The Olfactory Pathway
Sensations perceived by the body are organized into two major groups: general sensations such as touch, pressure, pain, and temperature, and special sensations such as vision, hearing, taste, smell, and the sense of body position and movement. The olfactory nerve is the first of the 12 cranial nerves and one of the few cranial nerves that carries special sensory information only. In this case, the olfactory nerve is responsible for our sense of smell.
The odor information originates in the epithelium of the nasal cavity and is transported to the brain via components of the olfactory nerve (cranial nerve 1 - CNI) and the olfactory pathway. A decreased sense of smell has been associated with Parkinson’s disease and thus, can be an important clinical marker in this and other states of disease or injury.
To understand the olfactory nerve and its clinical implications, this article will trace the olfactory nerve from its receptor cells, located in the nasal epithelium, to the olfactory cortex and beyond. It will highlight some of the unique characteristics of certain cells within the olfactory pathway, and the connection of the pathway to memory (and behavior ) related brain regions.
|Function||Special sense of smell|
|Olfactory cells||Olfactory receptor cells (sense odor and contain cilia), supporting cells, basal (stem) cells (replacing old and damaged olfactory receptor cells).|
|Olfactory nerve||CN I formed out of a collection of olfactory receptor cell axons, which pass through the cribriform plate and into the roof of the nasal cavity.|
|Olfactory bulb||It is the relay station of the olfactory pathway and contains olfactory glomeruli.|
|Olfactory tract||It is made up of the axons of mitral relay neurons.|
|Olfactory striae||They are the medial and lateral divisions of the olfactory tract.|
|Olfactory cortex||Piriform cortex, amygdala, entorhinal cortex|
|Output destination||Orbitofrontal cortex,|
Olfactory Nerve Pathway
It is important to note that the olfactory nerve is only one component of the overall pathway and is, in fact, made up of multiple nerve fibers/rootlets coming from the receptors cells. The pathway can be summarized as follows:
- olfactory receptor cells
- olfactory nerves
- olfactory bulb
- olfactory tract
- olfactory striae
- olfactory cortex
- output targets of the olfactory cortex
Olfactory Receptor Cells
These cells are located in the olfactory epithelium, a mucosal membrane that lines the roof and sides of the nasal cavity. In humans, the olfactory epithelium is small; approximately 5 cm² in area. There are three cell types contained within the epithelium: the olfactory receptor cells, supporting cells, and basal (stem) cells.
The olfactory receptor cells are bipolar, meaning that they have two projections from their cell body. One projection, the dendrite, extends to the surface of the olfactory epithelium. This dendrite expands at the epithelial surface to become knob-like. Located on the dendrite’s surface are 10-20 non motile cilia that extend into the fluid layer covering the epithelium in the nose. The cilia contain receptors for odor molecules that pass into the nasal cavity and are captured in the fluid covering the olfactory epithelium. The other projection from the receptor cell body is an unmyelinated axon; these will be described in the next step of the pathway.
Of note, other cell types present in the epithelium are the basal stem cells. Typically, an olfactory receptor cell lifespan is 30-60 days. The basal stem cells differentiate into, and replace, damaged receptor cells. This means that unlike receptive cells associated with other special senses (vision and hearing for example), cells associated with receiving olfactory information can regenerate throughout life. However, across a lifespan, not all receptors are replaced, meaning that the sense of smell can diminish with age.
Each receptor cell has an axon extending from its basal surface. The basal surface of olfactory receptor cells is located directly inferior to the cribriform plate of the ethmoid bone which makes up the bony roof of the nasal cavity. As the axons project from the cell body, they combine with other receptor cell axons, making up bundles of nerve fibers/rootlets. All of these axonal bundles can collectively be thought of as the olfactory nerve (CNI). These bundles of nerve fibers, surrounded by dura and arachnoid mater, then move superiorly by passing through the foramina (holes) in the cribriform plate of the ethmoid bone.
The axons projecting from the olfactory receptor cells via the olfactory nerve terminate within the olfactory bulb. The olfactory bulb is the main relay station within the olfactory pathway. Information from the receptor cells is passed to cells whose projections make up the subsequent olfactory tract. Each olfactory bulb (right and left) lies lateral to the crista galli and superior to the cribriform plate of the ethmoid bone, inside the cranial cavity. Therefore, it lies on the underside of medial aspect of the frontal lobe. Within the olfactory bulb are bundles of nerve fibers known as glomeruli; where incoming receptor cell axons make connections with the dendrites of mitral relay neurons.
This bundle of nerve fibers is made up of the axons of mitral relay neurons bound for the regions of the brain associated with the olfactory cortex. The tract passes posteriorly on the underside of the medial frontal lobe in a sulcus known as the olfactory groove.
Posterior and anterior to the optic chiasm, the olfactory tract on both sides divides into medial and lateral olfactory striae. The medial stria projects to the anterior commissure, and subsequently, to contralateral olfactory structures. The lateral stria continues on to structures associated with the olfactory cortex.
This cortex is not a single structure, rather, it is defined as the combined areas of the cerebral cortex (generally within the temporal lobe) that receive input directly from the olfactory bulb. These regions include the:
- Piriform cortex: which is located below the lateral olfactory stria.
- Amygdala: which is located anterior to the temporal/inferior horn of the lateral ventricle, and is associated with the emotion of fear.
- Entorhinal cortex: which is the anterior part of the parahippocampal gyrus, and is involved in the formation of memory.
Olfactory Cortex Output Structures
From the olfactory cortex, information about smell is sent to the orbitofrontal cortex via the dorsal medial nucleus of the thalamus. The orbitofrontal cortex is a portion of the prefrontal cortex that is located on the underside of the frontal lobe and situated over the eye orbit. Lesions of this cortical region can result in an inability to distinguish different odors. Odor information is also sent to portions of the hypothalamus and brainstem that trigger autonomic responses involved in appetite, salivation, and gastric contraction.
A complete lack of smell (anosmia), or distortions in smell (dysosmia), can be indicative of a number of different clinically important injuries and diseases.
A change in the acuity of smell perception or a complete lack of smell perception can be a symptom associated with a number of neurological degenerative diseases such as:
- Alzheimer’s disease
- Huntington’s disease
- Multiple sclerosis
- Pick’s disease (a form of dementia)
- Parkinson’s disease - anosmia in Parkinson’s patients may precede the motor symptoms by years and may be a useful screening test for the early detection of the disease.
Anosmia may also arise due to other forms of brain injury:
- Brain tumors or aneurysms that press on a part of the olfactory pathway.
- Head trauma with a fracture of the superior orbit, or anterior cranial fossa.
Dysosmias can fall under different categories: a distortion in the quality of the perception of an odor (parosmia/troposmia/cacosmia) or, the perception of an odor when no odor is actually present (phantosmia/olfactory hallucinations). Damage to olfactory nerve fibers can occur as a complication of upper respiratory tract infections. A decrease in the number of nerve fibers from these infections mean that there are not enough different fibers to accurately differentiate odors resulting in parosmia. Phantosmia can occur as the initial event, or aura, associated with temporal lobe epilepsy and may indicate a partial seizure that then spreads further into temporal lobe structures.
Changes in the level of odor perception or in the quality of odor perception, in the absence of any sinus or nasal cavity issues, should be of concern clinically and tested thoroughly. Initially, the sense of smell can easily be tested by using well known odors (such as coffee, menthol, peppermint, etc).