The question of olfactory information encoding has been a concern for a long time. One main problem was to find a theory or model that would predict the odorous properties of a given molecule. Although the fragrance industry spends a lot of money on the creation of new - and hopefully smelly - molecules, no model exists which could predict the smell of any given molecule. The search for new odorants is still a very expensive procedure based on trial and error. Therefore, a universal model of stereochemical -odor interaction would greatly assist the search for new odorants.
Several models have been proposed to explain how the olfactory system discriminates between odorants. In the early sixties Mozell hypothesized that the chromatography of a molecule would determine its processing [31, 32]. According to Mozell, the olfactory receptors, which are located on the cilia of the olfactory neurons, are covered by a mucous layer and odorants have to cross this mucus before reaching the receptor cell. His theory was based on experiments using frog olfactory epithelium. Although no clear evidence has been presented that absorption of odorants is irrelevant to its interaction with the receptors, this theory has received less attention during recent years. Nevertheless, recent work on humans suggests that absorption could have implications for olfactory perception . Another model indicates that olfactory recognition is mainly based on a few basic odors and that combination of these odors encodes the olfactory information [34, 35]. This model claims that olfaction works according to physiological principles similar to those governing vision. This assumption was mainly based on experiments on specific anosmias to isovaleric acid. Further experiments with other odorants were not able to confirm this model. Another theory receiving interest from the media is an old idea  reactivated by Turin . According to this theory, olfactory coding could be based on vibration properties of the odorants. Recent work, however, indicates that this model can not predict the olfactory characteristics of a given molecule .
Since odorants are chemical structures, the existence of a ligand-receptor interaction has been claimed for many years, and was finally substantiated in 1991 by the discovery of a large family of seven transmembrane receptor proteins, expressed exclusively in the olfactory neuro-epithelium. These olfactory receptors (ORs) are encoded by approximately 1000 genes in the mouse, or approximately 1% of its genome . While the mouse expresses approximately 850 of these genes, the rest being pseudogenes, humans have far fewer functional ORs (approximately 350) . Although this seems to indicate a loss in function, the simple equation ''less receptors = less function'' is currently under debate and some studies argue that humans have a very high preservation rate for specially important ORs [41-43].
The discovery of the OR superfamily led to a renaissance of olfactory research. During the last decade, potential OR binding sites  and the topographical organization and distribution of the ORs within the olfac tory epithelium have been partly identified [45-47]. A recent finding has been the astonishingly high degree of organization found within the peripheral olfactory system. The first striking observation was that, among all the potentially expressible OR, every ORN expresses only one single OR gene [48, 49]. Furthermore, axons from all ORN expressing the same OR, whatever their location within the olfactory epithelium, project into two glomeruli in each olfactory bulb. This organization is called glomerular convergence . Thus, a large glomerular map in the bulb, containing hundreds of glomeruli, will correspond to all OR expressed in the olfactory neuro-epithelium. Molecular and electrophysiological studies revealed that OR are not selective for only one odorant, but numerous molecules bind with varying affinities to a certain OR. A given receptor may bind to a molecule with a given carbon chain length, but may lose binding affinity as the agonist's chain length increases. Similarly, the OR binding affinity for a molecule may dramatically change upon modification of the functional groups (aldehydes, ketones, acids, esters, alcohols, etc) of this molecule [51, 52]. In addition, every odorant is recognized not by one but by several ORs simultaneously, depending on its particular chemical properties. At the level of the glomerular map this leads to a specific activation pattern for each odorant . This odor-specific activation pattern is believed to be responsible for the recognition of and distinction between different odorants .
However, as previously mentioned and although the olfactory receptor theory adequately explains how olfactory coding could work, olfactory research is still a long way away from predicting the odor of a molecule based solely on the stereo-chemical properties of the latter.
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