Smell

Olfactory sensory neurons

The neurons are involved with transmitting olfactory information centrally. They are bipolar cells with an apical ciliated dendrite and an unmyelinated axon extending from the basal surface. Each dendritic knob has an average of 10 to 30 cilia extending into the mucus lining covering the olfactory epithelium. The axons of the sensory neurons, compose fiber bundles, called fila olfactoria (or olfactory nerves), traverse the lamina propria and pass through the cribriform plate of the ethmoid bone to synapse in the olfactory bulb.

Supporting cells

Those are are long, columnar cells whose function is to provide metabolic and physical support and insulation to the sensory neurons, acting similarly to glial cells. They express various cytochrome P450 enzymes and other biotransformation enzymes, aiding in the metabolization of foreign substances, detoxification of compounds encountered by the OE, and phagocytosis of dead olfactory neurons and odorants.

Basal cells

Basal cells are located adjacent to the basal lamina in the olfactory epithelium basal region. They can differentiate to support lifelong renewal of the epithelium lost due to normal turnover or injury. Basal cells are divided into globose cells, serving as both reserve and active progenitors, and horizontal cells, activated in response to injury.

Olfactory bulbs

The olfactory bulbs are located in the ventral surface of the frontal lobe serving as relay stations for signals transmitted from the olfactory epithelium to the primary olfactory cortex. They contain several types of neurons including mitral cells, tufted cells, granule cells, and periglomerular cells. Axons from sensor neurons terminate in the olfactory bulb, where they converge with the dendrites of mitral and tufted cells in structures called glomeruli, forming discrete synaptic units. Periglomerular cells and granule cells are inhibitory GABAergic interneurons that refine olfactory signals, enhancing odor discrimination. Granule cells located in the deeper layers of the olfactory bulb, lack axons and communicate through dendrodendritic synapses with mitral and tufted cells. Periglomerular cells are found in the outer layer of the olfactory bulb, surrounding the glomeruli.

Olfactory receptors

Olfaction starts when odorants interact with olfactory receptors in the nasal mucosa. When odorants enter the nasal cavity, they activate receptors located in the cilia of olfactory sensory neurons, initiating odorant signal transduction. These receptors are also present in the axonal processes of olfactory sensory neurons, aiding in axonal targeting to specific glomeruli within the olfactory bulb.

Olfactory receptoes belong to the G protein-coupled receptor (GPCR) superfamily and exhibit high diversity in their amino acid sequences, consequently allowing them to detect a wide range of odorants. The number of receptors' genes varies among species; for example, mice possess around 1,000 OR genes, while humans have about 400.

When odorants bind to receptors, they activate the associated heterotrimeric G-protein, known as Golf. This activation triggers a chain of events; first, the Golf protein exchanges GDP for GTP, which then activates an enzyme called adenylyl cyclase III (ACIII). This leads to an increase in intracellular cAMP, acting as a signaling molecule. Elevated cAMP levels open cyclic nucleotide-gated ion channels, permitting an influx of Na⁺ and Ca²⁺ ions, which ultimately depolarizes the olfactory sensory neuron, generating an action potential.

From the olfactory nerve to the brain

The olfactory nerve (cranial nerve I) is crucial for the perception of smell. It begins in the nasal cavity and extends to the brain. Inspired air is directed toward the olfactory epithelium, where odorants activate olfactory receptors and stimulate the olfactory sensory neurons, as described above. The axons of these neurons pass through the cribriform plate of the ethmoid bone to reach the olfactory bulb, crossing the subarachnoid space. There, they synapse with mitral and tufted cells in the glomeruli.

The axonal projections from mitral and tufted cells form bundles that exit the olfactory bulb, forming the olfactory tract. The olfactory tract runs posteriorly along the olfactory sulcus, ending at the olfactory trigone, a triangular area superior to the anterior clinoid process and just rostral to the anterior perforated substance. Here, the fibers diverge into two pathways:

• The lateral olfactory stria which is responsible for most olfactory signal transmission. It carries efferent projections towards the limen insula (the most anteroinferior part of the insular cortical surface), bending medially into the temporal lobe, near the uncus. From there it reaches the primary olfactory cortex, which includes areas like the piriform cortex, amygdala, parahippocampal gyrus. These regions are also responsible for memory, emotion, and conscious smell perception.

• The medial olfactory stria which responsible for autonomic responses associated with olfaction, e.g., increased salivation and gastric peristalsis triggered by smells. It projects to the ipsilateral anterior olfactory nucleus and, via the anterior commissure, to the contralateral olfactory bulb, ending in septal nuclei around the para-terminal gyrus. From here, two secondary fiber bundles emerge:
  • the medullary stria pathway, which activates the superior and inferior salivatory nuclei, and
  • the olfactory-hypothalamic-tegmental bundle, which interacts with the dorsal vagal nucleus to increase peristalsis and gastric secretion.

Olfactory projections are mainly unilateral, but fiber bundles from the olfactory peduncle cross through the anterior commissure to reach the opposite olfactory bulb and cortex, enabling interhemispheric olfactory information transfer. Commissural fibers from the anterior piriform cortex also facilitate this transfer. In humans, contralateral olfactory projections generally have inhibitory effects, thus regulating the sense of smell. Feedback loops from many olfactory cortical areas, including the anterior olfactory nucleus and piriform cortex, project back to the olfactory bulb.

The sense of smell is important for the nervous system. Learn more about the anatomy of the nervous system with our beginner-friendly quizzes and labeled digrams.