How The Nose Knows: Research On Smell Boosted

The sense of smell, notes LSU biology professor John Caprio, originally evolved to detect water-soluble chemicals like amino acids. The ability to detect volatiles in air is an adaptation of the original mechanism.

"Amino acids are the signature of life," he said. "Every living thing sheds amino acids. The olfactory system evolved to pick up information. Odors help an animal find food, avoid predators and locate a mate."

We know a lot about smell, Caprio said, but there is a lot we don't know. "For instance, we don't know how the brain can distinguish between the smell of garbage, the smell of a rose or the smell of burning electrical wiring."

Working to fill this gap in our knowledge, Caprio and two other researchers recently received a $1.6 million, 5-year grant from the National Institutes of Health to study just what goes on between the nose and the brain.

And Caprio, who invented the famed fish-lure, "Gottabite," is a good one to sniff out the answers.

To uncover these secrets of nature, he has developed a sophisticated method for probing the brains of catfish. The fish is anesthetized and clamped in a special holding block while a stream of water is passed over its gills and nose. Electrodes are inserted into the fish's nose and brain, and different chemicals are injected, one at a time, into the nose.

Intermingled in the catfish's nose are different types of olfactory receptor nerves. These extend to the olfactory bulb in the forebrain where each type ends in its own region. This makes it relatively easy for Caprio's electrodes to detect what type of receptor nerve is being stimulated by the chemical in the water.

Complicating this not-too-simple sensory system is the fact that each receptor nerve can detect more than a single odor. This is because proteins produced by the receptor nerves bind to some chemicals but not to others. When one of the proteins binds to an odor molecule, the nerve is stimulated and fires a signal to the brain. The way the brain interprets the responses from hundreds of thousands of receptor nerves is what produces the different odors we detect, Caprio said.

The catfish's olfactory system is similar to a human's, but simpler. For example, a catfish produces about 100 different proteins in its receptor nerves; a human about 1,000.

Working with Thomas Finger at the University of Colorado Medical Center and Peter Sorensen of the University of Minnesota's Department of Wildlife and Fisheries, Caprio and his colleagues are investigating the different areas of the olfactory bulb to determine what different odors stimulate different neurons. They are also trying to determine which odor-producing molecules bind to the different types of olfactory proteins on the nerve endings.

This is all basic information, Caprio said. "If you don't know how something works, you can't fix it when it breaks."

And sometimes it breaks. "People who lose their sense of smell due to an injury like whiplash, or to chemotherapy, don't want to eat," Caprio said. That is because the sense of smell and the sense of taste are so closely bound up.

"If you blindfold someone and give him a jellybean, he'll be able to tell you whether it's licorice or cherry. But if he holds his nose while he's eating the jellybean, all he'll be able to tell you is that it's sweet. That's because the tongue can taste primarily sweet, sour, salty and bitter. It's the volatiles in the jellybean stimulating the olfactory nerves that tell you what flavor it really is."

In an interesting side note, Caprio observed that a pheromone which excites sex in an elephant is the same one that excites sex in a moth. But, contrary to the claims of certain perfume manufacturers, no human sex pheromones have yet been identified, he said.

Another question Caprio would like answered, though it is not specifically addressed in this research, is why vertebrates developed two different systems to detect chemicals. Although taste and smell may seem similar, the two systems are quite different, he said. Odorants touch the olfactory nerves directly, but the nerves involved in taste are stimulated indirectly, through taste cells enclosed within taste buds. Also, the two senses are embedded in two different areas of the brain. Olfactory nerves terminate in the forebrain, and the nerves for taste terminate in the hindbrain.

Another mystery is why odors can evoke intense memories, but taste, at least in the catfish, seems not to link at all with memory.

These are some of the things Caprio hopes to find out.