All environmental chemicals necessary for life enter the body by the nose and mouth. The senses of smell (olfaction) and taste (gustation) monitor those chemicals, determine the flavor and palatability of foods and beverages, and warn of dangerous environmental conditions, including fire, air pollution, leaking natural gas, and bacteria-laden foodstuffs. These senses contribute significantly to quality of life and, when dysfunctional, can have untoward physical and psychological consequences. A basic understanding of these senses in health and disease is critical for the physician, since thousands of patients present to doctors' offices each year with complaints of chemosensory dysfunction. Among the more important developments in neurology has been the discovery that decreased smell function is perhaps the first sign of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), signifying their “presymptomatic” phase.
Odorous chemicals enter the nose during inhalation and active sniffing as well as during deglutition. After reaching the highest recesses of the nasal cavity, they dissolve in the olfactory mucus and diffuse or are actively transported to receptors on the cilia of olfactory receptor cells. The cilia, dendrites, cell bodies, and proximal axonal segments of these bipolar cells are situated within a specialized neuroepithelium that covers the cribriform plate, the superior nasal septum, the superior turbinate, and sectors of the middle turbinate (Fig. 29-1). Each of the ˜6 million bipolar receptor cells expresses only one of ˜450 receptor protein types, most of which respond to more than a single chemical. When damaged, the receptor cells can be replaced by stem cells near the basement membrane. Unfortunately, such replacement is often incomplete.
Anatomy of the olfactory neural pathways, showing the distribution of olfactory receptors in the roof of the nasal cavity. [Copyright David Klemm, Faculty and Curriculum Support (FACS), Georgetown University Medical Center; used with permission.]
After coalescing into bundles surrounded by glia-like ensheathing cells (termed fila), the receptor cell axons pass through the cribriform plate to the olfactory bulbs, where they synapse with dendrites of other cell types within the glomeruli (Fig. 29-2). These spherical structures, which make up a distinct layer of the olfactory bulb, are a site of convergence of information, since many more fibers enter than leave them. Receptor cells that express the same type of receptor project to the same glomeruli, effectively making each glomerulus a functional unit. The major projection neurons of the olfactory system—the mitral and tufted cells—send primary dendrites into the glomeruli, connecting not only with the incoming receptor cell axons but with dendrites of periglomerular cells. The activity of the mitral/tufted cells is modulated by the periglomerular cells, secondary dendrites from other mitral/tufted cells, and granule cells, the most numerous cells of the bulb. The latter cells, which are largely GABAergic, receive inputs from central brain structures and modulate the output of the mitral/tufted cells. Interestingly, like the olfactory receptor cells, some cells within the bulb undergo replacement. Thus, neuroblasts formed within the anterior subventricular zone of the brain migrate along the rostral migratory stream, ultimately becoming granule and periglomerular cells.
Schematic of the layers and wiring of the olfactory bulb. Each receptor type (red, green, blue) projects to a common glomerulus. The neural activity within each glomerulus is modulated by periglomerular cells. The activity of the primary projection cells, the mitral and tufted cells, is modulated by granule cells, periglomerular cells, and secondary dendrites from other mitral and tufted cells. (From www.med.yale.edu/neurosurg/treloar/index.html.)
The axons of the mitral and tufted cells synapse within the primary olfactory cortex (POC) (Fig. 29-3). The POC is defined as the cortical structures that receive direct projections from the olfactory bulb, most notably the piriform and entorhinal cortices. Although olfaction is unique in that its initial afferent projections bypass the thalamus, persons with damage to the thalamus can exhibit olfactory deficits, particularly ones of odor identification. Those deficits probably reflect the involvement of thalamic connections between the primary olfactory cortex and the orbitofrontal cortex (OFC), where odor identification occurs. The close anatomic ties between the olfactory system and the amygdala, hippocampus, and hypothalamus help explain the intimate associations between odor perception and cognitive functions such as memory, motivation, arousal, autonomic activity, digestion, and sex.
Anatomy of the base of the brain showing the primary olfactory cortex.
Tastants are sensed by specialized receptor cells present within taste buds: small grapefruit-like segmented structures on the lateral margins and dorsum of the tongue, the roof of the mouth, the pharynx, the larynx, and the superior esophagus (Fig. 29-4). Lingual taste buds are embedded in well-defined protuberances termed fungiform, foliate, and circumvallate papillae. After dissolving in a liquid, tastants enter the opening of the taste bud—the taste pore—and bind to receptors on microvilli, small extensions of receptor cells within each taste bud. Such binding changes the electrical potential across the taste cell, resulting in neurotransmitter release onto the first-order taste neurons. Although humans have ˜7500 taste buds, not all harbor taste-sensitive cells; some contain only one class of receptor (e.g., cells responsive only to sugars), whereas others contain cells sensitive to more than one class. The number of taste receptor cells per taste bud ranges from zero to well over 100. A small family of three G-protein-coupled receptors (GPCRs)—T1R1, T1R2, and T1R3—mediate sweet and umami taste sensations. Umami (“savory”) refers to the flavors of meat, cheese, and broth due to glutamate and related compounds. Bitter sensations, in contrast, depend on T2R receptors, a family of ˜30 GPCRs expressed on ...