How Does the Sense of Smell Work?

Odor molecules enter the nasal passage and sweep past the olfactory epithelium, where olfactory neurons reside. The odor signal is transmitted through the olfactory nerves into the olfactory bulb and is sent to the brain regions that process smell, including the amygdala, the hippocampus, and the orbitofrontal cortex.

Olfactory neurons in the olfactory epithelium present cilia into the nasal passage. Odor molecules bind to olfactory receptors on the cilia and trigger an action potential inside the olfactory neuron. This signal is then transmitted to synapses of tufted cells in the glomeruli in the olfactory bulb.

Healthy olfactory neurons have numerous olfactory receptors coupled to G proteins.

Upon binding an odor molecule, they activate adenylate cyclase III (ACIII), which generates cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP).

cAMP activates cAMP-gated calcium channels (CNG), leading to calcium influx, which in turn triggers an action potential.

Calcium influx also shuts the cAMP signal down by triggering phosphodiesterase (PDE) activity, leading to cAMP degradation to adenosine monophosphate (AMP).