Anatomy of the Olfactory System
The olfactory epithelium resides in an area of a few square centimeters in the superior nasal cavity on the cribriform plate, upper septum, and medial superior and middle turbinates in the olfactory cleft. The pseudostratified columnar epithelium is thicker than the surrounding respiratory epithelium and can be visualized in the upper nasal cavity as paler in appearance than the pinker surrounding respiratory epithelium. In human fetuses, the olfactory mucosa is a continuous zone of olfactory epithelium, but in adults, clumps of respiratory epithelium are mixed with the o lfactory epithelium. This intermixed respiratory mucosa increases with age, presumably due to a loss of primary olfactory neurons.
The olfactory epithelium consists of the olfactory mucosa and the underlying lamina propria, which are separated by a basal lamella. The cell types of the mucosa consist of the olfactory receptor neurons, the sustentacular and microvillar cells, and the basal cells ( Figs. 4.1 and 4.2 ). The olfactory receptor neurons (ORN) are bipolar neurons with dendrites extending to the epithelial surface and axons extending intracranially and synapsing at the olfactory bulb. The dendrite has a thickened ending or knob containing nonmotile cilia which increase the functional surface area of the olfactory epithelium to 22 cm2 and hold the olfactory receptors that bind odorants. The unmyelinated axon of each ORN joins other axons to form myelinated fascicles or fibers (filae olfactoria). The ~50 filae of cranial nerve (CN) I travel through the foramina of the cribriform plate to synapse in the olfactory bulb. The sustentacular cells insulate the bipolar receptor neurons and regulate the composition of the mucus covering the epithelium. They also feature high concentrations of cytochrome P450, responsible for metabolizing foreign molecules and protecting the olfactory epithelium. The function of the microvillar cells is currently unknown. Located within the lamina propria are Bowman′s glands, which send ducts through the basal lamella to the surface of the epithelium. These glands provide the mucus layer, which covers the cilia of the ORN dendrites. Hydrophilic odorant substances dissolve in the aqueous mucus, whereas hydrophobic molecules interact with olfactory binding proteins before binding with olfactory receptors.
Olfactory epithelium is unique in its ability to replace damaged or injured neural tissue. Two types of basal cells, globose and horizontal cells, are responsible for regeneration of the olfactory epithelium. After injury, basal cells can divide and differentiate into all cell lineages, including olfactory neurons. The ability of the olfactory epithelium to regenerate appears to decrease with age or with increasing severity of injury, resulting in increased replacement with respiratory epithelium.
In 2004, the Nobel Prize for Physiology or Medicine was awarded to Richard Axel and Linda B. Buck for the discoveries of the family of genes coding for the olfactory receptors and the description of the organization of the olfactory system.9 The identification and characterization of mammalian odorant receptors has been reviewed by Reed.10 The olfactory receptors on the cilia of the ORNs are transmembrane G-protein coupled receptors. After the binding of an odorant to the receptor, cAMP is generated, resulting in depolarization of the cell and firing of an action potential along the axon. Each ORN contains only one type of olfactory receptor. The human genome contains 1,000 olfactory receptor genes, of which 350 functionally code for unique receptors. Most odorants can bind to and stimulate multiple olfactory receptors, whereas each receptor can likely bind multiple odorants; this combination allows for the identification of thousands of different odors by humans. The axons of ORNs expressing the same olfactory receptors converge and synapse on the same glomerulus within the olfactory bulb.
The olfactory bulb lies in the anterior cranial fossa inferior to the frontal lobe ( Fig. 4.3 ). Olfactory nerve bundles synapse with the second-order neurons within thousands of glomeruli of the bulb. Within the bulb are located principal cells (mitral and tufted cells) and intrinsic neurons or interneurons. Axons from mitral and tufted cells leave the bulb as the lateral olfactory tract. These extend to the olfactory cortex, which includes the anterior olfactory cortex connecting the two olfactory bulbs, olfactory tubercle, the pyriform cortex (the main olfactory discrimination area), the cortical nucleus of the amygdala, and the entorhinal area, which projects to the hippocampus. Further connections include the medial dorsal nucleus of the thalamus, which is involved in conscious perception of odors, whereas the limbic system connections may be involved in the formation of strong olfactory memories.
Odorants reach the olfactory cleft and olfactory epithelium either anteriorly through the nares or retro-nasally through the oropharynx and nasopharynx into the nasal cavity. This retronasal airflow is responsible for the appreciation of the flavor of food and is why patients with olfactory disorders may present initially with complaints about taste, even with intact taste discrimination.11 Ophthalmic and maxillary branches of the trigeminal nerve are present within the nasal cavity and respond to chemical irritants, including ammonia, and are responsible for resulting nasal mucosal edema, mucous secretion, tearing, and sneezing.