Watching the Brain Take a Sniff

A whiff of perfume or the smell of wood smoke can dredge up a host of memories. But to the brain, smells are simply mixtures of chemicals detected in the nose that need to be coded into a signal in order to get processed. In the July issue of Neuron, a team at Duke University Medical Center in Durham, North Carolina, describes a powerful new imaging tool that helps read the brain's "smell code."

Humans can smell so many different odors because they have over 1000 different receptor proteins on neurons in the nose, each of which recognizes a particular chemical feature of some odor molecules. The neurons send their signals to the brain's olfactory bulb, where each of thousands of little clusters of neurons called glomeruli receives input from olfactory neurons with just one receptor type. That means each smell should activate a unique pattern of glomeruli--the "code" for that smell. To find these patterns, researchers used to expose rats to an odor for 45 minutes--an unnaturally long time--then kill them and look for changes in the uptake by the olfactory bulb of a labeled form of glucose, which indicates neuronal activity. Duke neuroscientist Lawrence Katz and graduate student Benjamin Rubin set out to develop a more natural method that would allow them to expose a single animal to many odors at different concentrations and under various conditions.

They chose a technique called intrinsic signal imaging, which has been used for years on the visual system. Light reflected from a patch of brain surface of a living animal can reveal changes in blood oxygenation or in the light-scattering properties of neural membranes, both of which reflect changes in neural activity. Rubin tried the technique on rats, removing or thinning the part of the skull lying over their olfactory bulbs, then measuring the pattern of optical signals when the animals were exposed to different odors. It worked beautifully, says Katz, with a resolution "10-fold better than in the visual system." The researchers could clearly visualize individual glomeruli and saw each odor produce a unique pattern of active glomeruli.

"This is really a breakthrough," says Randolf Menzel of the Free University of Berlin, who studies olfaction in honeybees. He says the technique should offer neurobiologists many new opportunities to examine the ways the brain processes specific sensory information.