Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
The olfactory system of mammals can distinguish a large number of volatile chemicals of varied size and shape. Remarkably, the discriminatory power of this system is such that even a slight change in an odorant's structure can dramatically alter its perceived odor. Moreover, pheromones, though also detected by the olfactory system, can elicit specific behavioral and hormonal responses that general odorants do not. To explore the molecular bases of odorant and pheromone detection and discrimination, we have taken a molecular approach, asking first how these chemicals are detected, and then using genes encoding the detectors to explore how sensory information is organized, or encoded, in the nervous system. In initial studies, we identified a multigene family encoding ~1000 different odorant receptors (ORs) that are expressed by sensory neurons in the nasal olfactory epithelium (OE). Each OE neuron expresses one OR gene. We found that neurons with the same OR are scattered in the OE, but that their axons converge in a few invariant glomeruli in the olfactory bulb, giving rise to a stereotyped map of OR inputs in which the segregation of inputs from different ORs is perpetuated. In the vomeronasal organ (VNO), which is thought to detect pheromones, we and others found two smaller families of olfactory receptors. The expression patterns of these receptors resembles those of ORs in the OE, suggesting that a similar mode of information processing may be involved in the initial detection of odorants and pheromones. Recently, we used a combination of calcium imaging of single OE neurons and single cell RT-PCR to identify ORs that recognize odorants with related structures, but varied odors. Our studies show that the olfactory system uses a combinatorial receptor coding scheme to encode odor identities: different odorants are encoded by different combinations of ORs, but each OR serves as one component of the "receptor codes" for many odorants. Our studies further suggest that changes in perception that accompany changes in an odorant's structure may be a direct consequence of a change in receptor code.