NEUROBIOLOGY: Mapping Smells in the Brain

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http://ep.llnl.gov/msds/ScanDbase/Smell-map-Sci-99.h

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Science, Volume 285, Number 5427 Issue of 23 Jul 1999, p 508
©1999 by The American Association for

the Advancement of Science.

NEUROBIOLOGY:
Mapping Smells in the Brain
Marcia Barinaga
A whiff of perfume or

the smell of wood smoke may dredge up complex memories, but every smell starts as a simple code. Now, a team at Duke

University Medical Center in Durham, North Carolina, has developed a powerful new tool for reading the brain's

smell code.

Each sensory system has a code for the information it receives. For example, hearing uses a

frequency code, while the olfactory system encodes odors by chemical composition. There are over 1000 different

olfactory receptor proteins found 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.

Researchers want to

know how the brain uses that code to process olfactory information further, and now Duke neuroscientist Lawrence

Katz and graduate student Benjamin Rubin have developed an essential tool for doing so. In the July issue of Neuron

they report that they have used an optical imaging technique to see the patterns of glomeruli that respond to

particular odors in rat brains--the first time that's been done in living mammals.

"This is really a

breakthrough," says Randolf Menzel of the Free University of Berlin, who studies olfaction in honeybees. He and

others note that because the olfactory system is so well characterized molecularly and structurally, the technique

should offer neurobiologists a rare opportunity to examine and manipulate the ways the brain processes specific

sensory information.

Katz and Rubin decided to try a technique on the olfactory bulb that had been used for

years on the visual system. Developed by Amiram Grinvald of the Weizmann Institute of Science in Rehovot, Israel,

the method, called intrinsic signal imaging, involves shining light on a patch of brain surface of a living animal.

An analysis of the light bouncing back can reveal changes in blood oxygenation (via changes in light absorption by

hemoglobin) or changes 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 in the bulbs when the anesthetized animals were

exposed to different odors. The technique worked beautifully, says Katz, with a resolution "10-fold better than in

the visual system," enabling Rubin to clearly visualize individual glomeruli. Each odor produced a unique pattern of

active glomeruli.

The optical imaging is a vast improvement over earlier methods, which entailed exposing a rat

to an odor for 45 minutes (an unnaturally long time), then killing it and looking for changes in the uptake by the

olfactory bulb of a labeled form of glucose, which also indicates neuronal activity. That approach can test only one

odorant per animal, and, Menzel adds, "one never knows whether the neuronal ... code might not change" under such

long stimulation. Katz and Rubin, he says, "used stimulation which is rather natural" in concentration and timing.



That advantage, coupled with the high resolution and the flexibility of being able to expose a single animal to

many odors at different concentrations and under various conditions, is what has researchers so excited. What's

more, the imaging can be used to guide other techniques. For example, once researchers identify the glomeruli that

respond to a particular odorant in a living animal, Katz says, it is "not that difficult" to use electrodes to

examine how the glomeruli interact, enabling researchers to check the hypothesis that active glomeruli turn up the

contrast in their signal by inhibiting the responses of their neighbors.

Olfaction is also "perfect for looking

at learning and memory," Katz says, "because one thing rodents learn very well is odors." He and others are eager to

ask how the glomerular code for an odor may change if the rat learns to associate a smell with, say, food, something

Menzel has already shown to be the case in honeybees. The possibilities don't stop there.

Katz's team now has

the technique working in mice, and because the mouse odorant receptors have been cloned, researchers can use genetic

engineering to generate receptor molecules tagged with a fluorescent protein, enabling them to associate specific

glomeruli with specific receptors, or even genetically change the receptors or their neurons to see how that affects

olfactory processing. What's more, optical imaging can likely be done on higher olfactory processing areas in the

cerebral cortex, where smells may interact with other perceptions or memories, to ask how the patterns from the

olfactory bulb are translated and transformed in those areas.

Indeed, says Grinvald, the possibilities opened

by Rubin and Katz's result are already drawing new participants into the field of olfaction. "I know of two very

good groups that jumped on this project as soon as they heard that the imaging is working so well," he says. Others

are bound to follow.


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