Physiology of Smell: Olfactory Receptors, Pathway and Disorders
Olfaction is the special sense that detects airborne chemical molecules and allows the brain to recognise odours. Odorants dissolve in mucus over the olfactory epithelium, bind to receptors on olfactory sensory neurons and are converted into electrical signals that travel through the olfactory bulb to cortical and limbic areas.
Smell contributes greatly to flavour, appetite, memory, emotion and recognition of environmental hazards such as smoke, spoiled food and leaking fuel. A patient who reports “loss of taste” often has reduced smell and can still identify the basic tastes on the tongue.
Odorant → olfactory receptor → receptor potential → CN I fibres → olfactory bulb → olfactory tract → cortex and limbic system. Each stage can be disturbed by nasal obstruction, epithelial injury, shearing of nerve fibres, bulb damage or central nervous-system disease.
Learning objectives
- Describe the olfactory epithelium and its principal cell types.
- Explain how an odorant is converted into an action potential.
- Trace the olfactory pathway from the nasal cavity to the brain.
- Explain odour coding, discrimination and adaptation.
- Relate smell to taste, flavour, emotion and memory.
- Outline clinical smell testing and common olfactory disorders.
Olfactory region
The olfactory epithelium occupies a small specialised region high in each nasal cavity, principally over the superior nasal concha, upper nasal septum and adjacent roof. Review the anatomy of the nose and nasal cavity to understand its relation to the cribriform plate and anterior cranial fossa.
A bipolar primary sensory neuron. Its apical dendrite ends in a knob bearing non-motile cilia with odorant receptors; its basal axon contributes to CN I.
Provides metabolic and physical support, helps maintain the local chemical environment and assists detoxification of inhaled substances.
Acts as a progenitor cell that can generate new receptor and supporting cells, giving the olfactory epithelium some regenerative capacity.
Produces serous fluid that contributes to olfactory mucus, dissolves odorants and helps clear previously detected molecules.
The receptor neurons are unusual because they are exposed to the external environment yet connect directly with the brain. Their axons group into multiple small olfactory nerve bundles that pass through foramina in the cribriform plate.
Requirements for an odorant
For a substance to be smelled efficiently, molecules must reach the olfactory region and interact with receptor proteins. Important properties include:
- Volatility: molecules must enter the air so they can be inhaled.
- Solubility: odorants must dissolve sufficiently in olfactory mucus.
- Access: nasal airflow must carry molecules toward the superior cavity.
- Receptor compatibility: the molecule or its features must activate one or more receptor types.
- Adequate concentration: enough molecules must be present to exceed the detection threshold.
Two routes to the receptors
| Route | Direction | Importance |
|---|---|---|
| Orthonasal olfaction | Odorants enter through the nostrils during sniffing or normal inspiration. | Detects smells in the external environment. |
| Retronasal olfaction | Volatile molecules from food move from the mouth and pharynx into the nasal cavity during chewing and swallowing. | Produces much of the complex perception called flavour. |
Nasal congestion reduces access of odorants to the epithelium. This is why food may seem tasteless during a severe cold even when tongue taste receptors remain functional.
Olfactory transduction
Transduction is the conversion of odorant binding into an electrical response. The principal mammalian pathway occurs in the membrane of olfactory cilia.
- Odorant binding: an odorant dissolves in mucus and binds to a G-protein-coupled receptor on an olfactory cilium.
- G-protein activation: the receptor activates the specialised olfactory G protein, commonly called Golf.
- Second messenger formation: Golf stimulates adenylyl cyclase III, which increases intracellular cyclic AMP.
- Cation-channel opening: cyclic AMP opens cyclic-nucleotide-gated channels, allowing sodium and calcium to enter.
- Signal amplification: the rise in calcium opens calcium-activated chloride channels. Chloride exits the neuron, increasing depolarisation because olfactory neurons maintain a relatively high intracellular chloride concentration.
- Action potentials: if the receptor potential reaches threshold, action potentials travel along the neuron’s axon toward the olfactory bulb.
Receptor → Golf → adenylyl cyclase → cyclic AMP → cation channels → depolarisation → action potentials.
Olfactory nerve and bulb
The unmyelinated axons of receptor neurons assemble into small bundles called olfactory fila. They pass through the cribriform plate as the olfactory nerve, cranial nerve I, and enter the olfactory bulb.
Glomerular organisation
Within the bulb, receptor axons end in spherical synaptic structures called glomeruli. Neurons expressing the same receptor type tend to converge on specific glomeruli. This convergence increases sensitivity and helps create an organised map of receptor activity.
Receptor neurons synapse mainly with:
- Mitral cells: major output neurons of the bulb.
- Tufted cells: additional output neurons that carry processed information.
- Periglomerular and granule cells: local inhibitory interneurons that sharpen contrast, shape timing and help distinguish related odours.
Central olfactory pathway
| Stage | Structure | Main role |
|---|---|---|
| First-order neuron | Olfactory sensory neuron in the nasal epithelium. | Detects odorants and sends axons through the cribriform plate. |
| First synapse | Glomerulus in the olfactory bulb. | Organises, amplifies and refines receptor input. |
| Bulb output | Mitral and tufted cells forming the olfactory tract. | Carries processed information posteriorly. |
| Primary olfactory areas | Piriform cortex, amygdala and entorhinal region. | Odour perception, emotional significance and association with memory. |
| Higher integration | Orbitofrontal cortex and connected networks. | Conscious identification, discrimination and integration with taste and other senses. |
Olfaction is distinctive because primary input reaches olfactory cortex without first making the obligatory thalamic relay typical of other sensory systems. Higher conscious discrimination in orbitofrontal cortex does involve thalamic connections.
Direct links with the amygdala, hippocampal system, hypothalamus and other limbic structures explain why a smell can rapidly evoke emotion, appetite, autonomic responses and vivid memories.
How the brain identifies many odours
Humans do not require one receptor for every possible smell. Instead, olfactory coding is combinatorial:
- Each receptor type can respond to several odorants with different sensitivities.
- Each odorant can activate several receptor types.
- The brain interprets the resulting spatial and temporal pattern across many glomeruli.
- Concentration changes the strength, timing and spread of neuronal activity, so the same chemical may smell different at high concentration.
- Learning and previous experience help assign identity, pleasantness and significance.
This population code allows discrimination of a very large number of odours from a more limited receptor repertoire.
Threshold, sniffing and adaptation
Detection and recognition thresholds
The detection threshold is the lowest concentration at which a person notices that an odour is present. The recognition threshold is usually higher and is the concentration at which the odour can be identified. Thresholds vary between individuals and with age, attention, genetics, disease and environmental exposure.
Role of sniffing
Sniffing creates airflow patterns that deliver a larger, more controlled sample toward the olfactory cleft. It also coordinates nasal input with respiratory and brain activity, improving detection and discrimination.
Olfactory adaptation
During continuous exposure, perceived intensity falls even though the odorant remains. Adaptation occurs at several levels:
- Calcium-dependent processes reduce receptor-neuron responsiveness.
- Intracellular signalling and receptor mechanisms become less sensitive.
- Inhibitory circuits in the bulb and central nervous system reduce the response.
- Attention shifts away from an unchanging, non-threatening stimulus.
Adaptation prevents constant background smells from dominating awareness and helps highlight a new odour.
Smell, taste and trigeminal sensation
CN I detects volatile molecules and provides much of food’s aroma and flavour complexity.
Taste receptors detect sweet, salty, sour, bitter and umami through cranial nerves VII, IX and X.
Trigeminal endings detect burning, cooling, stinging and irritation from substances such as menthol, chilli or ammonia.
Flavour is a combined perception involving retronasal smell, taste, trigeminal sensation, texture and temperature. Many patients describe reduced flavour as “loss of taste,” so each sensory component should be assessed separately.
Functions and protective value
- Recognises food and contributes to appetite, enjoyment and nutrition.
- Warns of smoke, gas, chemicals, decay and spoiled food.
- Influences salivation, gastric responses and food selection.
- Supports emotional behaviour, social cues and autobiographical memory.
- Contributes to quality of life and personal safety.
People with major smell loss should use working smoke and gas alarms, label stored food, check expiry dates and seek advice if poor appetite or unintended weight loss develops.
Clinical assessment of smell
Begin with history and a complete ENT and cranial-nerve examination. Ask whether the change was sudden or gradual, unilateral or bilateral, complete or partial, and whether odours are absent, reduced or distorted.
History points
- Nasal obstruction, discharge, allergy, sinus symptoms or polyps.
- Recent viral illness, head injury or nasal/skull-base surgery.
- Smoking, chemical exposure and current medicines.
- Neurological symptoms, cognitive change, tremor or seizures.
- Effect on appetite, body weight, safety and emotional wellbeing.
Bedside testing
- Confirm that each nostril is patent.
- Test one nostril at a time with the other gently occluded.
- Use familiar, non-irritant odours such as coffee, vanilla or soap.
- Ask the patient first to detect and then identify the odour.
- Use different items and avoid visual clues.
- Do not use ammonia as a pure olfactory test because it strongly stimulates trigeminal nerve endings.
Validated threshold, discrimination and identification tests give more reliable quantification. Nasal endoscopy, imaging, neurological assessment or other ENT investigations are selected according to suspected cause.
Terminology and smell disorders
| Term | Meaning | Example |
|---|---|---|
| Anosmia | Complete loss of smell. | May follow severe viral injury, cribriform trauma or congenital absence. |
| Hyposmia | Reduced smell sensitivity. | Common with ageing, congestion or chronic sinonasal disease. |
| Hyperosmia | Unusually increased sensitivity. | May occur in selected physiological or neurological states. |
| Parosmia | A real odour is perceived in a distorted way. | Food may smell burnt, rotten or chemically altered. |
| Phantosmia | Odour perception without an external stimulus. | May occur after infection or with selected neurological disorders. |
Conductive and sensorineural causes
- Conductive loss: odorants cannot reach the epithelium because of mucosal swelling, rhinitis, sinusitis, polyps, structural narrowing or a mass.
- Sensorineural/central loss: receptor neurons, CN I, olfactory bulb, tract or brain networks are damaged by infection, head trauma, toxins, surgery, ageing, neurodegenerative disease or other neurological conditions.
Unilateral progressive obstruction, bleeding, severe headache, neurological deficit, clear rhinorrhoea after trauma or a new persistent smell disturbance without an obvious cause requires timely specialist assessment.
Clinical scenario
A 34-year-old patient reports that food has “no taste” after a viral upper-respiratory illness. Sweet, salty and sour solutions are recognised, but coffee cannot be detected or identified through either nostril. Nasal examination shows no major obstruction.
Interpretation: preserved basic taste with impaired odour detection indicates olfactory dysfunction rather than primary gustatory loss. Document the onset and associated symptoms, assess the nose and cranial nerves, perform validated smell testing when available and investigate or refer according to duration, severity and red flags.
Key examination points
- Olfactory sensory neurons are bipolar primary receptor cells in the superior nasal cavity.
- Odorants must reach the epithelium, dissolve in mucus and activate receptor proteins.
- The main transduction pathway uses Golf, adenylyl cyclase, cyclic AMP and cation channels.
- CN I fibres pass through the cribriform plate and synapse in olfactory-bulb glomeruli.
- Mitral and tufted cells carry signals through the olfactory tract.
- Combinatorial receptor patterns allow discrimination of many odours.
- Olfactory links to limbic structures explain strong associations with emotion and memory.
- Retronasal olfaction supplies much of food flavour.
- Test each nostril separately with familiar, non-irritant odours; ammonia mainly tests trigeminal sensation.
References and further reading
- NCBI Bookshelf: Physiology, Olfactory.
- NCBI Bookshelf: The Transduction of Olfactory Signals.
- NCBI Bookshelf: The Organization of the Olfactory System.
- National Institute on Deafness and Other Communication Disorders: Smell Disorders.
- OpenStax Anatomy and Physiology: Sensory Perception.
For education only. Apply clinical findings together with current Uganda Clinical Guidelines, local protocols and specialist advice.
