Sense of Smell Wins Nobel Prize (cont.)

Each odorant receptor first activates a G protein, to which it is coupled. The G protein in turn stimulates the formation of cAMP (cyclic AMP). This messenger molecule activates ion channels, which are opened and the cell is activated. Axel and Buck showed that the large family of odorant receptors belongs to the G protein-coupled receptors (GPCR).

All the odorant receptors are related proteins but differ in certain details, explaining why they are triggered by different odorous molecules. Each receptor consists of a chain of amino acids that is anchored into the cell membrane and traverses it seven times. The chain creates a binding pocket where the odorant can attach. When that happens, the shape of the receptor protein is altered, leading to G protein activation.

Each Olfactory Cell is Unique

Independently, Axel and Buck showed that every single olfactory receptor cell expresses one and only one of the odorant receptor genes. Thus, there are as many types of olfactory receptor cells as there are odorant receptors. It was possible to show, by registering the electrical signals coming from single olfactory receptor cells, that each cell does not react only to one odorous substance, but to several related molecules -- albeit with varying intensity.

Buck's research group examined the sensitivity of individual olfactory receptor cells to specific odorants. By means of a pipette, they emptied the contents of each cell and showed exactly which odorant receptor gene was expressed in that cell. In this way, they could correlate the response to a specific odorant with the particular type of receptor carried by that cell.

Most odors are composed of multiple odorant molecules, and each odorant molecule activates several odorant receptors. This leads to a combinatorial code forming an "odorant pattern" - somewhat like the colors in a patchwork quilt or in a mosaic. This is the basis for our ability to recognize and form memories of approximately 10,000 different odors.

Activating the Brain

The finding that each olfactory receptor cell only expresses one single odorant receptor gene was highly unexpected. Axel and Buck continued by determining the organization of the first relay station in the brain. The olfactory receptor cell sends its nerve processes to the olfactory bulb, where there are some 2,000 well-defined microregions, glomeruli. There are thus about twice as many glomeruli as the types of olfactory receptor cells.

Axel and Buck independently showed that receptor cells carrying the same type of receptor converge their processes into the same glomerulus, and Axel's research group used sophisticated genetic technology to demonstrate the role of the receptor in this process. The convergence of information from cells with the same receptor into the same glomerulus demonstrated that also glomeruli exhibit remarkable specificity.

Conscious of a Smell

In the glomeruli there are not only the nerve processes from the olfactory receptor cells but also their contacts with the next level of nerve cells, the mitral cells. Each mitral cell is activated only by one glomerulus, and the specificity in the information flow is thereby maintained. Via long nerve processes, the mitral cells send the information to several parts of the brain. Buck showed that these nerve signals in turn reach defined micro regions in the brain cortex. Here the information from several types of odorant receptors is combined into a pattern characteristic for each odor. This is interpreted and leads to the conscious experience of a recognizable odor.

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Last Editorial Review: 10/4/2004