The olfactory system has received considerable attention in recent years because of the intriguing biologic question of how a simple sense organ such as the olfactory epithelium and its brain representation, which apparently lacks a high degree of complexity, can mediate discrimination of more than 10,000 different odors. One part of the answer to this question is that there are many different odorant receptors.
There are approximately 500 functional olfactory genes in humans, accounting for about 2% of the human genome. The amino acid sequences of odorant receptors are very diverse, but all the odorant receptors are G-protein-coupled receptors (GPCRs). When an odorant molecule binds to its receptor, the G-protein subunits (α, β, γ) dissociate (Figure 1). The α-subunit activates adenylyl cyclase to catalyze the production of cAMP, which acts as a second messenger to open cation channels, increasing the permeability to Na+, K–, and Ca2+. The net effect is an inward-directed Ca2+ current which produces the graded receptor potential. This then opens Ca2+-activated Cl– channels, further depolarizing the cell due to the high intracellular Cl– levels in olfactory sensory neurons. If the stimulus is sufficient for the receptor potential to exceed its threshold, an action potential in the olfactory nerve (first cranial nerve) is triggered.
Fig1. Signal transduction in an odorant receptor. A) Olfactory receptors are examples of G-protein-coupled receptors; ie, they are associated with three G-protein subunits (α, β, γ). B) When an odorant binds to the receptors, the subunits dissociate. The α-subunit of G-proteins activates adenylyl cyclase to catalyze production of cAMP. cAMP acts as a second messenger to open cation channels. Inward diffusion of Na+ and Ca2+ produces depolarization.
A second part of the answer to the question of how 10,000 different odors can be detected lies in the neural organization of the olfactory pathway. Although there are millions of olfactory sensory neurons, each expresses only one of the 500 olfactory genes. Each neuron projects to one or two glomeruli (Figure 2). This provides a distinct two-dimensional map in the olfactory bulb that is unique to the odorant. The mitral cells with their glomeruli project to different parts of the olfactory cortex.
Fig2. Basic neural circuits in the olfactory bulb. Note that olfactory receptor cells with one type of odorant receptor project to one olfactory glomerulus (OG) and olfactory receptor cells with another type of receptor project to a different OG. Solid black arrows signify inhibition via GABA release, and white arrows signify excitatory connections via glutamate release. CP, cribriform plate; Gr, granule cell; M, mitral cell; PG, periglomerular cell; T, tufted cell. (Adapted with permission from Mori K, et al: The olfactory bulb: coding and processing of odor molecular information, Science 1999 Oct 22; 286(5440):711–715.)
The olfactory glomeruli demonstrate lateral inhibition mediated by periglomerular cells and granule cells. This sharpens and focuses olfactory signals. In addition, the extracellular field potential in each glomerulus oscillates, and the granule cells appear to regulate the frequency of the oscillation. The exact function of the oscillation is unknown, but it probably also helps focus the olfactory signals reaching the cortex.
