throughout a person's life, researchers should find neurons of a variety of ages in this region.

That's not what Frisén and his team saw. The discovery is based on a technique he and his colleague Kirsty Spalding hit upon in 2005, in which they found a clever way to deduce the age of neurons. The method relies on atomic testing carried out in the 1950s and 1960s, which released massive amounts of carbon-14 into the atmosphere; the atmospheric 14C has been steadily declining ever since. Thus, the later a cell is born after this testing, the less 14C it contains.

In the new study, published this week in Neuron, Frisén, Spalding, and colleagues measured levels of 14C in olfactory bulb tissue taken during autopsy from the brains of 15 subjects who were born either before or after the atomic testing period. The researchers found that the neurons in the olfactory bulb were all the same age: the age of the individual they came from. "[That's] evidence that in humans, in this area, neurogenesis doesn't occur," says Frisén.

The finding may mean that as humans evolved from animals, we lost the ability to produce new neurons in this area because we don't rely as much on our sense of smell. On the other hand, it may mean that people living in an affluent, Western city like Stockholm aren't exposed to enough new smells to keep the neurons alive.

Neurobiologist Jeffrey Macklis of Harvard University says the study, though elegant and rigorous, doesn't settle this question quite yet. Macklis's lab and others have found that in mice, newly born neurons play a unique role in learning novel odors and die unless they are activated by new, unfamiliar smells. Because people depend less than rodents on the sense of smell, we might have comparatively less of these neurons to begin with, Macklis says. And what few we do create may not survive, because we aren't exposed to the same number of smells as other animals. "In affluent, Westernized areas, we shower every day; we use deodorant, air fresheners. We go out of our way to make sure that the only smells we're exposed to are the ones we know," Macklis says.

Macklis adds that the absence of neurogenesis in the brain tissue studied doesn't rule out the possibility in other groups of people. Many of the tissue samples, obtained from the Department of Forensic Medicine at the Karolinska Institute, came from donors with a history of substance abuse or psychiatric illness—both of which have been shown to decrease neurogenesis, as the authors note in the paper. So the fact that few new olfactory neurons were found in this group doesn't mean that such cells aren't flourishing in healthy people constantly exposed to new scents-chefs, sommeliers, perfumers, or travelers to exotic locales, Mackils says.

Neuroscientist Fred Gage of The Salk Institute in San Diego, California, agrees that the population studied may not be the best one. Gage, who first reported evidence of neurogenesis in the human brain, says the decrease in neurogenesis may show that as animals evolved from quadrupeds to primates to humans, the sense of smell became less important for survival.

Correction, 31 May: The original version of this article stated that the study donors died at the Karolinska Institute, and it attributed this statement to Jeffrey Macklis. Neither the statement nor the attribution were correct. Macklis did not make this statement, and the tissue was obtained from donors admitted to the Department of Forensic Medicine at the Karolinska Institute in Stockholm for autopsy. These errors were introduced by the staff of Science during the editing process. Macklis originally indicated that the donors had a range of premortem diagnoses: some were normal accident victims and some had clinical diagnoses as noted in the original paper. The donors were representative of a range of typical Swedish residents. We have corrected the seventh paragraph to address these errors.

Posted in Plants & Animals, Brain & Behavior