Premed · Premed · Anatomy Physiology 1
Lecture 23: Special Senses — Taste and Smell
Anatomy and Physiology I
Learning Objectives
By the end of this lecture, students will be able to:
- Describe the anatomy of the olfactory epithelium and identify the cell types involved in olfaction
- Explain the mechanism of olfactory transduction and the encoding of odor information
- Trace the olfactory pathway from receptor to cortex and explain why olfaction has strong links to emotion and memory
- Describe the types of taste buds and papillae and their distribution on the tongue
- Explain the mechanism of gustatory transduction for each of the five basic tastes
- Trace the gustatory pathway from receptor to cortex
- Explain how taste and smell interact to produce the perception of flavor
Lecture Content
I. Olfaction — The Sense of Smell
Olfactory Epithelium
The olfactory epithelium is located on the roof of the nasal cavity, covering the superior nasal conchae and the adjacent nasal septum, with a total area of approximately 5 square centimeters in humans (much larger in other mammals). It contains three cell types.
Olfactory receptor neurons (ORNs) are bipolar neurons that hold the distinction of being the only neurons in the body directly exposed to the external environment while also being regularly replaced, with turnover occurring approximately every 30-60 days from basal cells. Each ORN extends a dendrite to the epithelial surface ending in a knob that bears 10-20 olfactory cilia, which serve as the site of odorant detection. Remarkably, each ORN expresses only one type of odorant receptor gene out of approximately 400 functional receptor genes in humans, each encoding a receptor for a different molecular feature. The axons of ORNs are very thin, unmyelinated fibers (fila olfactoria) that pass through the cribriform plate of the ethmoid bone to reach the olfactory bulb. Supporting (sustentacular) cells provide structural and metabolic support, detoxify chemicals, and produce mucus. Basal cells are stem cells that divide to replace olfactory receptor neurons throughout life, representing one of the few examples of neurogenesis in the adult nervous system.
Olfactory (Bowman) glands in the lamina propria secrete mucus that coats the epithelial surface. Odorant molecules must dissolve in this mucus layer before they can bind to receptors on the olfactory cilia. Odorant-binding proteins (OBPs) in the mucus help transport hydrophobic odorants to the receptors.
Olfactory Transduction
Olfactory transduction proceeds through a well-characterized signaling cascade. Odorant molecules first dissolve in the mucus layer covering the olfactory epithelium. The odorant then binds to a specific odorant receptor, which is a G-protein-coupled receptor (GPCR), on the cilia of an ORN. This activates a G-protein called Golf (an olfactory-specific G-protein), which in turn activates adenylyl cyclase, converting ATP to cAMP. The cAMP opens cyclic nucleotide-gated (CNG) cation channels on the cilia membrane, allowing sodium and calcium to flow into the cell and causing depolarization (the receptor potential). The calcium influx additionally opens calcium-activated chloride channels, and because ORNs maintain unusually high intracellular chloride, chloride flows out of the cell, further depolarizing it. If the receptor potential reaches threshold, action potentials are generated and propagated along the ORN axon to the olfactory bulb.
Odor Encoding
Humans can discriminate an estimated one trillion different odors through combinatorial coding. Each odorant activates a specific combination of receptor types, and the brain interprets the pattern of activated receptors as a specific odor. A single odorant molecule may activate multiple receptor types, and conversely, a single receptor type may respond to multiple related odorants. The unique combination creates a distinct "odor code." Odor intensity is encoded by the number of ORNs activated and the frequency of their action potentials.
Olfactory Adaptation
Rapid adaptation to sustained odors explains why you stop noticing a smell within minutes. This adaptation occurs at multiple levels: at the receptor level through cAMP-mediated feedback that reduces CNG channel sensitivity, through decreased neurotransmitter release, and through central habituation in cortical processing.
II. Olfactory Pathway
The olfactory pathway begins with ORN axons passing through the cribriform plate as the olfactory fila, collectively constituting CN I. They reach the olfactory bulb, which is located on the inferior surface of the frontal lobe and rests on the cribriform plate. Within the olfactory bulb, ORN axons synapse in spherical structures called glomeruli. Each glomerulus receives input exclusively from ORNs expressing the same receptor type, providing convergence that amplifies the signal and creates an odor map. Mitral cells and tufted cells are the main output neurons of the olfactory bulb, with their axons forming the olfactory tract. Periglomerular cells and granule cells serve as interneurons providing lateral inhibition that sharpens odor discrimination.
The olfactory tract carries information to several brain regions: the primary olfactory cortex (piriform cortex) in the temporal lobe for conscious perception of odor; the amygdala for emotional responses to odors such as fear, pleasure, and aversion; the entorhinal cortex for links to the hippocampus and olfactory memory; the orbitofrontal cortex for odor identification, discrimination, and hedonic evaluation (received after a thalamic relay); and the hypothalamus for autonomic and feeding responses to odors.
Unique Features of the Olfactory Pathway
Olfaction is the only sensory system that reaches the cortex without a thalamic relay at the primary cortex level (though the thalamus is involved in higher-order processing via the orbitofrontal cortex). Its direct connections to the limbic system, including the amygdala and hippocampus, explain why odors are powerful triggers of emotional memories. The smell of a specific food evoking a vivid childhood memory, sometimes called the "Proust phenomenon," exemplifies this unique limbic connection.
<image>A midsagittal view of the nasal cavity and brain showing the olfactory pathway. The olfactory epithelium is shown on the roof of the nasal cavity with olfactory receptor neurons (ORNs) depicted with their cilia extending into the mucus layer. Thin axons of the ORNs pass through the cribriform plate of the ethmoid bone (labeled) to enter the olfactory bulb. Within the olfactory bulb, glomeruli are shown as spherical structures where ORN axons synapse on mitral cells. All ORNs of the same receptor type converge on the same glomerulus (color-coded: e.g., green ORNs to green glomerulus, blue ORNs to blue glomerulus). Mitral cell axons form the olfactory tract, which projects to the primary olfactory cortex (piriform cortex in the temporal lobe), the amygdala, the entorhinal cortex (with an arrow to the hippocampus), and the orbitofrontal cortex (via a thalamic relay). A zoomed inset of the olfactory epithelium shows the three cell types: olfactory receptor neurons with cilia, supporting cells, and basal cells, plus Bowman glands secreting mucus. The transduction cascade is summarized in a small flow chart: odorant binds receptor, Golf activates adenylyl cyclase, cAMP opens CNG channels, Na+/Ca2+ influx causes depolarization.</image>
III. Gustation — The Sense of Taste
Taste Buds and Papillae
The tongue contains approximately 10,000 taste buds in the average adult, located primarily on the tongue but also on the soft palate, pharynx, and epiglottis. Each taste bud is an oval structure containing 50-100 cells of three types. Gustatory (taste) receptor cells are modified epithelial cells (not neurons) that have gustatory microvilli (taste hairs) protruding through a taste pore at the epithelial surface; these microvilli are the site of tastant detection. Supporting cells provide structural support, and basal cells serve as stem cells that replace taste receptor cells every 7-10 days.
Taste buds are housed within papillae on the tongue surface. Circumvallate (vallate) papillae are 7-12 large, dome-shaped structures arranged in a V-shape at the back of the tongue, with each containing 100-300 taste buds, making them the largest papillae. Fungiform papillae are mushroom-shaped structures scattered over the anterior two-thirds of the tongue, each containing approximately 3-5 taste buds along with tactile and temperature receptors. Foliate papillae are leaf-shaped folds on the posterolateral tongue margins containing many taste buds, and they are more prominent in children. Filiform papillae are the most numerous type: small, pointed, cone-shaped projections covering the entire tongue surface that provide friction for food manipulation but contain no taste buds and therefore play no role in taste perception.
It is important to note that the old "tongue map" depicting specific regions for each taste is incorrect. All taste qualities can be detected across the entire tongue, although sensitivity varies slightly by region.
The Five Basic Tastes
Sweet taste is elicited by sugars, some amino acids, and artificial sweeteners, signaling energy-rich carbohydrate foods. Transduction involves the tastant binding to the T1R2/T1R3 heterodimer (a GPCR), which activates gustducin (a G-protein) and the phospholipase C/IP3 cascade, leading to calcium release from intracellular stores. This calcium triggers ATP release through pannexin channels, and the ATP activates purinergic receptors on afferent nerve fibers.
Salty taste is produced by sodium chloride and other salts, signaling electrolyte balance. Its transduction is the most direct: sodium enters the cell through ENaC (epithelial sodium channels) on the apical surface, depolarizing the cell, opening voltage-gated calcium channels, and triggering neurotransmitter release.
Sour taste is produced by acids (hydrogen ions) and signals potentially spoiled food or unripe fruit. Hydrogen ions enter through Otop1 proton channels and also block potassium channels; both actions depolarize the cell.
Bitter taste is triggered by alkaloids and toxins such as caffeine, quinine, and strychnine, signaling potentially toxic substances and triggering a rejection or spitting response. Tastants bind to T2R receptors (GPCRs), of which there are approximately 25 different genes detecting different bitter compounds. This activates gustducin and the same phospholipase C/IP3 cascade used by sweet taste. The existence of many different bitter receptors explains our remarkable sensitivity to a wide variety of bitter compounds.
Umami is the savory taste associated with glutamate, aspartate, and protein-rich foods such as meat, cheese, mushrooms, and MSG, signaling protein and amino acid content. Glutamate binds to the T1R1/T1R3 heterodimer (a GPCR), and the downstream cascade is the same as for sweet and bitter.
Additional Oral Sensations
Several oral sensations are often confused with taste but involve distinct mechanisms. Spiciness and heat are not true tastes; capsaicin from chili peppers activates TRPV1 nociceptors that are normally sensitive to heat. Similarly, the cooling sensation from menthol activates TRPM8 cold receptors. Astringency, experienced with tannins in tea and wine, results from protein precipitation creating a drying sensation. Emerging evidence supports a possible sixth basic taste for fat (oleogustus), mediated by fatty acid receptors (CD36 and GPR120) on taste cells. Kokumi, involving calcium-sensing receptor (CaSR) activation that enhances richness and continuity of taste, is not yet universally accepted as a basic taste.
<image>An anatomical diagram of the tongue showing taste-related structures. Panel A: A dorsal view of the tongue showing the distribution of the four types of papillae. Circumvallate papillae are arranged in a V-shape near the posterior tongue (7-12 large dome shapes). Fungiform papillae are scattered as small red dots over the anterior two-thirds. Foliate papillae appear as parallel folds on the posterolateral margins. Filiform papillae cover the entire surface as small pointed projections. The sulcus terminalis (V-shaped groove) separates the anterior 2/3 from the posterior 1/3. Panel B: A cross-section through a circumvallate papilla showing taste buds embedded in the lateral walls of the trench surrounding the papilla. Panel C: An enlarged view of a single taste bud showing gustatory receptor cells with microvilli (taste hairs) extending through the taste pore, supporting cells, basal cells at the base, and afferent nerve fibers entering from below. Panel D: A summary diagram of the five transduction mechanisms side by side — sweet (T1R2/T1R3 GPCR pathway), salty (ENaC sodium channel), sour (Otop1 proton channel and K+ channel block), bitter (T2R GPCR pathway), and umami (T1R1/T1R3 GPCR pathway). Each mechanism shows the key receptor/channel, the transduction cascade, and the final result of neurotransmitter release.</image>
IV. Gustatory Pathway
The gustatory pathway begins when taste receptor cells release neurotransmitter (ATP) onto afferent nerve fibers. Three cranial nerves carry taste information from different regions: CN VII (facial nerve, chorda tympani branch) from the anterior two-thirds of the tongue, CN IX (glossopharyngeal nerve) from the posterior one-third of the tongue, and CN X (vagus nerve) from the epiglottis and pharynx. All three nerves converge on the nucleus of the solitary tract (gustatory nucleus) in the medulla. Second-order neurons project to the ventral posteromedial (VPM) nucleus of the thalamus, and third-order neurons continue to the primary gustatory cortex located in the insula and the frontal operculum (Brodmann area 43). Information is also relayed to the orbitofrontal cortex for conscious flavor perception and hedonic evaluation, and to the hypothalamus and amygdala for autonomic responses such as salivation and gastric secretion, as well as emotional and learned responses to food including conditioned taste aversion.
V. Integration of Taste and Smell — Flavor Perception
Flavor is a multimodal perception that combines several sensory inputs. Taste (gustation) provides the five basic taste qualities from the taste buds. Smell (olfaction) contributes the aroma of food, especially via retronasal olfaction, in which volatiles from food in the mouth travel up through the nasopharynx to the olfactory epithelium during chewing and swallowing. Somatosensation provides information about texture (mechanoreceptors), temperature (thermoreceptors), and spiciness or irritation (nociceptors and TRPV1). Vision contributes food appearance and color.
Olfaction contributes the majority of what we perceive as "taste," which is why food tastes bland during a cold when nasal congestion blocks odorant access to the olfactory epithelium. Approximately 80% of what we commonly call "taste" is actually smell. Integration of these multiple sensory streams occurs primarily in the orbitofrontal cortex and insula, which receive converging input from gustatory, olfactory, somatosensory, and visual areas.
VI. Age-Related Changes
Both chemical senses decline with aging, though at different rates. For olfaction, a gradual decline begins around age 50 with more rapid decline after age 70, driven by reduced numbers of ORNs, decreased mucus production, and slower regeneration from basal cells. This decline contributes to decreased appetite and nutritional risk in the elderly and can also serve as an early sign of neurodegenerative disease such as Parkinson disease or Alzheimer disease.
Gustation is less affected by aging than olfaction. There is some decrease in the number of taste buds and reduced sensitivity, especially for salty and bitter tastes. Many older adults perceive food as tasteless, but this is mostly attributable to olfactory decline rather than gustatory decline. Medications such as ACE inhibitors and metformin can also alter taste perception.
VII. Clinical Correlations
Olfactory Disorders
Anosmia is the complete loss of smell, with causes including head trauma (shearing of olfactory fila at the cribriform plate), upper respiratory infection, nasal polyps, neurodegenerative disease (Parkinson and Alzheimer), and COVID-19. Hyposmia is a reduced sense of smell caused by aging, smoking, or nasal congestion. Parosmia is distorted smell perception, such as pleasant odors perceived as foul, which can occur during recovery from anosmia. Phantosmia is smelling an odor that is not present (an olfactory hallucination) and can be caused by temporal lobe seizures, migraines, or psychiatric conditions.
Gustatory Disorders
Ageusia is the complete loss of taste, which is rare because three different nerves serve taste. Hypogeusia is reduced taste caused by zinc deficiency, medications, radiation therapy to the head and neck, or aging. Dysgeusia is distorted taste perception, often a metallic or unpleasant taste, and is common with certain medications such as metronidazole and captopril.
Cribriform Plate Fracture
Trauma to the anterior cranial fossa can fracture the cribriform plate, carrying risks of anosmia (from torn olfactory fila), CSF rhinorrhea (cerebrospinal fluid leaking through the nose), and meningitis (bacteria entering the cranial cavity through the damaged plate).
