Olfaction: Mechanism and Pathology

Olfaction, the sense of smell, begins in a small patch of specialized neuroepithelium high in the nasal cavity. Odorant molecules dissolve in the mucus there and bind to receptors on the cilia of olfactory sensory neurons, which convert that chemical event into nerve signals carried directly to the brain. This entry describes how smell is detected and transmitted, and the main ways that smell can be lost, including obstruction of airflow to the smell region and damage to the sensory pathway itself.

Definition

Olfaction is the sense of smell, by which odorant molecules are detected by receptor neurons in the olfactory neuroepithelium and transduced into neural signals relayed through the olfactory bulb to the brain; its loss or distortion constitutes olfactory dysfunction.

Scope

The topic covers the olfactory neuroepithelium and its receptor neurons, the molecular basis of odorant detection, the pathway from nose to olfactory bulb and brain, and the principal categories of olfactory dysfunction (conductive and sensorineural), including post-viral loss such as that associated with COVID-19. It is a reference physiology and pathophysiology entry, not a diagnostic or treatment protocol.

Core questions

• Where in the nose is the sense of smell located?
• How do odorant molecules trigger a nerve signal?
• How does that signal travel from the nose to the brain?
• What are the main mechanisms by which smell is lost or distorted?

Key concepts

• Olfactory neuroepithelium and olfactory cleft
• Olfactory sensory neurons
• Odorant receptors
• Sustentacular (supporting) cells
• Olfactory bulb and central pathway
• Conductive (obstructive) olfactory loss
• Sensorineural olfactory loss
• Anosmia, hyposmia, and parosmia

Key theories

Odorant receptor gene family

The finding that a large multigene family encodes the receptors for odorants provided the molecular basis for odour recognition and explained how the system can discriminate a vast range of smells.

Mechanisms

Olfactory sensory neurons sit in a specialized neuroepithelium high in the nasal vault, each extending cilia into the overlying mucus. Odorant molecules carried in inspired air dissolve in this mucus and bind odorant receptors on the cilia; the receptors belong to a large multigene family, identified by Buck and Axel, with each neuron expressing essentially one receptor type. Binding initiates a signalling cascade that depolarizes the neuron, and the axons project through the cribriform plate to the olfactory bulb, where signals are organized and relayed to higher brain regions for perception. Smell can fail in two broad ways: conductive loss, when airflow or odorants cannot reach the olfactory cleft (for example because of obstruction or inflammation), and sensorineural loss, when the neuroepithelium or central pathway is damaged. Post-viral olfactory loss, prominent with COVID-19, has been linked to infection and disruption of the supporting (sustentacular) cells of the olfactory epithelium rather than direct destruction of the sensory neurons alone.

Clinical relevance

Understanding olfactory anatomy and transduction explains why smell can be lost either by blocking access to the olfactory cleft or by injuring the sensory pathway, and it frames common presentations such as post-viral smell loss. This entry describes mechanisms and categories of dysfunction for educational purposes; it does not provide diagnostic criteria or treatment recommendations, which require individual clinical evaluation.

Epidemiology

Olfactory dysfunction is common and increases with age, and post-viral causes are an important category; the COVID-19 pandemic brought a marked rise in acute smell loss, drawing wide attention to olfactory pathophysiology.

Evidence & guidelines

The molecular biology of olfaction rests on the identification of the odorant receptor gene family, and clinical aspects of smell and its disorders are synthesized in the International Consensus Statement on Allergy and Rhinology: Olfaction; mechanistic work on COVID-19 anosmia has clarified how the supporting cells of the olfactory epithelium are involved.

History

The molecular era of olfaction began in 1991 when Buck and Axel identified the large family of odorant-receptor genes, work recognized with the 2004 Nobel Prize in Physiology or Medicine. Clinical olfactology was later consolidated through international consensus, and the COVID-19 pandemic intensified research into the cellular basis of acquired smell loss.

Key figures

• Linda Buck
• Richard Axel

Seminal works

• buck-axel-1991
• patel-2022-icar-olfaction
• brann-2020

Frequently asked questions

Where does the sense of smell actually happen in the nose?

In the olfactory neuroepithelium, a small specialized region high in the nasal cavity (the olfactory cleft), where receptor neurons detect odorants and send signals to the olfactory bulb of the brain.

Why does a viral infection like COVID-19 cause loss of smell?

Evidence indicates the virus chiefly affects the supporting (sustentacular) cells of the olfactory epithelium rather than directly destroying all the sensory neurons, disrupting the environment the neurons need and so impairing smell; this mechanism helps explain why smell often recovers.