Posteriorly, the olfactory tract divides into medial and lateral olfactory striae. The medial stria contains fibers from the anterior olfactory nucleus; these pass to the opposite side via the anterior commissure. Fibers in the lateral stria originate in the olfactory bulb, give off collaterals to the anterior perforated substance, and terminate in the nuclei of the amygdaloid complex and the prepiriform area (also referred to as the lateral olfactory gyrus). The latter represents the primary olfactory cortex, which in humans occupies a restricted area on the anterior aspect of the parahippocampal gyrus and uncus (area 34 of Brodmann; see Figs. 21-1 and 21-2). Thus olfactory impulses reach the cerebral cortex without a relay through the thalamus; in this respect also, olfaction is unique among sensory systems. From the prepiriform cortex, fibers project to the neighboring entorhinal cortex (area 28 of Brodmann) and the medial dorsal nucleus of the thalamus; the amygdaloid nuclei connect with the hypothalamus and septal nuclei. The role of these latter structures in olfaction is not well understood, but presumably they subserve reflexes related to eating and sexual function. As with all sensory systems, feedback regulation occurs at every point in the afferent olfactory pathway.
In quiet breathing, little of the air entering the nostril reaches the olfactory mucosa; sniffing carries the air into the olfactory crypt, which contains the olfactory receptors. To be perceived as an odor, an inhaled substance must be volatile—that is, spread in the air as very small particles—and soluble in water. Molecules provoking the same odor seem to be related by their shape more than by their chemical quality. When a jet of scented vapor is directed to the sensory epithelium, as by sniffing, a slow negative potential shift called the electroolfactogram (EOG) can be recorded from an electrode placed on the mucosa. The conductance changes that underlie this receptor potential are induced by molecules of odorous material dissolved in the mucus overlying the receptor.
The transduction of odorant stimuli to electrical signals is mediated in part by a guanosine triphosphate (GTP)-dependent adenylyl cyclase (“G protein”). Like other cyclic adenosine monophosphate (AMP) pathways, this one utilizes the same intracellular second messenger, which opens a voltage-gated calcium channel in the receptor. There follow conformational changes in transmembrane receptor proteins and a series of intracellular biochemical events that generate axon potentials.
Intensity of olfactory sensation is determined by the frequency of firing of afferent neurons. The quality of the odor is thought to be provided by “cross-fiber” activation and integration, as described earlier, because the individual receptor cells are responsive to a wide variety of odorants and exhibit different types of responses to stimulants—excitatory, inhibitory, and on–off responses have been obtained. The olfactory potential can be eliminated by destroying the olfactory receptor surface or the olfactory filaments. The loss of EOG occurs 8 to 16 days after severance of the nerve; the receptor cells disappear, but the sustentacular (Sertoli) cells are not altered. As a result of division of the basal cells of the olfactory epithelium, the olfactory receptor cells are constantly dying and being replaced by new ones. In this respect, the chemoreceptors, both for smell and for taste, constitute one of the few examples of neuronal regeneration in humans.
The trigeminal system also participates in chemesthesis through undifferentiated receptors in the nasal mucosa. These receptors have little discriminatory ability but a great sensitivity to irritant stimuli. The trigeminal afferents also release neuropeptides that result in hypersecretion of mucus, local edema, and sneezing. Finally, stimulation of the olfactory pathway at cortical sites of the temporal lobe may also induce olfactory experiences.