The sense of smell is achieved through the activities of the olfactory system. It starts when an airborne odorant enters the nasal cavity and reaches olfactory epithelium (OE). The OE is protected by a thin layer of mucus, which also serves the purpose of dissolving more complex compounds into simpler chemical odorants. The size of the OE and the density of sensory neurons varies among species; in humans, the OE is only about 9-10 cm².

The olfactory receptors are embedded in the cilia of the olfactory sensory neurons. Each neuron expresses only one type of olfactory receptor. However, each type of olfactory receptor is broadly tuned and can bind to multiple different odorants. For example, if receptor A binds to odorants 1 and 2, receptor B may bind to odorants 2 and 3, while receptor C binds to odorants 1 and 3. Thus, the detection and identification of an odor depend on the combination of olfactory receptors that recognize the odor; this is called combinatorial diversity.

Olfactory sensory neurons are bipolar cells with a single long axon that sends olfactory information up to the olfactory bulb (OB). The OB is a part of the brain that is separated from the nasal cavity by the cribriform plate. Because of this convenient proximity between the nose and brain, the development of nasal drug applications is widely studied, especially in cases where direct access to the central nervous system is preferred.

Within the OB, axons from sensory neurons terminate in a specialized area called a glomerulus. Sensory neurons with the same olfactory receptor type send their axons to the same one or two glomeruli. As a result, there can be thousands of axons from similar sensory neurons converging within a single glomerulus. All of that sensory information is passed on to only 20-50 mitral and tufted cells per glomeruli, so there is a large convergence of information. Periglomerular and granular cells are inhibitory interneurons that mediate cross-talk between mitral/tufted cells before the olfactory information is sent to the cortex.

From the OB, the mitral/tufted cells project information to the olfactory cortex. The olfactory cortex is a complex of several cortical areas that process olfactory information. One olfactory area, the cortical amygdala, influences emotional responses to smell. The orbitofrontal cortex is involved in the identification of odors and the reward value of odors and tastes. The entorhinal cortex, another olfactory cortical area, projects to the hippocampus, which is implicated in olfactory memory.

The ability to detect and identify odors involves higher-order cortical areas. Such high-level integration may be linked to the impaired olfactory functioning observed in many neurodegenerative disorders, such as Parkinson’s and Alzheimer’s diseases. The reduced ability to smell—hyposmia—is an early symptom of both disorders.