The initial events in olfaction take place in an olfactory neuroepithelium situated in the posterior nasal cavity. The olfactory receptor neurons (ORNs) direct their unbranched axons to the olfactory bulb (OB), passing through the cribriform plate. Each neuron has a single axon. Within the OB, the ORN axons form contact with secondary neurons (mitral and other cells) in spherical neuropils, called glomeruli. ORN have a few dozen hairlike cellular structures, called olfactory cilia. Cilia harbor the sensory apparatus (olfactory receptor (OR) proteins and other components) that converts and amplifies the physical-chemical signal of the odorant molecule into electric current. Wiring of the olfactory system allows discrimination between a large number of odorants: ORNs expressing a particular OR send their axons to the same glomerulus. ORs have been found to belong to the large superfamily of G-protein coupled receptors. It is important that only one type out of the hundreds of possible receptors is expressed in each ORN (one neuron-one receptor rule). Therefore, each glomerulus carries an amplified signal of many olfactory neurons that share information of the same OR type. Olfaction begins with sniffing that transports odorant molecules into the nose and delivers them to the mucus layer covering the olfactory epithelium. The binding of the odorant by a receptor protein initiates an intracellular cascade of signal transduction events, including the G-protein-dependent production of second messenger molecules, leading to the opening of ion channels and passing of ion currents. This process triggers an action potential in the ORN axon that projects directly to OB and communicates with the synaptic connection with mitral and other cells in the glomerulus. From the olfactory bulb, the information is further sent to the cortex for recognition of the signal. Finally, the odorant is cleared from mucus, and the process begins again.

A bigger picture. The initial events in olfaction take place in an olfactory neuroepithelium situated in the posterior nasal cavity. Olfaction begins with sniffing, that transports odorant molecules into the nose and delivers them to the mucus layer covering the olfactory epithelium. The binding of the odorant by a receptor protein initiates an intracellular cascade of signal transduction events, including the G-protein-dependent production of second messenger molecules, leading to opening of ion channels and passing of ion currents. This process triggers an action potential in the olfactory receptor neurons (ORNs) that projects directly to the olfactory bulb (OB). The signal is then transmitted to the anterior olfactory nucleus, piriform cortex, periamygdaloid cortex, and entorhinal cortex via olfactory stria. The signal at piriform cortex and periamygdaloid cortex is then sent to the thalamus and frontal cortex, where it is recognized and interpreted. The signal received at the entorhinal cortex projects to the hippocampus, where recognition memory of odors is processed. The anterior olfactory nucleus is involved in the processing of olfactory features and construction of representations (gestalts) for odorants. The correlations between olfactory gestalts are processed by the piriform cortex in association with frontal, entorhinal, and periamygdaloid areas. The periamygdaloid area is involved in processing the emotional information of the olfactory stimuli and memory encoding, whereas the entorhinal cortex collects and distributes information about olfactory memory and serves as a top-down modulator of olfactory cortical function. The medial and orbital parts of the frontal cortex are involved in cognitive integration of all sensory stimuli in relation to prior experiences. The thalamus’ role in olfaction is still controversial, whereas its involvement in odor thresholding and patterns of sniffing has been verified, at least in humans.