NEUROBIOLOGY: Mapping Smells in the Brain

[bjf]

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

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.

[DrSmellThis]

Great post, and good news for

those debating how smell works. Turin and others will be following this closely, as the brain info is an important

piece of the puzzle.