How the Nose Knows

Neurobiologists have sniffed out how the nose uses relatively few kinds of molecular sensors to discriminate among thousands of odors. As reported in today's Cell, different smells activate unique suites of these sensors. The sensors, called odorant receptors, are so sensitive to the chemical makeup of incoming odors that just a slight difference turns a smell from sweet to rancid.

For almost a decade, neurobiologists have suspected that odors activate different sets of receptors in the mammalian nose. A team led by Linda Buck of Harvard Medical School in Boston was able to test this proposition with mouse olfactory nerve cells. For each of a dozen odors, Takaaki Sato from the Life Electronics Research Center in Amagasaki, Japan, looked to see which cells increased their calcium concentration, which occurs as nerve cells fire. In addition, Bettina Malnic of Harvard determined which receptor genes were active in individual nerve cells to learn which odor receptors were present in each. "This was a very elegant and clever approach," says neurobiologist Stuart Firestein of Columbia University in New York City.

Each nerve cell contained one distinct type of receptor that was sensitive to more than one odor. Although only a small percentage of neurons were active at one time, every odor stimulated a unique subset of receptors. Changing the concentration also alters slightly which nerve cells fire a signal to the brain. Although the team studied only 13 of the 1000 different receptors and tested them with relatively few chemicals, the results "give us the beginning of an interesting set of rules" for odor discrimination, says Firestein. Thus, one chemical can smell delightful while an almost identical one can be repugnant because they activate a slightly different suite of receptors.

The techniques used in these experiments can help researchers identify the kinds of receptors that recognize specific odors, says Buck. Other researchers think this work could eventually lead to synthetic odors that could be used in pest control. More broadly, a better grasp of how olfactory receptor sensitivity depends on chemical structure could reveal universal secrets of receptor function, Firestein adds.