**4. The olfactory pathway**

*Sino-Nasal and Olfactory System Disorders*

cell types. The olfactory receptor cells in the epithelium are bipolar nerve cells. Their oval nuclei are located in the central one third of the olfactory epithelium. These cells detect smell [9]. The axons of olfactory receptor cells form the olfactory nerve, cranial nerve I. The axons traverse the cribriform plate of the ethmoid bone and project to the ipsilateral olfactory bulb where they target central neurons. Olfactory receptor cells are surrounded and cushioned by the supporting cells. The supporting cells (sustentacular cells) have their nuclei in the upper one third of the epithelium. They have cigar-shaped, elongated nuclei. Olfactory receptor cells are equipped with radiating cilia, whereas the supporting cells have microvilli at their apical surface. The basal cells have their nuclei in the lower one third of the epithelium at the base of the epithelium. They are precursor cells and actively divide after birth to replace olfactory receptor cells. The life span of olfactory receptor cells is 30–60 days. They undergo continuous replacement through the basal stem cell population [10]. Bowman's glands in the connective tissue secrete mucus to prevent constant olfactory stimulation. Bowman's glands have a duct to the surface of the olfactory epithelium. Their secretion produces a fluid environment around the olfactory cilia and may clear the cilia, facilitating the access of new odor substances. In addition, the mucus creates the ionic milieu around the cilia and contains an

odorant-binding protein to trap odorants and to bring them to cilia.

traps dust particles. Goblet cells are absent from the olfactory epithelium.

Olfactory receptor cells have a distinct dendritic process that extends to the surface of the epithelium where its tip is expanded into a club-shaped prominence, the olfactory vesicle. This bears cilia, which have the typical 9 + 2 microtubule arrangement for some of their length, but there is a long distal portion, which contains only the two central microtubule fibers. In contrast to cilia in the respiratory epithelium, the olfactory cilia (5–20) are almost immotile, and they are inserted into basal bodies in the olfactory vesicle. It is in the cilia of olfactory receptor cells where olfactory transduction takes place, that is, the conversion of an odor signal into an electrical signal. Odorant molecules bind to olfactory receptor proteins and trigger a signaling cascade that involves G-proteins and leads to the generation of action potentials (nerve impulses). These nerve impulses are sent to the brain, specifically, to the

**3. Olfactory receptor cells and transduction**

The olfactory epithelium in the nose is part of the respiratory system. The primary function of the respiratory system is respiration, that is, the system provides the gas exchange between air and blood, so blood becomes oxygenated. The part of the system involved in gas exchange is the lungs. Another part of the system is a branching system of airways that brings air to and from lungs via the respiratory movements of thoracic walls and diaphragm. This part carries out a second function of the system, which is a somewhat minor function, namely, it humidifies the air, cleans the air, and warms the air. It works more like an air-conditioning system. Along the same line, we can divide the system into two principal regions. The conducting portion includes the parts of the respiratory system that are responsible for supplying the lungs with air: nasal cavities with olfactory areas, nasopharynx, larynx and epiglottis, trachea, bronchi, bronchioles, and terminal bronchioles. The respiratory portion is the site of gas exchange and includes the respiratory bronchioles, alveolar ducts and sacs, and alveoli. The olfactory epithelium is much thicker than the respiratory epithelium, which is found in the nose and the respiratory tract, whereas the olfactory epithelium is found only on the roof of nasal cavity. The respiratory epithelium contains goblet cells that secret a mucus which covers the epithelium and

**4**

olfactory bulb.

The olfactory pathway starts with olfactory receptor neurons in the olfactory epithelium that send their axons to the ipsilateral olfactory bulb. There, they make synaptic contacts with central neurons in spherical structures, the olfactory glomeruli (2000 per bulb in the mouse). In the olfactory bulb, sensory information is processed in olfactory glomeruli. Each glomerulus is a discrete anatomical and functional unit and serves as an anatomical address dedicated to collecting and processing of specific molecular features about the olfactory environment conveyed to it by olfactory receptor cell axons expressing specific olfactory receptor proteins [23–25]. Thus, the glomeruli in the olfactory bulbs are organized chemotopically [26, 27], analogous to visuotopy, in visual systems, and tonotopy, in auditory systems. Olfactory information is extensively processed at the level of the glomeruli through feedforward and feedback inhibition and modulation provided by centrifugal neurons. Information is subsequently conveyed to higher-order olfactory center such as the olfactory cortex in vertebrates.

Olfactory receptor cells in the olfactory epithelium that have the same type of olfactory receptor, that is, they express the same olfactory receptor gene (1 of ~1000), send their axons to the same glomerulus (1 of 2000) in the olfactory bulb. This is an example of sensory axons converging on one glomerulus in the brain. In the olfactory bulb, olfactory receptor cell axons synapse on mitral/tufted cells. Glomerular mitral/tufted cells process odor signals coming from the nasal olfactory epithelium. The central neurons in the olfactory bulb, such as the mitral and tufted cells, project to higher olfactory centers. Twenty to 50 neurons output neurons (mitral/tufted cells), innervate each glomerulus, and project out of the olfactory bulb. Mitral cells that innervate different glomeruli typically respond to different types of odorants. A given odorant can activate mitral cells in several or many glomeruli. Odorant identity

can be encoded through a combination of olfactory receptors, where each olfactory receptor detects one molecular feature of the odorant. Mitral and tufted cells send their axons through the lateral olfactory tract to the olfactory cortex, which includes the anterior olfactory nucleus, the piriform cortex, parts of the amygdala, the olfactory tubercle, and parts of the entorhinal cortex. From the amygdala, olfactory information is passed on to the hypothalamus and from the entorhinal cortex to the hippocampus. Olfactory information can be sent to the orbitofrontal cortex through the thalamus from olfactory cortical areas, except the anterior olfactory nucleus. Centrifugal fibers that originate outside of the olfactory bulb project to the olfactory bulb from the basal forebrain (horizontal limb of the diagonal band) and midbrain (locus coeruleus and raphe). The functional significance is a possible modulation of olfactory processing during different behavioral states.

Olfactory disorders and dysfunctions have received attention because they can result in serious problems, such as our inability to smell warning odors (fire, gas) and an impaired ability to taste food through retronasal stimulation of olfactory receptors [3]. Anosmia (loss of smell) and hyposmia (diminished smell) result from a number of etiologies. Specific anosmia refers to lowered sensitivity to a specific odorant and general anosmia denotes complete lack of olfactory sensation. Dysosmia (distorted smell) and phantosmia (phantom smells) may accompany these conditions. Cacosmia refers to olfactory hallucinations of repugnant smells.
