13 May 2009

The sense of smell is the oldest of the senses

The sense of smell gives us the opportunity to enjoy pleasant smells, and sometimes it can save our lives: do not let us drink vinegar instead of vodka, suggest that you should not eat a pie with rotten meat or remind us that when you smell gas, you can not flip the switch. However, the smells around us have properties that many may not even suspect.

Something like a human sense of smell exists even in microorganisms: chemotaxis – the ability to move to food sources and away from dangerous substances – is manifested by all mobile unicellular organisms. But let's skip about 3.5 billion years of the evolution of the sense of smell and go straight to mammals and humans.

For many animals, the sense of smell is at least as important a source of information as sight and hearing: any dog lover knows that dogs get lost when they meet a drunk owner: he looks and speaks the same way, but smells completely different! And not from the "exhaust" (the smell of paint, herring, etc. does not have such an effect), but because, along with the rest of the biochemistry, alcohol changes the composition of sweat and, accordingly, the shades of individual smell that are imperceptible to the human nose.

For you and me, the ability to sense and distinguish odors, at first glance, is not so important. Sometimes it even gets in the way: everyone can remember situations when he was ready to give half the kingdom for not feeling the smell of a homeless person who entered the trolleybus or a colleague who had eaten garlic. And although without the pleasure of the smell of flowers, perfumes, food and many other scents, the world would lose a lot, for a person, the sense of smell is in fourth place among the five senses. Due to vision, we receive at least 90% of information about the world around us, and without it, a person uses tactile sensations and hearing to orient in space and recognize living and inanimate objects.

Scientists have recently deciphered the basic mechanisms of the sense of smell. This lag is due not only to an underestimation of the importance of its role in human life, but also to the extreme complexity of the olfactory receptors.

What do we smell?Gordon Shepherd, a professor of neurology at Yale University, the author of the three–volume Neurobiology, which has survived several reprints, and an incomparable expert on the mechanisms of transmission of impulses by synapses of dendritic spines of the olfactory bulb (this is his narrow specialization), began the answer to this question as follows: "It seems to us that we sniff with the nose, but it's all the same, what can I say that we hear with the lobes of our ears."

The nose itself is necessary in order to direct the air containing aromatic molecules to the olfactory epithelium – symmetrical areas of the mucous membrane located deep in the nasal cavity, slightly below eye level.

We feel odors only during inhalation, since the exhaled air passes only through the lower nasal shells and does not come into contact with the respiratory epithelium. With a calm inhalation, only 7-10% of the inhaled air passes near the olfactory epithelium located in the uppermost part of the nasal cavity, therefore, to enhance sensations, it is necessary to inhale as deeply as possible. You can also take an example from animals and "sniff" by taking frequent short breaths in the immediate vicinity of the object being studied, which allows you to concentrate the odorous molecules as much as possible near the olfactory receptors.

Due to the folds resembling ridges in shape, the total area of the olfactory epithelium in humans is 5-10 cm2. At this second boundary of the olfactory system, according to various sources, there are from 10 to 50 million cells that register odors. In animals, their number is usually much larger. For example, the olfactory epithelium of sheep dogs contains up to 220 million receptor cells.

The olfactory receptor is a sensory (sensitive) nerve cell, from which two processes depart. To the nasal cavity is a short dendrite (a sensitive process of a neuron) having at least 10 cilia, the tips of which are located on the very surface of the olfactory epithelium and protrude into the mucus covering it. To the brain is a longer motor (transmitting) process, an axon intertwining with the axons of other olfactory neurons in the filaments of the olfactory nerve passing through the openings of the lattice bone of the skull into the olfactory bulb – the structure of the brain that performs the primary processing of information about odors. The olfactory bulb is the larger the sharper the animal's sense of smell, so it is much larger in sniffer dogs than in a much larger human brain.

From the olfactory bulb, nerve impulses enter the primary and then the higher olfactory areas of the cerebral cortex, forming a conscious sense of the nature and intensity of the smell. The final point of processing odour data is the limbic system, which regulates the emotional and behavioral reactions of the body.

How does it work?Aromatic molecules entering the nasal cavity with an air current dissolve in the mucus covering the olfactory epithelium and interact with receptor proteins contained in the membrane of the cilia of olfactory neurons.

This interaction changes the ionic permeability of the cell membrane and forms an electrical impulse transmitted along the axon of the cell to the olfactory nerve and further, up to the motor neurons of the spinal cord, giving the muscles commands to hold their nose with their fingers and move away – or vice versa.

The specialists who studied the central mechanisms of the olfactory system figured out quite a long time ago, but protein receptors, undoubtedly present on the membranes of dendrites of neurons of the olfactory epithelium, remained elusive for many years. It was only in 1991 that Columbia University scientists Linda Buck and Richard Excel managed to solve this riddle. In 2004, the discovery earned them the Nobel Prize in Physiology or Medicine.

The traditional approach to studying the mechanisms of olfactory receptors was to measure the activity of certain neurons in response to various stimuli. To do this, electrodes were connected to the olfactory nerves of the animals and they were allowed to inhale various substances. As a result, it was only possible to find out that the same neuron can react to different substances, but the mechanisms underlying this process remained unclear for a long time.

Buck and Excel chose a fundamentally new approach – they turned to rapidly developing genetics and began searching for genes whose activity is recorded exclusively in the olfactory epithelium. At first, their experiments were also unsuccessful, which Excel later explained by the existence of a huge number of receptor proteins, the reaction of each of which to a specific smell is too weak to be detected by existing methods.

To cope with this problem, scientists were helped by a scheme invented by the Lhc, which significantly reduced the search area with the help of three assumptions. According to the first assumption, based on the scattered scientific facts available at that time, it was necessary to look only for genes of proteins that have a certain similarity with rhodopsin – a receptor protein due to which an electric pulse is formed in the rods of the retina of the eye, cells that do not distinguish colors, but react to changes in illumination and provide twilight vision. In addition, the desired proteins should belong to the same family, and the genes encoding them should be active exclusively in the cells of the olfactory epithelium.

In rats, there were about a thousand genes that met all three criteria – about 1% of the entire genome. Every hundredth rat gene is involved in the recognition of odors, which indicates the extreme importance of the olfactory system for rodents – close relatives of primates: our branches on the tree of evolution diverged about 25 million years ago. A search in DNA libraries allowed us to find analog genes associated with the primary perception of odors in the genomes of other species (mice, salamanders, catfish, dogs, humans and other animals). However, unlike most animals, in which most of these genes regularly synthesize the corresponding proteins, 28-36% of the genes of olfactory receptor proteins are inactive in different species of great apes, and almost 60% in humans. Apparently, mutations blocking the activity of olfactory receptor genes began to accumulate from the time when acute sense of smell lost its importance for the survival of ape-like human ancestors.

Further study of the olfactory system showed that each individual receptor neuron can recognize many odorous molecules, each of which activates different protein receptors on the surface of its membrane. Such a combinatorial signal coding system makes it possible to recognize an almost unlimited number of flavors.

Even molecules that differ slightly in chemical structure activate various combinations of receptor proteins located on the membranes of different neurons, so the smell of octane alcohol resembles the smell of citrus fruits, and the smell of sweat differs from it only by one additional oxygen atom of octane acid.

A change in the spatial structure of molecules can lead to the same effect. For example, the smells of cumin and curly mint (from the more famous peppermint, it differs in the absence of a cooling sensation and a less pungent smell) provide d-carvone and l-carvone – chiral (from the ancient Greek χειρ – "hand") isomers, molecules with the same chemical composition, differing from each other, like an object from its mirror image.

In addition, a larger number of molecules activates a wider range of receptors, which is why the same substance can smell differently depending on the concentration.

The most amazing example is skatol, a heterocyclic compound formed during the decomposition of protein compounds and giving a specific smell to feces. At the same time, in small concentrations, skatol has a pleasant smell and is part of perfume products and food essences.

The most versatile in this respect are aldehydes. So, coconut aldehyde in a small concentration does not smell like coconut, but apricot or peach, and the smell of aniseed aldehyde when diluted feels like the aroma of fresh hay, rosehip and hawthorn flowers.

The most unpleasant–smelling compounds include sulfur-containing substances, starting with the simplest - hydrogen sulfide H 2 S. Mercaptans are considered "champions" among them. Their mixture provides the stink of a skunk jet, from which a person can faint. Mercaptans give a unique flavor to rotten cabbage and household gas: natural gas does not smell of anything, and for safety reasons, a little isoamyl mercaptan is added to it. Sulfur–containing compounds diallyl disulfide (CH 2=CH–CH 2)2 S 2 and allicin CH 2=CH–CH 2–SO-S–CH 2–CH=CH 2 provide a pungent smell of garlic, and the main component of onion odor is allylpropyl disulfide CH 2=CH–CH 2–S–S–CH 2–CH–CH 3. Garlic and onion themselves (belonging to the genus Allium) do not contain allyls: when cut, numerous amino acid cysteine molecules containing sulfhydryl groups –SH are converted into them under the action of enzymes. The peculiarity of these disulfides is that it is almost impossible to get rid of the smell either by brushing your teeth or rinsing your mouth. The fact is that these compounds, having penetrated through the intestinal walls into the blood, are carried throughout the body, including into the lungs, from where they are released with exhaled air.

The sense of smell in our livesThe most important thing is the sense of smell in the first minutes of a person's life, since it is only thanks to him that the baby recognizes his mother and finds a breast smelling of milk.

In the next couple of months, until the child's eyesight acquires sufficient acuity, he perceives the world around him mainly through smells. As they grow up and form other senses, the sense of smell loses its significance. At the same time, atrophy (death) of the olfactory nerve fibers occurs. During the first year of life, the acuity of a person's sense of smell decreases by 40-50%, and the further rate and degree of deterioration of the ability to recognize odors depends on the individual characteristics of the body, gender, lifestyle and exposure to various environmental factors. For example, in novice smokers, the ability to distinguish odors decreases by 50-60%, after which it is restored by 20-30%. When quitting smoking, hyperosmia develops – the acuity of the sense of smell increases by about 20% compared to the initial one.

It is believed that a person is more sensitive to unpleasant odors. Almost always, we perceive odors that signal danger as unpleasant: do not eat rotten meat or rotten fruits, stay away from hydrogen sulfide, chlorine, ammonia, do not get into excrement – they may contain worm eggs, dysentery amoebas and other cholera... Those of our ancestors (still covered with scales, not wool) who did not have such associations were eliminated by natural selection. Although there are exceptions – for example, garlic, which completely falls under the folk proverb "it doesn't smell its own" :)

However, the substances that we can feel in the lowest concentrations smell nice. Vanillin was considered a record holder for a long time: it can be smelled at a concentration of 2 × 10-11 g in a liter of air. But more recently it turned out that one of the chiral isomers of a substance called wine lactone (it gives wines a sweet coconut flavor) is felt at a concentration two thousand times less: one hundred trillion (10-14)grams in 1 liter of air. And the smell of its mirror isomer (in the figure on the right) can be felt only at a concentration 11 orders of magnitude higher – 1 mg / l.

Women in general have a sharper sense of smell, which persists until a more advanced age. However, paradoxically, the professions associated with the distinction of odors are exclusively male. The fact is that changes in the hormonal background during the monthly cycles of the female body affect the work of various organs and systems, including the olfactory system. As a result, at the beginning of the cycle, women often develop temporary hyposmia – a decrease in sensitivity to odors. This is not observed when taking hormonal contraceptives that maintain a constant hormonal background in the body, but it is obvious that taking pills cannot be a prerequisite for employment.

Without the sense of smell, our food would become almost tasteless. Human taste buds distinguish only four sensations: sweet, salty, sour and bitter, and the rest of the variety of tastes of various dishes and drinks is provided by combinations of aromatic substances. With a strong runny nose, when the upper nasal conchs are "clogged" and the air containing aromas simply does not reach them, everything seems tasteless and unappetizing. Experiments have shown that if a person with a pinched nose is also blindfolded to deprive him of visual associations with the products he uses, he is unlikely to be able to distinguish an apple from a potato or red wine from coffee.

Odors can change the work of various body systems. The most obvious example is the increased production of saliva and digestive juices from food odors. Sharp and unpleasant odors (for example, ammonia) increase blood pressure and accelerate the heartbeat, while pleasant ones, on the contrary, reduce pressure, slow down the pulse and cause an increase in skin temperature, which relaxes and soothes a person.

How well–founded are the claims of aromatherapists - for example, this: "the aromas of lavender, chamomile, lemon and sandalwood weaken the activity of the brain faster than any depressant, and jasmine, rose, mint and clove excite the cells of gray matter more powerfully than strong coffee"? Judging by the fact that in the articles of different authors one can find directly opposite statements about the effect of odors on the psychophysiological state of a person, this action is explained not by the nature of the smell itself, but by the psychological attitude to the expected effect.

Another, perhaps, the most mysterious question in the science of odors is their role in the sexual behavior of Homo sapiens. We will talk about this in the next article.

Evgeniya Ryabtseva,
portal "Eternal youth" www.vechnayamolodost.ru

The journal version of the article was published in Popular Mechanics No. 5-2009

13.05.2009

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