Sense of Smell
Smell is the least understood of our senses. This results partly from the fact that the sense of smell is a sub-jective phenomenon that cannot be studied with ease in lower animals. Another complicating problem is that the sense of smell is poorly developed in human beings in comparison with the sense of smell in many lower animals.
The olfactory membrane, the histology of which is shown in Figure 53–3, lies in the superior part of each nostril. Medially, the olfactory membrane folds down-ward along the surface of the superior septum; later-ally, it folds over the superior turbinate and even over a small portion of the upper surface of the middle turbinate. In each nostril, the olfactory membrane has a surface area of about 2.4 square centimeters.
Olfactory Cells. The receptor cells for the smell sensa-tion are the olfactory cells (see Figure 53–3), which are actually bipolar nerve cells derived originally from the central nervous system itself. There are about 100 million of these cells in the olfactory epithelium inter-spersed among sustentacular cells, as shown in Figure 53–3. The mucosal end of the olfactory cell forms a knob from which 4 to 25 olfactory hairs (also called olfactory cilia), measuring 0.3 micrometer in diameterand up to 200 micrometers in length, project into the mucus that coats the inner surface of the nasal cavity. These projecting olfactory cilia form a dense mat in the mucus, and it is these cilia that react to odors in the air and stimulate the olfactory cells, as discussed later. Spaced among the olfactory cells in the olfactory membrane are many small Bowman’s glands that secrete mucus onto the surface of the olfactory membrane.
Mechanism of Excitation of the Olfactory Cells. The portionof each olfactory cell that responds to the olfactory chemical stimuli is the olfactory cilia. The odorant sub-stance, on coming in contact with the olfactory mem-brane surface, first diffuses into the mucus that covers the cilia. Then it binds with receptor proteins in the membrane of each cilium. Each receptor protein is actually a long molecule that threads its way through the membrane about seven times, folding inward and outward. The odorant binds with the portion of the receptor protein that folds to the outside. The inside of the folding protein, however, is coupled to a so-called G-protein, itself a combination of three sub-units. On excitation of the receptor protein, an alpha subunit breaks away from the G-protein and immedi-ately activates adenylyl cyclase, which is attached to the inside of the ciliary membrane near the receptor cell body. The activated cyclase, in turn, converts many molecules of intracellular adenosine triphosphate into cyclic adenosine monophosphate (cAMP). Finally, thiscAMP activates another nearby membrane protein, a gated sodium ion channel, that opens its “gate” andallows large numbers of sodium ions to pour through the membrane into the receptor cell cytoplasm. The sodium ions increase the electrical potential in the pos-itive direction inside the cell membrane, thus exciting the olfactory neuron and transmitting action poten-tials into the central nervous system by way of the olfactory nerve.
The importance of this mechanism for activating olfactory nerves is that it greatly multiplies the excita-tory effect of even the weakest odorant.To summarize: (1) Activation of the receptor protein by the odorant substance activates the G-protein complex. (2) This, in turn, activates multiple molecules of adenylyl cyclase inside the olfactory cell membrane. (3) This causes the formation of many times more molecules of cAMP. (4) Finally, the cAMP opens still many times more sodium ion channels. Therefore, even the most minute con-centration of a specific odorant initiates a cascading effect that opens extremely large numbers of sodium channels. This accounts for the exquisite sensitivity of the olfactory neurons to even the slightest amount of odorant.
In addition to the basic chemical mechanism by which the olfactory cells are stimulated, several phys-ical factors affect the degree of stimulation. First, only volatile substances that can be sniffed into the nostrils can be smelled. Second, the stimulating substance must be at least slightly water soluble so that it can pass through the mucus to reach the olfactory cilia. Third, it is helpful for the substance to be at least slightly lipid soluble, presumably because lipid con-stituents of the cilium itself are a weak barrier to non-lipid-soluble odorants.
Membrane Potentials and Action Potentials in Olfactory Cells.
The membrane potential inside unstimulated olfactory cells, as measured by microelectrodes, averages about –55 millivolts. At this potential, most of the cells gen-erate continuous action potentials at a very slow rate, varying from once every 20 seconds up to two or three per second.
Most odorants cause depolarization of the olfactory cell membrane, decreasing the negative potential in the cell from the normal level of –55 millivolts to –30 millivolts or less—that is, changing the voltage in the positive direction. Along with this, the number of action potentials increases to 20 to 30 per second, which is a high rate for the minute olfactory nerve fibers.
Over a wide range, the rate of olfactory nerve impulses changes approximately in proportion to the logarithm of the stimulus strength, which demon-strates that the olfactory receptors obey principles of transduction similar to those of other sensory receptors.
Adaptation. The olfactory receptors adapt about 50 percent in the first second or so after stimulation. There-after, they adapt very little and very slowly. Yet we all know from our own experience that smell sensations adapt almost to extinction within a minute or so after entering a strongly odorous atmosphere. Because this psychological adaptation is far greater than the degree of adaptation of the receptors themselves, it is almost certain that most of the additional adaptation occurs within the central nervous system. This seems to be true for the adaptation of taste sensations as well.
A postulated neuronal mechanism for the adapta-tion is the following: Large numbers of centrifugal nerve fibers pass from the olfactory regions of the brain backward along the olfactory tract and terminate on special inhibitory cells in the olfactory bulb, the granule cells. It has been postulated that after the onsetof an olfactory stimulus, the central nervous system quickly develops strong feedback inhibition to sup-press relay of the smell signals through the olfactory bulb.
Search for the Primary Sensations of Smell
In the past, most physiologists were convinced that the many smell sensations are subserved by a few rather discrete primary sensations, in the same way that vision and taste are subserved by a few select primary sensations. Based on psychological studies, one at-tempt to classify these sensations is the following:
It is certain that this list does not represent the true primary sensations of smell. In recent years, multiple clues, including specific studies of the genes that encode for the receptor proteins, suggest the existence of at least 100 primary sensations of smell—a marked contrast to only three primary sensations of color detected by the eyes and only four or five primary sensations of taste detected by the tongue. Further support for the many primary sensations of smell is that people have been found who have odor blindness for single substances; such discrete odor blindness has been identified for more than 50 different substances. It is presumed that odor blindness for each substance represents lack of the appropriate receptor protein in olfactory cells for that particular substance.
“Affective Nature of Smell.” Smell, even more so thantaste, has the affective quality of either pleasantness or unpleasantness. Because of this, smell is probably evenmore important than taste for the selection of food. Indeed, a person who has previously eaten food that disagreed with him or her is often nauseated by the smell of that same food on a second occasion.Conversely, perfume of the right quality can wreak havoc with human emotions. In addition, in some lower animals, odors are the primary excitant of sexual drive.
Threshold for Smell. One of the principal characteristicsof smell is the minute quantity of stimulating agent in the air that can elicit a smell sensation. For instance, the substance methylmercaptan can be smelled when only one 25 trillionth of a gram is present in each mil-liliter of air. Because of this very low threshold, this substance is mixed with natural gas to give the gas an odor that can be detected when even small amounts of gas leak from a pipeline.
Gradations of Smell Intensities. Although the thresholdconcentrations of substances that evoke smell are extremely slight, for many (if not most) odorants, con-centrations only 10 to 50 times above the threshold evoke maximum intensity of smell. This is in contrast to most other sensory systems of the body, in which the ranges of intensity discrimination are tremendous— for example, 500,000 to 1 in the case of the eyes and 1 trillion to 1 in the case of the ears. This difference might be explained by the fact that smell is concerned more with detecting the presence or absence of odors rather than with quantitative detection of their intensities.