Source: A Brain-Mind Odyssey, UC Berkeley
Tags: olfaction, olfactory system, smell, nose, olfactory receptor cells, G-protein coupled receptors, GPCR, nasal epithelium, olfactory epithelium, olfactory pseudogenes, cilia, odorant, odour discrimination
Smell begins when odorant molecules enter the nasal passages and reach the olfactory epithelium, where they bind to G-protein coupled receptors (GPCRs) on the cilia of olfactory receptor cells. Humans have about 350 functional olfactory receptor proteins (plus roughly 600 nonfunctional pseudogenes). Odour discrimination works by combinatorial coding: a given odorant activates a particular subset of receptors to varying degrees, producing a unique activation pattern.
Olfactory epithelium (nasal epithelium)
The tissue lining the interior of the nasal passages that contains olfactory receptor cells, stem cells, and structural cells. The site where odorant molecules first contact the sensory system.
Olfactory receptor cells
Neurons in the olfactory epithelium whose cilia are populated by olfactory receptor proteins (GPCRs). They detect odorant molecules and transmit signals to the brain via olfactory nerve fibres.
Cilia (olfactory)
Hair-like projections on olfactory receptor cells that extend into the mucous layer of the nasal epithelium. They carry the GPCR proteins that bind odorant molecules.
G-protein coupled receptors (GPCRs)
The class of receptor protein used in olfaction. Each GPCR responds to molecules with specific molecular shapes. Humans express roughly 350 functional olfactory GPCRs.
Olfactory pseudogenes
Approximately 600 nonfunctional genes in the human genome that are altered so they do not produce functional olfactory receptor proteins. They are remnants of a once-larger olfactory receptor repertoire.
Olfactory stem cells
Stem cells within the nasal epithelium that allow olfactory receptor cells to be regularly replaced. These are not primordial stem cells; they have enough flexibility to differentiate into different types of olfactory receptor cells, but not into any cell type.
Combinatorial odour coding
The principle that a particular odorant molecule differentially activates some subset of olfactory GPCRs to varying extents, producing a unique pattern of receptor activation that the brain reads as a specific smell.
Odorant molecules enter the nasal passages in streams of inhaled and exhaled air.
Molecules are caught in the interior of the nasal passages and reach the nasal epithelium (olfactory epithelium).
From there, molecules travel to the cilia of olfactory receptor cells, which are populated by olfactory receptor proteins (GPCRs).
Signals from activated receptor cells travel along olfactory nerve fibres to the brain.
The olfactory epithelium contains: olfactory receptor cells, structural cells, stem cells, and a mucous layer.
Because olfactory receptor cells are directly exposed to inhaled air (and potentially toxic substances), they are regularly damaged and need replacement.
Stem cells in the nasal epithelium provide this replacement capacity. These stem cells are not primordial (they cannot become any cell type), but they are flexible enough to differentiate into the various types of olfactory receptor cells.
Olfactory receptors belong to the G-protein coupled receptor (GPCR) family.
Humans have roughly 350 functional olfactory receptor proteins, each tuned to molecules of specific molecular shapes.
An additional ~600 olfactory pseudogenes exist in the genome. These are nonfunctional, altered so they do not produce working receptor proteins.
Odour discrimination relies on combinatorial coding: a given odorant molecule activates a particular subset of the 350 olfactory GPCRs, each to varying degrees.
The unique pattern of activation across many receptor types is what the brain interprets as a distinct smell.
This combinatorial approach allows a relatively small number of receptor types to distinguish a vast number of different odorants.
⚠️ Know the pathway: odorant → nasal passages → olfactory epithelium → cilia → GPCR binding → olfactory nerve fibres → brain.
⚠️ Olfactory receptors are GPCRs. This receptor class is a recurring concept across neuroscience.
⚠️ 350 functional olfactory receptors vs. ~600 pseudogenes. The pseudogenes are a common exam detail.
⚠️ Olfactory stem cells are not primordial. They can become different types of olfactory receptor cells, but they are not capable of becoming any cell type.
⚠️ Combinatorial coding is the mechanism for odour discrimination. A single odorant activates multiple receptor types to varying degrees; the pattern, not a single receptor, encodes the smell.
Q: Describe the pathway by which an odorant molecule leads to a smell perception.
A: Odorant molecules enter the nasal passages via inhaled/exhaled air, reach the olfactory epithelium, and bind to GPCR proteins on the cilia of olfactory receptor cells. The activated receptor cells send signals along olfactory nerve fibres to the brain, where the pattern of activation is interpreted as a specific smell.
Q: Why do olfactory receptor cells need to be regularly replaced?
A: They are directly exposed to inhaled air, which can contain toxic substances that damage the cells. Stem cells in the nasal epithelium provide replacements.
Q: How can roughly 350 receptor types distinguish thousands of different odours?
A: Through combinatorial coding. Each odorant differentially activates a subset of the 350 GPCRs to varying extents, creating a unique activation pattern that the brain reads as a distinct smell.
Q: What are olfactory pseudogenes?
A: Approximately 600 nonfunctional genes in the human genome that are altered versions of olfactory receptor genes. They do not produce working receptor proteins.
Q: How do olfactory stem cells differ from embryonic (primordial) stem cells?
A: Olfactory stem cells can differentiate into different types of olfactory receptor cells, but they cannot become any cell type. Embryonic stem cells have broader differentiation potential.
olfaction, olfactory system, smell, nose, nasal passages, nasal epithelium, olfactory epithelium, olfactory receptor cells, cilia, mucous layer, G-protein coupled receptor, GPCR, odorant, olfactory pseudogenes, olfactory stem cells, combinatorial coding, odour discrimination, olfactory nerve fibres, molecular shape, neurotrophin, receptor protein, signal transduction