Olfaction

Olfactory perception

Olfaction (the sense of smell) is one of the five senses originally described by Aristotle. It is one of two senses that detect chemicals, the other being taste. Olfaction is the detection of chemicals dissolved in air. The chemicals themselves are called odors or odorants. The sense of smell is also important to the perception of flavor.

Overview of the process of olfaction

A volatile chemical is either carried in the air to the external nostrils and then to the nasal receptors (orthonasal route). This is the pathway that is most used in olfactory perception. Alternatively,an odorant enters into the mouth and then diffuses through the nasopharynx to the nasal receptors and then out the nostrils (retronasal route ).

The nasal receptors are located on cilia in the nasal mucosa (see diagram). The odorant molecules interact with the odor receptors on these cilia in a way which continues to defy scientists. This process of give-and-take interaction , whether it is a lock-and-key type or vibrational tunneling or some other process is still debated hotly .

Once the odorant has been bound to a matching receptor(s), a neural signal is produced which travels along the receptor axon through the cribiform layer of the ethmoidal bone to the glomerular enlargement of the mitral cells which lie in the olfactory bulb. These cells produce a signal which is modified by several other cell types until it is sent down the olfactory nerve tract to several brain areas where it can be consciously perceived,catalogued, put into memory and linked with other perceived sensations.

Receptors

receptor anatomy

Covering the roof of the nasal cavity of human beings lie two separate regions of nasal epithelium, each measuring only 2.5 cm² but containing a total of 10-50 million receptor cells based on estimates of various authors. This layer extends along the superior concha forming a pseudostratified columnar ciliated epithelium composed of three types of cells: (1) olfactory receptor cells ,(2) basal cells and (3) supporting cells. Before odorous compounds can reach the nasal epithelium they must pass through a 60 micron layer of mucous which is secreted by Bowman's glands. Within this mucous layer lie the nonmotile cilia of the olfactory receptor neurons. Each cell contains 8-20 cilia with lengths from 30 to 200 microns (Leffingwell 2002). It is upon these olfactory receptor cilia,lying within the mucous layer, that odorants are detected and a neural signal is initiated.

The basal cells are transformed over a period of about 40 days to become olfactory receptor cells (Leffingwell 2002). This is a rare instance of healthy neurons dying and being replaced by the transformation of non nervous cells at regular intervals.

The trigeminal nerve or cranial nerve V, is also involved in olfactory perception. Compounds creating a cooling sensation such as menthol and camphor as well as compounds creating a hot sensation such as capsaicin will produce a response in the trigeminal nerve.

interaction of receptor and odorant

Human beings can detect thousands of different odors. The exact number of odorant molecules that can be detected is not known but one often hears estimates of 10,000. The number of synthetic molecules producing odors would appear to be almost unlimited.

Each odorant molecule must be small enough to be volatile. No one has described an odor-producing molecule with a molecular weight greater than 294. This appears to be the size limit for a molecule to have sufficient volatility to be detected by the nasal receptors.

Each olfactory receptor neuron (cell) in the nose interacts with only one specific characteristic of an odorant. Odor receptor nerve cells may function like a multiple lock and key system so that when any part of a specific molecule (a key) can fit into the receptor (lock) the nerve cell will be triggered and a specific odor will be perceived. Any given aroma probably interacts with several different types of receptors. The combination of receptor types that are triggered produces an odor perception specific to that molecule.

According to shape theory, each receptor detects a feature of the odor molecule. Weak-shape theory, known as odotope theory, suggests that different receptors detect only small pieces of molecules, and these minimal inputs are combined to create a larger olfactory perception (similar to the way visual perception is built up of smaller, information-poor sensations, combined and refined to create a detailed overall perception).

An alternative theory, the vibration theory proposed by Luca Turin(1996, 2002), proposes that odor receptors detect the frequencies of vibrations of odor molecules in the infrared range by inelastic electron tunnelling (Turin 2005).

Mammals have about 1,000 genes linked to odor reception . But only a small portion of these genes make functional polypeptides involved in odor detection. Humans have 347 functional odor receptor genes; the other genes (pseudogenes) are nonsense mutations. Each gene makes one specific type of receptor (Buck et al. 1991). This number will vary among ethnic groups and among individuals. For example, not all people can smell androstenone, a component of male and female sweat.

If each human odor receptor gene makes a different receptor and if each olfactory receptor neuron responds like a lock and key to a single odorant molecule then we would have the ability to detect only 347 different odors. However, thousands of different aromas are differentiated by only a few hundred receptors. It seems that a single odorant must trigger several different receptors and that each receptor must be able to respond to more than one type of odorant.

Receptor neuron chemistry

In the process of smelling, the binding of the odor molecule to the receptor cell leads to an action potential in the receptor neuron. In mammals , when the odorant and the receptor interact,several changes occur in the interior of the receptor cell. These events are summarized as follows:

1. receptor and odorant have a positive interaction
2. the receptor protein activates a G - protein
3. the G - protein activates the enzyme adenyl cyclase
4. adenyl cyclase converts ATP to cyclic AMP
5. increased cyclic AMP opens a calcium ion channel
6. calcium ions flow into the cell and trigger chloride ion efflux
7. the receptor neuron becomes depolarized and produces an action potential.

(1) The receptor consists of a large transmembrane protein that is part of the cell membrane of the cilia. It is thought to cross the membrane seven times before it connects to a G-protein.

(2) The so called G - protein gets its name from its ability to bind guanosine triphosphate (GTP) and guanosine diphosphate (GDP). In the resting or inactive state the G-protein binds GDP. When an odorant activates the receptor protein , the G-protein binds GTP and enters an active state.

(3,4) When adenyl cyclase is activated it converts adenosine triphosphate (ATP) to cyclic adenosine monophosphate or cyclic AMP (cAMP). Cyclic AMP acts like an intracellular hormone and is often called a "second messenger" - the "first messenger",in this case, being the odorant.

In some animals there is evidence of cAMP being released as a second messenger for some odorants (i.e. eugenol) and inositol triphosphate being an alternative second messenger for other odorants (i.e. ethyl vanillin) (Leffingwell 2002).

(5,6) Production of cAMP opens an ion channel for calcium ions which produces an influx of calcium ions (Ca++) into the cell causing it to become depolarized. These Ca++ in turn open a calcium - activated chloride channel leading to an efflux of chloride ions (Cl-) and this further depolarises the cell and triggers an action potential.

(7)This action potential travels across this bipolar cell to synapse onto the glomerular dendrite of the mitral cells of the olfactory bulb.

Signal processing in the olfactory lobe

Olfactory bulb layers

Olfactory sensory neurons with identical receptors are spread throughout the sensory epithelium. These bipolar cells send their axons through the ethmoidal bone into the olfactory bulb in bundles of roughly 10-100 axons each. Thus each type of receptor, dispersed throughout the sensory area is reunited with its own kind in bundles to send its signal into the olfactory bulb. This convergence of signals from multiple cells,of the same type, onto a single glomerular cell serves to amplify the response to an aroma. In the case of rabbits,some 26,000 receptor cells converge onto only 200 glomeruli, which then converge onto 25 mitral cells. This results in an amplification of about 1,000:1 (Leffingwell 2002,Jacob 2007).

There are several layers of nerve cells within the nasal area :

1. Olfactory receptor neuron layer
2. Glomerular layer
3. External plexiform layer
4. Mitral cell layer
5. Internal plexiform layer
6. Granule cell layer

This organization of the olfactory bulb is reminiscent of the retinal layers. The major neuronal cells of the olfactory bulb are the mitral cells. Adult human beings have about 50,000 mitral cells in each olfactory bulb (Jacob 2007). The mitral cells send out apical dendrites which form a spherical bulb called a glomerulus. Signals are processed at an intraglomerular level for one specific type of receptor. Signals are also processed at an interglomerular level by periglomerular cells, whose action seems to be primarily inhibitory through the release of gamma amino butyric acid (GABA)(Jacob 2007).

Both mitral cells and tufted cells provide output to higher olfactory cortical centers (Lowe 2004). The tufted cells,lying below the glomerular level often make connections to several adjacent glomeruli.

The granule cell bodies lie in a layer below the mitral cell bodies and they make connections with several different types of mitral cells. The dendrites of the granule cells are covered with GABA-containing spines.

The processing of odorant signals from different types of odors is very complex with a lot of intercellular and intracellular summing and subtraction of multiple signal inputs. The final signal perceived as an odor is the result of multiple amplification and or inhibition involving many types of neuronal cells.

Central Pathways of Olfaction

Olfactory bipolar sensory neurons send axons to the mitral cell dendrites (glomeruli) and the tufted cells. The final output of the olfactory bulb cells forms the lateral olfactory tract which travels to higher cortical centers of the brain within the olfactory nerve or cranial nerve I. The main destination of the olfactory nerve tract is the primary olfactory cortex ( pyriform cortex) in the medial temporal lobe of the brain. The olfactory nerve tracts disobey a general rule followed by sensory systems i.e. they do not pass through the brainstem or thalamus before reaching the cortex (Weedman 1997). Olfactory tracts also travel to the prepyriform cortex , the amygdala, the septal nuclei, the entorhinal cortex,hippocampus and subiculum. Many of these areas are part of the limbic system which is involved in the formation of emotions and memories. The septal nuclei and amygdala are part of the "pleasure center". The hippocampus is associated with the memory and food sensations. Olfactory signals are also sent to the thalamus and the frontal cortex for recognition (Jacob 2007).

In the brain , multiple features of the odor may be combined to form a synthesized olfactory perception. Since olfactory receptors can detect many chemical features of an odor molecule, the combination of features gives the olfactory system a broad range of odors that it can detect.

Quantifying olfaction

Scientists have devised methods for quantifying the intensity of odors, particularly for the purpose of analyzing unpleasant or objectionable odors released by an industrial source into a community. Since the 1800s industrial countries have encountered incidents where an industrial source or landfill produced an airborne odor that created adverse reactions in nearby residents. The basic process to quantify an odor is to measure the amount of dilution with "pure" air that is required before the "bad" air is rendered indistinguishable from the "pure" or reference air. Since each person perceives odor differently, an "odor panel" composed of several different people is assembled, each sniffing the same sample of diluted "bad" air.

An alternative procedure,known as purge and trap involves pumping known volumes of off-smelling air into a trap containing an adsorbant and then desorbing the trap onto a gas chromatographic column. This allows one to anlayze the composition of the odor as well as determine its concentration.

A third procedure called solid phase microextraction (S.P.M.E.) involves inserting a needle coated with a selective adsorbant into a sample of air for a fixed period of time and then inserting the needle into the hot inlet of a gas chromatograph/mass spectrometer,where it desorbs onto the column and provides qualitative and quantitative information about all the odorants collected.

The intensity of an odor does not appear to be determined in the same way as odorant character . It may be the result of the strength of the binding of the odorant to the receptor (Turin et al. 2003).

Many air management districts in the USA have numerical standards of acceptability for the intensity of odor that is allowed to cross into a residential property. The Bay Area Air Quality Management District has applied its standard in regulating numerous industries, landfills and sewage treatment plants in the following areas: (1) San Mateo, California wastewater treatment plant; (2) the Bill Graham ampitheatre,(3) Mountain View, California; and (4) the IT Corporation waste ponds in Martinez, California.

Olfaction and taste

Olfaction, taste and trigeminal nerve receptors together contribute to flavor. The human tongue can only distinguish among five distinct types of taste: (1) sweet,(2) salty,(3) sour,(4) bitter and (5) umami; while the nose can distinguish among thousands of substances, even in minute quantities.

Disorders of Olfaction

• Hyposmia: Decreased ability to smell
• Anosmia: Lack of ability to smell
• Phantosmia: smelling things,often unpleasant , which have no visible source
• Dysosmia: Things smell differently than they should (Hirsch, 2003)

Olfaction in animals

The importance and sensitivity of smell varies among different organisms; most mammals have a good sense of smell. Cats have five times more surface area of nasal epithelium than human beings and dogs have forty times more surface area than people (Berg 2004).

Among mammals,the sense of smell is especially well developed in the carnivores and ungulates, who must always be aware of each other, and in those, such as moles and shrews whose eyesight is poor and rely almost entirely on smell to find their food.

Dogs in general have a sense of smell approximately a hundred thousand to a million times more sensitive than a human's. Scenthounds as a group can smell one to ten million times more acutely than a human, and the bloodhound, which has the keenest sense of smell of any dog, has a nose ten to a hundred million times more sensitive than a human's. It was bred for the specific purpose of tracking human beings, and can detect a scent trail a few days old. The second most sensitive nose is possessed by the basset hound, which was bred to track and hunt rabbits and other small animals.

The sense of smell is less developed in the catarrhine primates , and nonexistent in cetaceans, which compensate with a well-developed sense of taste. In some prosimians, such as the Red-bellied Lemur, scent glands occur atop the head. In many species, olfaction is highly tuned to pheromones;

Most birds do not,have a good sense of smell, with the exception of the tubenoses (e.g., petrels and albatrosses) and the kiwi.

Pheromonal olfaction

Some pheromones are detected by the olfactory system, although in many vertebrates, pheromones are also detected by the vomeronasal organ, located in the vomer, between the nose and the mouth. Snakes use it to smell prey, sticking their tongue out and touching it to the organ. Some mammals make a face called flehmen to direct air to this organ.

Smell in insects

A male silkworm moth, can sense a single molecule of bombykol,a pheromone released by the female moth.

Schematic of the olfactory system of insects

In insects , smells are sensed by sensilla located on the antennae and first processed by the antennal lobe (analogous to the olfactory bulb), and next by the mushroom bodies.

Insects use their antennae primarily for olfaction. Sensory neurons in the antenna generate odor-specific electrical signals in response to odour. They process these signals from the sensory neurons in the antennal lobe followed by the mushroom body and lateral horn of the brain. The antennae have the sensory neurons in the sensilla and they have their axons terminating in the antennal lobes where they synapse with other neurons there in glomeruli. These antennal lobes have two kinds of neurons, projection neurons (excitatory) and local neurons (inhibitory). The projection neurons send their axon terminals to the mushroom body and the lateral horn (both of which are part of the protocerebrum).

Local neurons have no axons. Recordings from projection neurons show, in some insects, strong specialization and discrimination for the odors presented (especially for the projection neurons of the macroglomeruli - a specialized complex of glomeruli responsible for pheromone detection). Processing beyond this level is not exactly known ,though some preliminary results are available.

References

ISBN links support NWE through referral fees

• Berg,B. 2004."The scent of surprise" [1]
• Buck, L.and R. Axel. 1991. A Novel Multigene Family May Encode Odorant Receptors: A Molecular Basis for Odor Recognition. Cell 65:175-183.
• Hirsch, Alan R. (2003) Life's a Smelling Success

• Jacob,T. 2007. Olfaction. last viewed on Feb. 2007[2]
• Leffingwell,J.C. 2002. Olfaction - Update No. 5[3]
• Lowe,G. 2004. The Olfactory Bulb. [4]last viewed on 2/15/07
• Nagele. 2002. Lectures on the olfactory epithelium [5]
• Turin, Luca. 1996. A spectroscopic mechanism for primary olfactory reception. Chemical Senses, 21, 773-791.
• Turin, Luca. 2002 A method for the calculation of odor character from molecular structure. Journal of Theoretical Biology, 216, 367-385.
• Turin,Luca 2005. Rational odorant design.pp 261-272 in "Chemistry and Technology of Flavours and Fragrances",ed. David Rowe,Oxford,U.K.,Blackwell publishing[6]
• Turin,L. and F.Yoshii. 2003.Structure-odor relations:a modern perspective. Handbook of olfaction and gustation.Second edition.R.L.Doty editor. New York:Marcel Dekker [7]
• Weedman,D. 1997. Neuroscience Tutorial.[8]

See also

• Machine olfaction
• Presbyosmia

External links

• http://www.thenakedscientists.com/HTML/Columnists/peterbrennancolumn.htm Smells and Odours - How Smell Works]
• http://www.cf.ac.uk/biosi/staff/jacob/teaching/sensory/olfact1.html Olfaction]
• http://www.thenakedscientists.com/HTML/Columnists/peterbrennancolumn2.htm The importance of smell, and pheromones, to Humans and other Animals]
• Structure-odor relations: a modern perspective (PDF)
• Olfactory network dynamics and the coding of multidimensional signals (PDF)
• Chirality & Odour Perception
• Keller, A and Vosshall, LB. (2004). A psychophysical test of the vibration theory of olfaction. Nature Neuroscience 7:337-338. See also the editorial on p. 315.

• ScienceDaily Artille 08/03/2006, Quick — What's That Smell? Time Needed To Identify Odors Reveals Much About Olfaction
• Stopfer, M, Jayaraman, V, Laurent, G (2003) Intensity versus Identity Coding in an Olfactory System, Neuron 39, 991-1004.
• Stopfer, M. and Laurent, G. (1999). Short-term memory in olfactory network dynamics, Nature 402, 664-668.

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