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Olfactory Nerve

You might have come across an uncommon but very special case in your social circle. Some of your colleagues might have told you that he/she dislikes the smell of beautiful roses or jasmine flowers or the romantic fragrance of waterlily. This might be surprising to you, but these people exist. In a disease of the olfactory pathway, the sense of smell may get perverted. Clinically, this is called parosmia (a perverted sense of smell). These people, when they smell a rose, may have a sense of rotten eggs smell or a smell of a heap of dung. This condition may occur following some viral infections or other causes. The olfactory nerve is the main culprit. This article will deal with the Olfactory Nerve, its origin, course, classification, and functional component(s), etc. We shall also discuss the olfactory stimuli, receptors for olfaction, different olfactory pathways, and their functions. Lastly, we shall see some diseases related to olfactory nerve and their management.

Illustration showing the location and structure of the olfactory nerve
Illustration showing the location and structure of the olfactory nerve

Olfactory Nerve

There are twelve pairs of cranial nerves that supply sensory and motor innervation to the area of the head and neck. These nerves are numbered CN I to CN XII. The olfactory nerve is the first cranial nerve (CN I) that carries a very special visceral sensation, the sense of smell, to the central nervous system. It receives odorous information from the environment and sends it to the olfactory areas of the brain cortex. Along with a sense of taste, olfactory sensation helps in choosing food. A food item with an unpleasant scent will be refused but may enhance your appetite if it possesses a good smell.

Read more about the Peripheral Nervous System 

Origin and Course of Olfactory Nerve

The olfactory Nerve originates from the mucous membrane of the superior surface of the nasal cavity or roof of the nasal cavity. This specialized area is known as the olfactory epithelium. It has two types of cells. 1) Olfactory nerve cells, which contain olfactory receptors and receive olfactory information, and 2) Sustentacular cells, which provide nourishment and support to the neuronal cells. In case of olfactory cell degeneration, these sustentacular may give rise to new cells. Axons of these cells ascend upwards, travel through the numerous small holes in the cribriform plate of the ethmoid bone, which forms the bony framework of the roof of the nasal cavity and enter into the anterior cranial fossa of the skull. On the cranial surface of the cribriform plate, there is a collection of cell bodies of mitral cells, known as the olfactory bulb. Neurons coming from the olfactory epithelium synapse with these mitral cells, forming small structures known as glomeruli present in the olfactory bulb. Second-order neurons from the olfactory bulb travel to the inferior surface of the brain and reach the olfactory cortex. The olfactory area is divided into two parts; 1) the Medial olfactory area and 2) the Lateral olfactory area, each having specific functions.

Classification and Functional Components

The olfactory nerve (CN I) is a pure sensory nerve. It does not have any motor supply. It contains only special visceral afferent fibers which carry special visceral sensations to the central nervous system. 

Sense of smell is the only sense that does not relay in the thalamus, the main sensory collection center of the brain. The olfactory nerve just bypasses the thalamus and reaches the olfactory area. All the other sensations, either general (i.e., touch, pain, pressure, warmth, cold, etc.) or special (i.e., vision, hearing, and taste, etc.), the relay in the thalamus before going to the specialized areas in the cortex.

Olfactory Stimuli

Stimuli for olfaction are odorants present in the air. Odorants are substances that bind with the olfactory receptors and cause sensations of smell. These odorants are small volatile molecules that have both water and lipid solubility. Water solubility helps them in crossing the layer of mucous produced by the nasal glands. Lipid soluble property allows them to cross the lipid constituent of the olfactory cilium (discussed later). 

Olfactory Receptors

Olfactory cells are the bipolar neurons, also known as olfactory neurons. These are the same neurons that form the olfactory nerve. The mucosal end of these neurons forms knob-like structures in the olfactory epithelium. Up to 25 hair-like structures emerge from the knob and project into the nasal cavity. These hair-like projections are known as olfactory cilia. These cilia have olfactory receptors on their membrane. The receptors are actually G-protein coupled receptors.

When an odorant molecule binds with the odorant receptor, the alpha component of the attached G-protein dissociates from the beta & gamma components and binds to another trans-membrane enzyme known as adenylyl cyclase. Adenylyl cyclase converts ATP molecules into cyclic AMP (cAMP). This cAMP, in turn, binds with ligand-gated Na channels. Activated Na channels open up, and sodium influx occurs. This sodium influx generates an action potential which is transmitted via the olfactory nerve to the brain. At each step of this cascade, one enzyme activates many enzymes of the next step. This results in strong amplification of even the weakest odorant. That is the basis of the very small threshold for the smell. For example, the substance “methylmercaptane” can be smelled even if there is only one-trillionth of a gram of this substance is present in a millimeter of air. We know that natural gas is odorless and colorless. Its leakage can be very dangerous. That’s why a small amount of methyl mercaptan is added to the natural gas to detect even a small leakage from the pipeline. 

Olfactory receptors are rapidly adapting receptors with about more than 50% adaption in the first few seconds. This adaptation occurs due to both neural and psychological mechanisms. The neuronal mechanism involves inhibition by the granule cells present in the olfactory bulb of the CN I. 

Like the three primary colors for vision or the five primary sensations of taste, there have been many attempts to check for the primary smell sensations. Seven primary sensations for smell have been identified:

  • Floral
  • Musky
  • Camphoraceous
  • Ethereal
  • Pepperminty
  • Pungent
  • Putrid

This list does not include the total primary sensations. It is estimated that more than 100 primary sensations are there for the smell. More astonishingly, some studies suggest that there may be at least 1000 different smell receptors present in the olfactory epithelium.

Olfactory Pathways

The olfactory tract, after entering the brain, is divided into two main pathways; 1) the Primitive pathway and 2) the Less old pathway. Both these pathways bypass the thalamus and directly enter the brain cortex.

Primitive Pathway Leading to the Medial Olfactory Area

The medial olfactory area is the primitive area consisting of some portions of the brain’s limbic system as well as some midline nuclei that feed the hypothalamus. This pathway is called primitive or very old pathway according to the evolutional development of organisms. This pathway is concerned only with some basic reflexes associated with smell, i.e., licking, salivation, or some emotional responses. 

Less Old Pathway Leading to the Lateral Olfactory Area

The lateral olfactory area consists of some cortical portions of amygdaloid nuclei as well as piriform and prepiriform cortices. This pathway is linked with some partially learned responses related to liking or disliking a food etc. This helps an organism to develop a specific behavior for some foods that can cause nausea etc. These responses are learned but automatic and not involved in conscious smell perception. Removal of lateral olfactory areas does not affect the basic responses exhibited by the primitive pathway.

The Newer Pathway

We pointed out earlier that the olfactory sense bypasses the thalamus, the main sensory relay station of the brain. However, some studies have pointed out a newer pathway that is present in some higher animals according to evolutionary history. This pathway does not bypass the thalamus like the older ones. This pathway seems to be involved in the conscious analysis of odor.

Advantage of Olfactory Sense

Olfaction has played a very important role in the evolutionary history of organisms, especially animals. Animals used this sense for food search. The smell of food is an important parameter for liking or disliking any food item. Cheese has been one of the most popular ingredients in food items for a very long. But some people dislike the smell of cheese and so dislike every fast-food item that contains cheese. The smell of the food also depends upon its freshness and readiness. If something has been spoiled, it smells putrid, so none of us would like it. A putrid eatable may cause severe food poisoning. In this way, a sense of olfaction prevents the intake of any spoiled or rotten food item. Household flies and ants use the same olfactory sense to search for food. This is the reason that ants can reach the most hidden food item in your kitchen!

There are certain gases that have a pungent smell, like ammonia and chlorine, that are very toxic to the human body. Sensing their smell in the environment helps us to take precautionary measures to prevent any hazardous effects of these gases. 

In animals, olfaction plays a very significant role in choosing a partner. Some females release pheromones that attract their male counterparts toward them and vice versa. This pheromone secretion also indicates the breeding season in some animal species. 

Sense of olfaction has a very deep connection to our mood and behavior. A good fragrance can make your day. This also has an emotional touch. Some fragrances have been attached to our past memories, causing nostalgia. 

Diseases Related to CN I

There are many diseases that affect the nervous system. Some of them are systemic, which affects the nervous system as a whole, and some are localized to particular nerves. We will limit our discussion to olfactory nerve and olfactory pathways.

Anosmia or Hyposmia

Anosmia is the complete loss of olfaction. These persons cannot smell anything. In hyposmia, there is a partial loss of olfactory sensation rather than a complete loss. Anosmia may be congenital. In congenital anosmia, there may be the absence of olfactory epithelium, malformation of the olfactory nerve, or developmental issues in the olfactory area of the brain. The exact cause of this congenital anomaly is not known, however, genetic as well as developmental abnormalities may result in this condition. Congenital anosmia is a very rare condition. Currently, we can do nothing in this case. 

Acquired anosmia can occur due to damage to the olfactory nerve caused by direct trauma, nasal polyps, tumors pressing the nerve, or infectious diseases that can damage the nerves. Once the olfactory nerve is seriously damaged or sheared due to any of these stresses, the loss is irreversible, resulting in permanent anosmia. Transient anosmia may occur in flu, rhinitis or sinusitis, common cold, and Covid-19. This condition can be treated by treating the underlying disease. In case of nasal polyps etc., surgery may be performed to cure this disease. 

Hyposmia is the partial loss of olfaction. Causes of hyposmia include nasal polyps, viral infections, especially the very well-known coronavirus infection, Alzheimer’s diseases that diminish brain abilities, cancers, brain surgery, chemical exposure, multiple sclerosis, etc. 

Parosmia or Dysosmia

Parosmia is the perversion/distortion of smell sensation. In this condition, the affected person missenses an odor, i.e., the fruity smell of a fresh apple may appear as rotten or putrid bread. The person may feel a persistent foul smell everywhere. This can cause nausea and irritation. Whenever such a person tries to eat something, the apparent foul smell causes the person to refuse to eat, which can lead to malnutrition. 

Parosmia often follows an infection, especially a viral infection. The well-known Corona Virus infection is a good example. Other causes may include tumors, traumatic brain injury, exposure to toxins or chemicals, and neurologic conditions. In all the conditions, there is damage to olfactory cells in the olfactory epithelium, olfactory nerve, or olfactory areas of the brain cortex. 

Phantosmia

Phantosmia is a rare condition in which a person feels smells that do not even exist. There is no odorant in the environment, yet the affected person is feeling a scent. This resembles conditions like visual or auditory hallucinations. This may result due to CNS disturbance, depression, anxiety, etc.

Treatment of Phantosmia involves psychological therapy like counseling. Once the CNS activity returns to normal, Phantosmia may disappear. 

Odor Blindness

Odor blindness is a special case. It is characterized by the absence of one or more types of olfactory receptors resulting in a loss of capability to sense that particular smell. when there are no receptors, the corresponding odorants cannot stimulate the olfactory nerve, even if present in very large amounts in the environment. This is actually the Anosmia of a particular smell. 

Summary

The olfactory nerve is the first cranial nerve. It is a sensory nerve with special visceral afferents as functional components. It arises from the bipolar neurons of the olfactory epithelium located at the superior aspect of the nasal cavity. 

From the olfactory epithelium, several small nerve fibers enter the skull through the cribriform plate of the ethmoid bone and form an olfactory bulb. The synapse between bipolar olfactory neurons and mitral cells of the bulb takes place. 

From the olfactory bulb, the olfactory tract reaches the olfactory area of the brain. The olfactory area is divided into two parts; 1) the medial olfactory area and 2) the Lateral olfactory area. Odorants bind with the receptors present on the hair-like projections of olfactory neurons. 

These G-protein coupled receptors, in turn, activates the adenylyl cyclase enzyme and convert ATP to cAMP. Increased cAMP concentration causes the Na channels to open up, and action potential develops, which is carried to the CNS via the olfactory nerve. 

There are more than 100 primary olfactory sensations that have been identified. Out of 100, seven important primary olfactory sensations are floral, musky, ethereal, camphoraceous, pepper minty, pungent, and putrid. An estimate of up to 1000 different olfactory receptors has been made. 

Olfactory sensations reach the brain via the primitive olfactory pathway connected to the medial olfactory area (involved in basic olfactory responses, i.e., licking, etc.) and the less old pathway connected to the lateral olfactory area (involved in partially learned but automatic responses, i.e., liking & disliking of food). A third pathway has also been identified, which functions in conscious perception and analysis of odor. Sense of olfaction is important in choosing food and prevention of damage due to gases like chlorine etc. 

Diseases of the olfactory system include anosmia (loss of olfaction), hyposmia (decreased olfaction), parosmia (distorted olfaction), Phantosmia (olfactory hallucinations), and odor blindness. 

References

Mcgraw Hill’s Anatomy and Physiology Revealed

Vilensky, Joel; Robertson, Wendy; Suarez-Quian, Carlos (2015). The Clinical Anatomy of the Cranial Nerves: The Nerves of “On Old Olympus Towering Top”. Ames, Iowa: Wiley-Blackwell. ISBN 978-1118492017.

Saladin, Kenneth. “The Cranial Nerves.” Anatomy and Physiology: The Unity of Form and Function. 6th ed. New York City: Mcgraw-Hill, 2012. 548.Image source: Ophthalmic Nerve