Jay Gottfried

Picky proboscis.
Painful shocks teach the human nose to distinguish between two similar smells.

The (Shocked) Nose Knows

Although they're staples of popular culture, Pavlov's dogs have nothing on the human nose. Scientists have shown for the first time that people can quickly learn to distinguish between almost identical smells if choosing incorrectly nets them a nasty shock. The result raises new questions about how emotional experiences affect our sense of smell and the role they play in sensory and anxiety disorders.

In the 1890s, Russian physiologist Ivan Pavlov trained dogs to associate a cue--usually a sound, such as a whistle or a bell ringing--with food. Eventually, the dogs would drool when they heard the cue, even if no food followed. From Pavlov on, many studies have looked at how experiences can shape responses--how shocks help a rat learn its way through a maze, for example. A 2005 study showed that conditioning can even change people's opinion of what they perceive: Smelling an unfamiliar odor while playing a frustrating video game provoked a dislike of the scent. But neurologist Wen Li of Northwestern University's Feinberg School of Medicine in Chicago, Illinois, and her colleagues wanted to determine if experience can change how well a person perceives a specific odor.

To answer that question, the team asked 12 subjects to distinguish two pairs of subtly different smells: a rose oxide molecule and its chemical mirror image--both of which have an almost identical "oily" smell--and a mirror pair of butanol molecules that share a vaguely plantlike aroma. An MRI scanned the smell centers of their brains as the subjects sniffed, and a slight electric shock accompanied one of the smells. Although the subjects couldn't distinguish any of the molecules from their mirror images before the shock, almost all could after fewer than seven jolts, the team reports online today in Science. Their brains also responded differently to each smell in the pair that included the shock, while their sensitivity and brain response to the other pair didn't change.

"We were fascinated" by how sharp the subjects' sense of smell became, says Jay Gottfried, an olfactory neurologist on Li's team. "The human sense of smell is always dissed, … [but] this shows it has tremendous capacity" to adapt in ways that likely helped human ancestors know when they were safe and when they should flee--for example, when distinguishing a lion's smell from a small cat's. Gottfried hypothesizes that a version of this reaction could be partly responsible for the heightened sensitivities of patients with anxiety disorders, phobias, and post-traumatic stress disorder, which often develop following an accident, a violent attack, or other ordeal.

The result doesn't just vindicate our sense of smell, says chemosensory researcher William Cain of the University of California, San Diego. It's also the first to document that conditioning can hone the human nose and alter the brain--and that is "pretty major stuff." Cain treats patients with multiple chemical sensitivities--a controversial condition in which people show unusual sensitivity to low levels of chemicals--and points to the study's results as a possible gateway to new treatments for their symptoms.

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