Sense of smell and mechanism of olfaction

It is claimed that humans can perceive many thousands of different odorous molecules, termed odorants, and that they can discriminate at least two to three thousand of these. It is also well known that even slight alterations in the structure of an odorant can lead to profound changes in perceived odor quality. One commonly cited example is carvone, whose l- and d-stereoisomers are perceived as spearmint and caraway, respectively. However, more subtle molecular alterations can also generate striking changes in perception.

The fine discriminatory power of the mammalian olfactory system is likely to derive from information-processing events that occur at several distinct anatomical sites: the olfactory epithelium of the nasal cavity, where odors are first sensed by olfactory sensory neurons; the olfactory bulb, where information received from the sensory neurons is presumably processed; and the cortex, where information received from the olfactory bulb is thought to be further refined to allow for the discrimination of thousands of different odors. 

The olfactory epithelium contains three predominant cell types: the olfactory sensory neuron; the supporting, or sustentacular, cell; and the basal, or stem, cell. Olfactory neurons are the only mammalian neurons that are known to turn over throughout life. They are continuously replaced from the basal layer of stem cells. Two morphologically distinguishable types of dividing basal cell have been identified in mammals, the horizontal basal cell and the globose basal cell. At present, it is not clear what lineage relationship these two cell types bear to each other, but both have been proposed as stem cell precursors to the olfactory neuron.

The olfactory neuron is a bipolar cell that extends a single dendrite to the epithelial surface. From the dendritic terminus, numerous fine cilia extend into the layer of mucus that lines the nasal lumen. The cilia are the loci of the molecular transduction machinery, as has been shown by physiological and biochemical experiments.

Each olfactory neuron projects an unbranched axon to the olfactory bulb, where it forms synapses within specialized regions of neuropil, called glomeruli, with periglomerular interneurons and the two major output neurons of the bulb, the mitral and tufted cells. The bulbar neurons, in turn, project to the olfactory cortex. It is thought that the patterns of synapses formed in the olfactory bulb by olfactory neurons that recognize different odorants might constitute elementary odor codes. The remarkable size and diversity of the odorant receptor multigene family in mammals suggests that odor discrimination relies heavily on the initial event in olfactory perception, the interaction of odorant receptor with odorant. In this respect, olfaction contrasts sharply with color vision, where signals derived from only three peripheral receptor types, the three color opsins, are processed to allow the perception of a multitude of different hues. The extremely large number of odorant receptor genes further suggests that individual receptors could be fairly specific, each one recognizing only one or a small set of structurally similar odorants.

The olfactory system is thought to respond to extremely low concentrations of odorants and to have a fast recovery of perceptual sensitivity. In recent years, significant advances have been made in the understanding of the signal-transduction events that take place when an olfactory sensory neuron is exposed to an odorant. Before discussing the biochemical events involved in the signal-transduction process, it is instructive to consider the sensitivity of the olfactory system at the level of perception versus the individual neuron. https://www.ncbi.nlm.nih.gov/books/NBK28226/