The olfactory nerve, also known as the first cranial nerve, cranial nerve I, or simply CN I, is a cranial nerve that contains sensory nerve fibers relating to the sense of smell. The

afferent nerve fiber Afferent nerve fibers are axons (nerve fibers) of sensory neurons that carry sensory information from sensory receptors to the central nervous system. Many afferent projections ''arrive'' at a particular brain region. In the peripheral nerv ...

s of the

olfactory receptor neuron An olfactory receptor neuron (ORN), also called an olfactory sensory neuron (OSN), is a sensory neuron within the olfactory system. Structure Humans have between 10 and 20 million olfactory receptor neurons (ORNs). In vertebrates, ORNs are Bi ...

s transmit

nerve impulse An action potential (also known as a nerve impulse or "spike" when in a neuron) is a series of quick changes in voltage across a cell membrane. An action potential occurs when the membrane potential of a specific Cell (biology), cell rapidly ri ...

s about

odor An odor (American English) or odour ( Commonwealth English; see spelling differences) is a smell or a scent caused by one or more volatilized chemical compounds generally found in low concentrations that humans and many animals can perceive ...

s to the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

(

olfaction The sense of smell, or olfaction, is the special sense through which smells (or odors) are perceived. The sense of smell has many functions, including detecting desirable foods, hazards, and pheromones, and plays a role in taste. In humans, ...

). Derived from the

embryo An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sp ...

nic

nasal placode In embryology, the nasal placode (or olfactory placode) gives rise to the olfactory epithelium of the human nose, nose. Two nasal Neurogenic placode, placodes arise as thickened ectoderm from the frontonasal process. They give rise to the human n ...

, the olfactory nerve is somewhat unusual among cranial nerves because it is capable of some regeneration if damaged. The olfactory nerve is sensory in nature and originates on the

olfactory mucosa The olfactory mucosa is the Neuroepithelial cell, neuroepithelial mucosa lining the roof and upper parts of the Nasal septum, septum and lateral wall of the nasal cavity which contains Bipolar neuron, bipolar neurons of the primary receptor neur ...

in the upper part of the

nasal cavity The nasal cavity is a large, air-filled space above and behind the nose in the middle of the face. The nasal septum divides the cavity into two cavities, also known as fossae. Each cavity is the continuation of one of the two nostrils. The nas ...

. From the olfactory mucosa, the nerve (actually many small nerve fascicles) travels up through the

cribriform plate In mammalian anatomy, the cribriform plate (Latin for lit. '' sieve-shaped''), horizontal lamina or lamina cribrosa is part of the ethmoid bone. It is received into the ethmoidal notch of the frontal bone and roofs in the nasal cavities. It s ...

of the

ethmoid bone The ethmoid bone (; from ) is an unpaired bone in the skull that separates the nasal cavity from the brain. It is located at the roof of the nose, between the two orbits. The cubical (cube-shaped) bone is lightweight due to a spongy constructi ...

to reach the surface of the brain. Here the fascicles enter the

olfactory bulb The olfactory bulb (Latin: ''bulbus olfactorius'') is a neural structure of the vertebrate forebrain involved in olfaction, the sense of smell. It sends olfactory information to be further processed in the amygdala, the orbitofrontal cortex (OF ...

and synapse there; from the bulbs (one on each side) the olfactory information is transmitted into the brain via the olfactory tract. The fascicles of the olfactory nerve are not visible on a cadaver brain because they are severed upon removal.

Structure

The specialized

s of the olfactory nerve are located in the olfactory mucosa of the upper parts of the

. The olfactory nerves consist of a collection of many sensory nerve fibers that extend from the olfactory epithelium to the

, passing through the many openings of the

, a sieve-like structure of the

. The sense of smell arises from the stimulation of receptors by small molecules in inspired air of varying spatial, chemical, and electrical properties that reach the nasal epithelium in the nasal cavity during inhalation. These stimulants are transduced into electrical activity in the olfactory neurons, which then transmit these impulses to the olfactory bulb and from there they reach the olfactory areas of the brain via the olfactory tract. The olfactory nerve is the shortest of the twelve cranial nerves and, similar to the optic nerve, does not emanate from the

brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is conti ...

Function

The olfaction system works to ensure that people can successfully identify an extensive range of odorants and distinguish odors from one another. Odorants interact with the olfactory receptor neurons (ORNs) at the periphery and transmit olfactory information to the

via

axons An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see spelling differences) is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action pot ...

at the basal surface. These axons aggregate, forming the olfactory nerve. Therefore, the olfactory nerve works to transduce sensory stimuli in the form of odorants and encode them into electrical signals, which are relayed to higher-order centers through synaptic transmission.

Odor Transduction

Odorants bind to specific odorant receptor proteins contained to the outer surface of olfactory cilia within the

olfactory epithelium The olfactory epithelium is a specialized epithelium, epithelial tissue inside the nasal cavity that is involved in olfaction, smell. In humans, it measures and lies on the roof of the nasal cavity about above and behind the nostrils. The olfact ...

. Odorant binding to the cilia of an ORN evokes an electrical response, kickstarting odor transduction. An individual ORN contains several microvilli, olfactory cilia, which protrude from a knoblike structure at the apical surface involved in dendritic processes. The olfactory cilia lack the

cytoskeletal The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all Cell (biology), cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane ...

features of motile cilia and are, therefore, more similar to microvilli like that found in the lungs or gut. Olfactory cilia are

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ...

-rich protrusions supported by scaffolding proteins which help to localize odorant receptors and provide an increased cellular surface for odorant binding. Homologous to G-protein-coupled receptors (GPCRs), olfactory receptor molecules consist of seven trans-membrane,

hydrophobic In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thu ...

domains and a cytoplasmic domain with a carboxyl terminal region that interacts with G-proteins and odorants. Once an odorant is bound to an odor receptor protein, the alpha subunit of an olfactory-specific heterotrimeric G-protein, G_olf, dissociates and activates olfactory-specific adenylate cyclase, adenylyl cyclase III (ACIII). Activation of ACIII leads to an increase in cyclic AMP (cAMP), which depolarizes the neuron due to an influx of Na+ and Ca2+ by opening cyclic nucleotide-gated ion channels. The neuron is further depolarized by a Ca2+-activated Cl- current travelling from the cilia, where the depolarization first occurred, to the axon hillock of the ORN. At the axon hillock, voltage-gated Na+ channels open and generate an

action potential An action potential (also known as a nerve impulse or "spike" when in a neuron) is a series of quick changes in voltage across a cell membrane. An action potential occurs when the membrane potential of a specific Cell (biology), cell rapidly ri ...

that is transmitted to the

. After transmission, the ORN membrane is repolarized by calcium/calmodulin kinase II-mediated mechanisms that work to extrude Ca2+ and transport Na+ via an Na+/Ca2+ exchanger, diminish cAMP levels by activating phosphodiesterases, and restore heterotrimeric G_olf. ORN axons are responsible for relaying odorant information to CNS through action potentials. The ORN axons leave the olfactory epithelium and travel ipsilaterally to the olfactory bulb where the ORN axons coalesce into multiple clusters, called glomeruli, which together form the olfactory nerve. The ORN axons of each glomerulus synapse with apical dendrites of mitral cells, the primary projection neurons of the olfactory bulb, which create and send action potentials further into the CNS.

Regeneration of Olfactory Nerves

ORNs directly interact with odorants inhaled into the olfactory epithelium which can also subject the ORNs to damage through continuous exposure to harmful substances such as airborne pollutants,

microorganisms A microorganism, or microbe, is an organism of microscopic size, which may exist in its single-celled form or as a colony of cells. The possible existence of unseen microbial life was suspected from antiquity, with an early attestation in ...

, and allergens. Therefore, ORNs maintain a normal cycle of degeneration and regeneration. The olfactory epithelium consists of three main cell types: supporting cells, mature ORNs, and basal cells. Regeneration of ORNs requires the division of basal cells, neural stem cells, to produce new receptor neurons. This regeneration process makes ORNs unique when compared to other neurons.

ORN Specificity

In the nasal passages, inhaled odorant molecules interact with receptor proteins on localized neuronal cilia of ORNs. These dendritic extensions, cilia, express one type of protein receptor, although individual odorants can interact with multiple different receptor proteins. As new ORNs mature, they have decreased expression levels of multiple olfactory receptor

genes In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

, contrasting with mature ORNs firm rule of one neuron—one expressed olfactory receptor gene. Moreover, different odors activate specific ORNs in a molecular and spatial manner due to receptor specificity. Some ORNs contain receptor proteins with high affinity for some odorants, with distinct odor selectivity to a specific chemical structure, while other receptor proteins are less selective.

Clinical significance

Examination

Damage to this nerve leads to impairment or total loss of the sense of smell (

anosmia Anosmia, also known as smell blindness, is the lack of ability to detect one or more smells. Anosmia may be temporary or permanent. It differs from hyposmia, which is a decreased sensitivity to some or all smells. Anosmia can be categorized int ...

). To simply test the function of the olfactory nerve, each

nostril A nostril (or naris , : nares ) is either of the two orifices of the nose. They enable the entry and exit of air and other gasses through the nasal cavities. In birds and mammals, they contain branched bones or cartilages called turbinates ...

is tested with a pungent odor. If the odor is smelled, the olfactory nerve is likely functioning. On the other hand, the nerve is only one of several reasons that could explain if the odor is not smelled. There are olfactory testing packets in which strong odors are embedded into cards and the responses of the patient to each odor can be determined.

Lesions

Lesions to the olfactory nerve can occur because of "blunt trauma", such as coup-contrecoup damage, meningitis, and tumors of the

frontal lobe The frontal lobe is the largest of the four major lobes of the brain in mammals, and is located at the front of each cerebral hemisphere (in front of the parietal lobe and the temporal lobe). It is parted from the parietal lobe by a Sulcus (neur ...

of the brain. These injuries often lead to a reduced ability to taste and smell. Lesions of the olfactory nerve do not lead to a reduced ability to sense pain from the nasal epithelium. This is because pain from the nasal epithelium is not carried to the central nervous system by the olfactory nerve - it is carried to the central nervous system by the

trigeminal nerve In neuroanatomy, the trigeminal nerve (literal translation, lit. ''triplet'' nerve), also known as the fifth cranial nerve, cranial nerve V, or simply CN V, is a cranial nerve responsible for Sense, sensation in the face and motor functions ...

Aging and smell

A decrease in the ability to smell is a normal consequence of human

aging Ageing (or aging in American English) is the process of becoming Old age, older until death. The term refers mainly to humans, many other animals, and fungi; whereas for example, bacteria, perennial plants and some simple animals are potentiall ...

, and usually is more pronounced in men than in women. It is often unrecognized in patients except that they may note a decreased ability to taste (much of taste is actually based on reception of food odor). Some of this decrease results from repeated damage to the olfactory nerve receptors due likely to repeated upper respiratory infections. Patients with

Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...

almost always have an abnormal sense of smell when tested.

Pathway to the brain

Some

nanoparticle A nanoparticle or ultrafine particle is a particle of matter 1 to 100 nanometres (nm) in diameter. The term is sometimes used for larger particles, up to 500 nm, or fibers and tubes that are less than 100 nm in only two directions. At ...

s entering the nose are transported to the brain via olfactory nerve. This can be useful for nasal administration of medications. It can be harmful when the particles are soot or magnetite in

air pollution Air pollution is the presence of substances in the Atmosphere of Earth, air that are harmful to humans, other living beings or the environment. Pollutants can be Gas, gases like Ground-level ozone, ozone or nitrogen oxides or small particles li ...

. In naegleriasis, "brain-eating" amoeba enter through the olfactory mucosa of the nasal tissues and follow the olfactory nerve fibers into the olfactory bulbs and then the brain.

Additional images

File:Slide21ior.JPG, Olfactory nerve, deep dissection, inferior view

References

External links

* {{Authority control Cranial nerves Olfactory system Otorhinolaryngology Human head and neck Nervous system Neurology Nerves of the head and neck