Source: MCB C61, UC Berkeley, Ch. 12–13
Tags: olfactory bulb, olfactory receptor cells, cilia, olfactory stem cells, olfactory receptor proteins, GPCR, anosmia, pheromones, vomeronasal organ, taste buds, gustatory receptor cells, microvilli, salt, sour, bitter, sweet, umami, ion channels, TRP channels, capsaicin, TRPV1, menthol, TRPM8, isothiocyanates, TRPA1, miraculin, aspartame, stevia, George Berkeley, immaterialism
Smell and taste are both chemical senses, but they work through very different receptor systems. Olfaction uses ~350 GPCR types in the nasal epithelium to detect around 100,000 different smells via combinatorial coding. Taste uses five categories of receptor cells (salt, sour, bitter, sweet, umami) that rely on a mix of ion channels and GPCRs. Pungency (chilli heat, mint coolness, wasabi burn) is separate from taste proper and is detected by TRP channel receptors found throughout the body.
Olfactory receptor cells
Neurons in the nasal epithelium with cilia at their dendritic ends that make first contact with odorant molecules. Their axons project into the olfactory bulb.
Cilia (olfactory)
Small hair-like extensions of the dendrites of olfactory receptor cells. They protrude from the mucous layer in the nose and contain olfactory receptor proteins. The site of first interaction with odorants.
Olfactory receptor proteins
GPCRs embedded in the cilia of olfactory receptor cells. Humans have ~350 functional olfactory receptor genes (plus ~600 pseudogenes that no longer code for functional proteins). Each receptor responds to a specific molecular shape, but combinatorial activation allows detection of ~100,000 different smells.
Olfactory bulb
The brain structure where axons from olfactory receptor cells synapse with dendrites of mitral cells, beginning the signalling pathway to the brain.
Olfactory nerve fibres
Cranial nerve 1 (CN I). The connections between the nose and the olfactory bulb, formed by axons from olfactory receptor cells.
Olfactory stem cells
Cells in the nasal epithelium that can differentiate into various types of olfactory receptor cells. They replace olfactory receptor cells every 1–2 months, which is necessary because direct exposure to environmental toxins causes continual cellular damage.
Anosmia (specific)
Loss of sensitivity to a specific smell. Most likely caused by genetic variation in one of the ~350 olfactory GPCRs. Example: some people cannot smell the sulphury odour of asparagus metabolites in urine.
Anosmia (general)
Loss of sensitivity to broad categories of aroma. Causes include nasal congestion, developmental factors, head trauma, and degenerative brain disease.
Hyperosmia
Increased sensitivity to odours. Sometimes occurs during pregnancy.
Pheromones
Chemicals that carry signal information for social communication between members of the same species. Used by insects for identity, social status, trail marking, mating, and danger signalling. In humans, possible roles include menstrual synchrony, sexual attraction (linked to human leukocyte antigen genes), and bonding behaviours triggered by tears.
Vomeronasal organ
A distinct olfactory sensory structure in vertebrate animals with a neural pathway that responds somewhat selectively to pheromone signals.
George Berkeley (Bishop Berkeley)
Irish philosopher who advanced immaterialism: the view that material substance does not exist independently, and familiar objects are only ideas in the mind of perceivers. The University of California, Berkeley is named after him.
Taste vs. flavour
Taste is the sense inside the mouth (salt, sour, bitter, sweet, umami). Flavour is the combination of taste, smell (aromatic molecules via the olfactory system), texture, and pungency.
Taste buds
Approximately 10,000 in the human mouth, each containing around 100 taste receptor cells. Clusters of bulbous nerve endings on the tongue and mouth lining.
Gustatory receptor cells
Located primarily on the tongue, with some on the upper palate and pharynx. About one million total in the mouth. Their ends are composed of microvilli (which increase surface area), and within the microvilli membranes are taste receptor proteins. At the base of each cell, a chemical synapse connects with cranial nerve fibres (CN 7, 9, 10) that carry signals to the brain.
Microvilli
Filamentous structures at the tips of gustatory receptor cells that increase the surface area exposed to dissolved food and drink molecules.
Gustatory stem cells
Similar to olfactory stem cells, they differentiate into various types of taste receptor cells, allowing replacement approximately every 2 weeks. Necessary because taste receptor cells are constantly exposed to damaging environmental substances.
Capsaicin
The molecule in chilli peppers (Capsicum annuum) that produces the sensation of heat. Binds to TRPV1, an ionotropic TRP channel receptor that also responds to thermal heat (43–50°C). The sensation of chilli heat and fire heat are the same quality in perception.
TRPV1
A TRP channel receptor whose ion channel opens in response to capsaicin, piperine (black pepper), and heat in the 43–50°C range. Found throughout the body.
Menthol
A compound from mint plants that produces the perception of coolness. Binds to TRPM8, a TRP channel receptor that also responds to temperatures cooler than body temperature.
TRPM8
The TRP channel receptor for menthol and cool temperatures.
Isothiocyanates
Pungent compounds found in mustard, horseradish, and wasabi. A configuration of sulphur, carbon, and nitrogen atoms. Bind to TRPA1.
TRPA1
The TRP channel receptor activated by isothiocyanates (mustard, horseradish, wasabi).
TRP channels (transient receptor potential)
A large family of ionotropic receptor proteins found throughout the body (mouth, skin, nervous system). They open calcium ion channels in response to specific chemical ligands or temperature ranges.
Miraculin
A glycoprotein from the fruit of Synsepalum dulcificum (miracle fruit). Not sweet itself, but after binding to sweet receptors on the tongue, it causes acidic (sour) foods to be perceived as sweet. It only activates the sweet receptor in a sour environment.
Stevia
A non-nutritive sweetener from the plant Stevia rebaudiana, native to the Amazon. The sweet leaves are dehydrated and marketed as a sugar substitute.
Delbrück's Principle of Limited Sloppiness
Describes unexpected discoveries made because a scientist was slightly sloppy, but not so sloppy they couldn't figure out what happened. Explains how aspartame was discovered by accident.
The pathway from nose to brain:
Odorant molecules contact cilia in the nasal mucous layer
Cilia contain olfactory receptor proteins (GPCRs) that respond to specific molecular shapes
Activated receptor cells send axons into the olfactory bulb, where they synapse with mitral cells
Mitral cells project to the pyriform cortex and amygdala
Amygdala signals the temporal cortex and hypothalamus
Pyriform cortex signals the thalamus, which signals the orbitofrontal cortex of the frontal lobe
Combinatorial coding:
Humans have ~350 functional olfactory receptor genes
~600 additional pseudogenes exist but no longer produce functional proteins (lost evolutionarily)
Each odorant molecule differentially activates a subset of the 350 receptor types
This combinatorial mechanism allows detection of ~100,000 distinct smells
Cross-species comparison of olfactory receptor genes:
Fish: ~100 genes
Humans: ~350 genes
Mammals (typical): ~1,000 genes
Mouse: ~1,300 genes
Receptor cell turnover:
Olfactory stem cells in the nasal epithelium replace receptor cells every 1–2 months
Direct exposure to environmental toxins causes continual damage; this turnover is the cost of chemoreception
Aromas and their molecular basis:
Plant aromas are mixtures of dozens of different molecules that activate various combinations of receptor proteins
Sulphur-containing compounds (thiols, with an -SH group) tend to smell unpleasant because their shape fits into many GPCRs
Spices like cinnamon (cinnamaldehyde, eugenol, ethyl cinnamate) and cardamom (limonene, menthone, eucalyptol) derive their distinctive aromas from specific chemical compounds
Pheromones elicit innately programmed behaviours or biochemical changes: suckling in young mammals, hormone regulation in mating, aspects of attraction and aggression
Human pheromone effects (less well established): menstrual synchrony, sexual attraction linked to HLA genes, bonding behaviours triggered by tears
The vomeronasal organ is a dedicated olfactory structure in vertebrates with some selectivity for pheromone signals
Salt
Receptor proteins are thought to be ion channels that allow sodium ions to flow across the membrane, triggering a neural signal
Ingestion of sodium and related cations (potassium, calcium, magnesium) is essential for survival
Moderate saltiness is generally perceived as pleasant
Sour
Detects acids: the release of hydrogen ions (H+) through channels
Sources: citric acid (grapefruit, lemon), acetic acid (vinegar), lactic acid (sauerkraut, yoghurt)
High H+ concentrations cause positive charge to flow through channels in sour taste receptor cells
Bitter
Uses GPCRs, not ion channels
More than 30 different GPCR proteins are distributed across bitter taste receptor cells
Ligand binding initiates an intracellular signalling cascade leading to NT release
The diversity of GPCRs allows many different molecular shapes to register as bitter
Examples of bitter compounds: plant alkaloids such as caffeine, cocaine, morphine, quinine
Bitter taste may serve as a poison warning, though it can be appreciated in combination with other tastes (dark chocolate, tea, leafy vegetables)
Sweet
Uses GPCRs, not ion channels
Two distinct GPCRs involved; the functional receptor is a dimer of two GPCRs
Sugar molecules (sucrose, glucose, fructose, lactose, maltose) bind as ligands
Sweetness is generally perceived as pleasurable; few sweet things exist in nature (mainly ripe fruits)
Synthetic sweeteners: saccharin (~300x sweeter than sucrose, also slightly bitter), cyclamate (1930s), aspartame (1960s, discovered by accident), sucralose/Splenda (~600x sweeter, 3 hydroxyl groups replaced by chlorine)
Stevia: plant-derived non-nutritive sweetener
Miraculin: a taste modifier that makes sour foods taste sweet after binding to sweet receptors
Umami
Described by Kikunae Ikeda in 1909; "savoury," "meaty," "mushroomy"
Detected by a fifth type of taste receptor cell using GPCRs that respond to glutamate and other amino acids
Glutamate is an amino acid that makes up proteins; umami receptors likely evolved to detect protein-containing foods
MSG (monosodium glutamate) concentrates the umami taste for use in cooking
This is a fundamental distinction. Salt and sour detection involves direct ion flow through channel proteins. Bitter, sweet, and umami detection involves GPCR-mediated intracellular signalling cascades.
Pungency signals enter the brain via cranial nerve 5 and are received by pain-associated brain regions, separate from the primary taste pathways.
TRPV1: capsaicin (chilli) and heat (43–50°C), also piperine (black pepper). Calcium ion channel.
TRPM8: menthol (mint) and cool temperatures. Calcium ion channel.
TRPA1: isothiocyanates (mustard, horseradish, wasabi). Calcium ion channel.
All are members of the TRP receptor family, found throughout the body
Gustatory stem cells replace taste receptor cells approximately every 2 weeks
This mirrors the olfactory system's turnover and is driven by the same logic: constant exposure to potentially damaging substances
This regular replacement distinguishes taste and smell from vision and hearing, where receptor cells are not readily replaced
⚠️ Know the distinction: salt and sour use ion channels; bitter, sweet, and umami use GPCRs.
⚠️ Humans have ~350 functional olfactory receptor genes but can detect ~100,000 smells through combinatorial activation.
⚠️ Sweet taste receptors function as GPCR dimers (two GPCRs together form the functional unit).
⚠️ Pungency (capsaicin, menthol, wasabi) is not a taste. It enters the brain via CN 5 (trigeminal), not the taste cranial nerves (CN 7, 9, 10).
⚠️ TRPV1 responds to both capsaicin and thermal heat. Chilli-hot and fire-hot are the same quality in our perception.
⚠️ Both olfactory and gustatory receptor cells are regularly replaced by stem cells (1–2 months for smell, ~2 weeks for taste). Visual and auditory receptors are not replaced this way.
⚠️ The olfactory pathway bypasses the thalamus initially (going to pyriform cortex and amygdala first), unlike most other sensory pathways.
Q: How can humans detect ~100,000 different smells with only ~350 olfactory receptor types?
A: Each odorant molecule differentially activates a subset of the 350 receptor types. The unique combination of activated receptors encodes a distinct smell (combinatorial coding).
Q: What is the functional receptor unit for sweet taste?
A: A dimer of two GPCRs. Two distinct GPCR proteins come together to form the functional sweet taste receptor.
Q: Why are capsaicin (chilli) and thermal heat perceived as the same sensation?
A: Both activate the same receptor, TRPV1. This TRP channel opens in response to capsaicin binding and also to temperatures in the 43–50°C range.
Q: Through which cranial nerve does pungency information reach the brain, and how does this differ from taste?
A: Pungency travels via cranial nerve 5 (trigeminal) to pain-associated brain regions. Taste travels via cranial nerves 7, 9, and 10.
Q: Why do olfactory and gustatory receptor cells need regular replacement?
A: They are directly exposed to environmental substances, including potentially toxic chemicals, which causes continual cellular damage. Stem cells in the nasal epithelium and on the tongue replace them every 1–2 months (smell) and ~2 weeks (taste).
Q: What is the olfactory signalling pathway from nose to cortex?
A: Odorants bind GPCRs on cilia → olfactory receptor cells fire → axons synapse with mitral cells in olfactory bulb → mitral cells project to pyriform cortex and amygdala → amygdala signals temporal cortex and hypothalamus; pyriform cortex signals thalamus → thalamus signals orbitofrontal cortex.
Q: Which taste categories use GPCRs, and which use ion channels?
A: Bitter, sweet, and umami use GPCRs. Salt and sour use ion channels.
Q: What is miraculin, and how does it work?
A: A glycoprotein from miracle fruit that binds to sweet taste receptors but only activates them in an acidic (sour) environment, causing sour foods to taste sweet.
olfaction, olfactory receptor cells, cilia, olfactory receptor proteins, GPCR, olfactory bulb, mitral cells, olfactory nerve, cranial nerve 1, olfactory stem cells, combinatorial coding, anosmia, specific anosmia, general anosmia, hyperosmia, pheromones, vomeronasal organ, HLA genes, menstrual synchrony, pyriform cortex, amygdala, orbitofrontal cortex, thalamus, thiols, sulphur, spice chemistry, George Berkeley, immaterialism, taste, flavour, taste buds, gustatory receptor cells, microvilli, gustatory stem cells, cranial nerves 7 9 10, salt, sour, bitter, sweet, umami, ion channel, GPCR dimer, saccharin, aspartame, sucralose, Splenda, stevia, miraculin, miracle fruit, Delbrück, limited sloppiness, capsaicin, Capsicum annuum, TRPV1, menthol, TRPM8, isothiocyanate, wasabi, mustard, TRPA1, TRP channels, transient receptor potential, pungency, cranial nerve 5, Kikunae Ikeda, MSG, glutamate