The Smell Files

By Sarah Richardson|Tuesday, August 01, 1995
RELATED TAGS: SENSES
Scent, the most primal of all senses, is arguably the most complex. The human nose contains millions of odor receptors of a thousand kinds--far more variety than is required for color vision or taste. How does the brain make sense of this flurry of signals? An essential first step, two groups of neurobiologists have recently found, is an orderly filing system. As they enter the brain from the different receptors, the hundreds of signals, each one representing a distinct odor component, are sorted into little round files called glomeruli--one type of signal per file.

Odor receptors lie in the mucous membranes high in the nose, on hairlike cilia that are the tips of dendrites--the receiving ends of the olfactory neurons. An individual neuron carries many copies of just one kind of receptor. When a smell molecule binds to a receptor, the receptor sends a signal up the dendrite to the cell body. From there it travels down the neuron’s sending arm, the axon. The axon passes through a hole in the bone into one of the olfactory bulbs--twin structures, each roughly the size of a small grape, that are lodged above each nostril on the underside of the brain.

The glomeruli (the word is Latin for little balls) line the olfactory bulbs. Each one is a neural junction, a place where the axons from roughly 2,000 olfactory neurons meet and pass signals to the dendrites of some 30 mitral cells. The mitral cells then refine the signals and relay them to the olfactory cortex, a higher region in the brain.

That much has been known for some time now. And so it has also been clear for some time that glomeruli must play a crucial role in organizing scent perception. But what hasn’t been clear, because the neural connections hadn’t been mapped out, is exactly what that role is. Past studies had shown that different odors activate different subsets of glomeruli; and yet a single glomerulus was also thought to respond to a variety of odors. Is it receiving information from neurons bearing different receptors, or does it receive information from only one kind of olfactory receptor?

By using molecular probes that tag particular olfactory receptors, researchers have recently untangled some of the neural wiring in the olfactory bulbs of rats and shown which wire connects to which junction. Both groups--one led by Richard Axel at the Howard Hughes Medical Institute at the Columbia College of Physicians and Surgeons and the other by Linda Buck of Harvard Medical School--found that glomeruli don’t get mixed signals. Instead, each gets a very clear one: only neurons bearing one kind of receptor converge on a glomerulus. In fact, it looks as though there are roughly as many glomeruli as there are kinds of olfactory receptors. A glomerulus for a particular receptor seems to be located in the same place in each of the two olfactory bulbs, and in the same place in all rats.

Each receptor and each glomerulus, Axel explains, responds to just one part of a smell molecule’s structure rather than the whole molecule. What you’re doing is essentially dissecting the odorous image, he says. You deconstruct the image such that the individual components of a given odor--even an odor elicited by a single molecule--will react with different receptors simultaneously. Because different molecules may share some structural features, a single glomerulus may be activated by different odors, even though it receives information from only one kind of receptor.

Any given odor, however, is distinguished by the pattern of glomeruli it activates. Based on this molecular fingerprint, the brain can somehow recognize nearly 10,000 scents, despite having a repertoire of only a thousand olfactory receptors. Glomeruli help us do that not only by sorting the signals but also by enhancing sensitivity, says Buck. The convergence of similar neurons in a single glomerulus helps the brain get enough of a sample to recognize the odor, even if it is present in very small quantities.

This method of identifying odor components may also explain why we can recognize odors we haven’t smelled in decades. Without stimulation, says Buck, olfactory neurons will die. Since an individual neuron responds to a component that many odors share rather than to one particular odor, it is stimulated often. That may keep our neurons in fighting trim, Buck speculates, and able to recognize a distinctive pattern of a scent long after it was first encountered.

The most tantalizing question of all, however, remains unanswered. How is the map of activated glomeruli decoded in the brain? The precise positioning of glomeruli within the olfactory bulb probably simplifies the brain’s job somewhat. If the position to which an olfactory neuron projects is fixed, says Axel, then the brain can use anatomic position as an indicator of odor quality. But to find out if that’s what is really going on, he and Buck will have to untangle the nerve knots some more. The next question is to go one step further into the cortex, says Axel, and ask how the mitral cells project to the cortex. That might give us some indication of how this map is read.
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