WK3

 cutaneous sense ( kew  tane  ee us ) One of the somatosenses; includes sensitivity to stimuli that involve the skin.

 proprioception Perception of the body’s position and posture.

 kinesthesia Perception of the body’s own movements.

 organic sense A sense modality that arises from receptors located within the inner organs of the body.

The Stimuli

The cutaneous senses respond to several different types of stimuli: pressure, vibration, heating, cooling, and events that cause tissue damage (and hence pain). Feelings of pressure are caused by mechanical deformation of the skin. Vibration is produced in the laboratory or clinic by tuning forks or mechanical devices, but it more commonly occurs when we move our fingers across a rough surface. Thus, we use vibration sensitivity to judge an object’s roughness. Obviously, sensations of warmth and coolness are produced by objects that raise or lower skin temperature from normal. Sensations of pain can be caused by many different types of stimuli, but it appears that most cause at least some tissue damage.

One source of kinesthesia is the stretch receptors found in skeletal muscles that report changes in muscle length to the central nervous system. Receptors within joints between adjacent bones respond to the magnitude and direction of limb movement. However, the most important source of kinesthetic feedback appears to come from receptors that respond to changes in the stretching of the skin during movements of the joints or of the muscles themselves, such as those in the face (Johansson and Flanagan,  2009 ). Muscle length detectors, located within the muscles, do not give rise to conscious sensations; their information is used to control movement. These receptors will be discussed separately in  Chapter 8 .

We are aware of some of the information received by means of the organic senses, which can provide us with unpleasant sensations such as stomachaches or gallbladder attacks, or pleasurable ones such as those provided by a warm drink on a cold winter day. We are unaware of some information, such as that provided from receptors in the digestive system, kidneys, liver, heart, and blood vessels that are sensitive to nutrients and minerals. This information, which plays a role in the control of metabolism and water and mineral balance, is described in  Chapter 12 .

Anatomy of the Skin and Its Receptive Organs

The skin is a complex and vital organ of the body—one that we tend to take for granted. We cannot survive without it; extensive skin burns are fatal. Our cells, which must be bathed by a warm fluid, are protected from the hostile environment by the skin’s outer layers. The skin participates in thermoregulation by producing sweat, thus cooling the body, or by restricting its circulation of blood, thus conserving heat. Its appearance varies widely across the body, from mucous membrane to hairy skin to the smooth, hairless skin of the palms and the soles of the feet, which is known as  glabrous skin . (The word derives from the Latin glaber, “smooth, bald.”) Skin consists of subcutaneous tissue, dermis, and epidermis and contains various receptors scattered throughout these layers. Glabrous skin contains a dense, complex mixture of receptors, which reflects the fact that we use the palms of our hands and the inside surfaces of our fingers to actively explore the environment: We use our hands and fingers to hold and touch objects. In contrast, the rest of our body most often contacts the environment passively; that is, other things come into contact with it.

 glabrous skin (glab  russ ) Skin that does not contain hair; found on the palms and the soles of the feet.

Figure 7.25  shows the appearance of free nerve endings and the four types of encapsulated receptors ( Merkel’s disks ,  Ruffini corpuscles ,  Meissner’s corpuscles , and  Pacinian corpuscles ). The locations and functions of these receptors are listed in  Table 7.1 . (See  Figure 7.25  and  Table 7.1 . )

 Merkel’s disk A touch-sensitive cutaneous receptor, important for detection of form and roughness, especially by fingertips.

 Ruffini corpuscle A touch-sensitive cutaneous receptor, important in detecting stretching or static force against the skin, important in proprioception.

 Meissner’s corpuscle A touch-sensitive cutaneous receptor, important in detecting edge contours or Braille-like stimuli, especially by fingertips.

 Pacinian corpuscle ( pa  chin  ee un ) A vibration-sensitive cutaneous receptor, important in detecting vibration from an object being held.

FIGURE 7.25 Cutaneous Receptors

Perception of Cutaneous Stimulation

The three most important qualities of cutaneous stimulation are touch, temperature, and pain. These qualities, along with itch, are described in the sections that follow.

TOUCH

Stimuli that cause vibration in the skin or changes in pressure against it (tactile stimuli) are detected by  mechanoreceptors —the encapsulated receptors shown in  Figure 7.25  and some types of free nerve endings. Most investigators believe that the encapsulated nerve endings serve only to modify the physical stimulus transduced by the dendrites that reside within them. But what is the mechanism of transduction? How does movement of the dendrites of mechanoreceptors produce changes in membrane potentials? It appears that the movement causes ion channels to open, and the flow of ions into or out of the dendrite causes a change in the membrane potential. You will recall that TRPA1, a member of the TRP (transient receptor potential) family of receptor proteins, is responsible for transduction of mechanical information in auditory and vestibular hair cells.

 mechanoreceptor A sensory neuron that responds to mechanical stimuli: for example, those that produce pressure, stretch, or vibration of the skin or stretch of muscles or tendons.

Most information about tactile stimulation is precisely localized—that is, we can perceive the location on our skin where we are being touched. However, a study by Olausson et al. ( 2002 ) discovered a new category of tactile sensation.

TABLE 7.1 Categories of Cutaneous Receptors

At age 31, patient G. L., a 54-year-old woman, had “suffered a permanent and specific loss of large myelinated afferents after episodes of acute polyradiculitis and polyneuropathy that affected her whole body below the nose. A sural nerve biopsy indicated a complete loss of large-diameter myelinated fibers. . . . Before the present study, she denied having any touch sensibility below the nose, and she lost the ability to perceive tickle when she became ill. She states that her perceptions of temperature, pain and itch are intact” (Olausson et al.,  2002 , pp. 902–903).

G. L. could indeed detect the stimuli that are normally attributed to small-diameter unmyelinated axons—temperature, pain, and itch—but she could not detect vibratory or normal tactile stimuli. But when the hairy skin on her forearm or the back of her hand was stroked with a soft brush, she reported a faint, pleasant sensation. However, she could not determine the direction of the stroking or its precise location. An fMRI analysis showed that this stimulation activated the insular cortex, a region that is known to be associated with emotional responses and sensations from internal organs. The somatosensory cortex was not activated. When regions of hairy skin of control subjects were stimulated this way, fMRI showed activation of the primary and secondary somatosensory cortex as well as the insular cortex because the stimulation activated both large and small axons. The glabrous skin on the palm of the hand is served only by large-diameter, myelinated axons. When this region was stroked with a brush, G. L. reported no sensation at all, presumably because of the absence of small, unmyelinated axons.

The investigators concluded that, besides conveying information about noxious and thermal stimuli, small-diameter unmyelinated axons constitute a “system for limbic touch that may underlie emotional, hormonal and affiliative responses to caresslike, skin-to-skin contact between individuals” (Olausson et al.,  2002 , p. 900). And, as we saw, G. L. could no longer perceive tickle. Tickling sensations, which were previously believed to be transmitted by these small axons, are apparently transmitted by the large, myelinated axons that were destroyed in patient G. L.

Olausson and his colleagues (Löken et al.,  2009 ) note that the sensory endings that detect pleasurable stroking are found only in hairy skin, and that stroking of glabrous skin does not provide these sensations. However, I can think of pleasurable tactile stimuli that can be experienced through the glabrous skin of the palms and fingers—for example, those provided by stroking a warm, furry animal or touching a baby or a lover. When our hairy skin contacts the skin of another person, it is more likely that that person is touching us. In contrast, when our glabrous skin contacts the skin of another person, it is more likely that we are touching them. Thus, we might expect receptors in hairy skin to provide pleasurable sensations when someone caresses us but expect receptors in glabrous skin to provide pleasurable sensations when we caress someone else.

Our cutaneous senses are used much more often to analyze shapes and textures of stimulus objects that are moving with respect to the surface of the skin. Sometimes, the object itself moves; but more often, we do the moving ourselves. If I placed an object in your palm and asked you to keep your hand still, you would have a great deal of difficulty recognizing the object by touch alone. If I said that you could now move your hand, you would manipulate the object, letting its surface slide across your palm and the pads of your fingers. You would be able to describe the object’s three-dimensional shape, hardness, texture, slipperiness, and so on. Obviously, your motor system must cooperate, and you need kinesthetic sensation from your muscles and joints, besides the cutaneous information. If you squeeze the object and feel a lot of well-localized pressure in return, it is hard. If you feel a less intense, more diffuse pressure in return, it is soft. If it produces vibrations as it moves over the ridges on your fingers, it is rough. If very little effort is needed to move the object while pressing it against your skin, it is slippery. If it does not produce vibrations as it moves across your skin, but moves in a jerky fashion, and if it takes effort to remove your fingers from its surface, it is sticky. Thus, our somatosenses work dynamically with the motor system to provide useful information about the nature of objects that come into contact with our skin.

Studies of people who make especially precise use of their fingertips show changes in the regions of somatosensory cortex that receive information from this part of the body. For example, violinists must make very precise movements of the four fingers of the left hand, which are used to play notes by pressing the strings against the fingerboard. Tactile feedback and proprioceptive feedback are very important in accurately moving and positioning these fingers so that sounds of the proper pitch are produced. In contrast, placement of the thumb, which slides along the bottom of the neck of the violin, is less critical. In a study of violin players, Elbert et al. ( 1995 ) found that the portions of their right somatosensory cortex that receive information from the four fingers of their left hand were enlarged relative to the corresponding parts of the left somatosensory cortex. The amount of somatosensory cortex that receives information from the thumb was not enlarged. (The right hand holds the bow, and the violist makes precise movements with the arm and wrist, but tactile information from the fingers of this hand is much less important.)

TEMPERATURE

Feelings of warmth and coolness are relative, not absolute, except at the extremes. There is a temperature level that, for a particular region of skin, will produce a sensation of temperature neutrality—neither warmth nor coolness. This neutral point is not an absolute value but depends on the prior history of thermal stimulation of that area. If the temperature of a region of skin is raised by a few degrees, the initial feeling of warmth is replaced by one of neutrality. If the skin temperature is lowered to its initial value, it now feels cool. Thus, increases in temperature lower the sensitivity of warmth receptors and raise the sensitivity of cold receptors. The converse holds for decreases in skin temperature. This adaptation to ambient temperature can be demonstrated easily by placing one hand in a bucket of warm water and the other in a bucket of cool water until some adaptation has taken place. If you then simultaneously immerse both hands in water at room temperature, it will feel warm to one hand and cool to the other.

There are two categories of thermal receptors: those that respond to warmth and those that respond to coolness. Cold sensors in the skin are located just beneath the epidermis, and warmth sensors are located more deeply in the skin. Information from cold sensors is conveyed to the CNS by thinly myelinated Aδ fibers, and information from warmth sensors is conveyed by unmyelinated C fibers. We can detect thermal stimuli over a very wide range of temperatures, from less than 8° C (noxious cold) to over 52° C (noxious heat). Investigators have long believed that no single receptor could detect such a range of temperatures, and recent research indicates that this belief was correct. At present we know of six mammalian thermoreceptors—all members of the TRP family (Bandell, Macpherson, and Patapoutian,  2007 ; Romanovsky,  2007 ). (See  Figure 7.26  and  Table 7.2 . )

Some of the thermal receptors respond to particular chemicals as well as to changes in temperature. For example, the M in TRPM8 stands for menthol, a compound found in the leaves of many members of the mint family. As you undoubtedly know, peppermint tastes cool in the mouth, and menthol is added to some cigarettes to make the smoke feel cooler (and perhaps to try to delude smokers into thinking that the smoke is less harsh and damaging to the lungs). Menthol provides a cooling sensation because it binds with and stimulates the TRPM8 receptor and produces neural activity that the brain interprets as coolness. As we will see in the next subsection, chemicals can produce the sensation of heat also.

Bautista et al. ( 2007 ) prepared mice with a targeted mutation (knockout) of the TRPM8 receptor gene. They found that the mutation severely impaired the response of the mice to environmental cold. The investigators assessed sensitivity to cold by placing the mice in a box that contained two chambers connected by an opening through which the animals could pass. The floors of the chambers consisted of temperature-controlled metal plates. Normal mice preferred to spend time on a plate held at 30° C and avoided a 20° C plate. However, the mice without TRPM8 receptors showed no preference until the temperature on the cool plate dropped to 15° C. In addition, electrical recordings of cutaneous C fibers of the mutant mice showed no evidence of cold-sensitive neurons.

FIGURE 7.26 Activity of Thermosensitive Receptors

The activity of cold-activated (blue) and heat-activated (orange) temperature-sensitive TRP channels are shown as a function of temperature.

(Adapted from Romanovsky, A. A. American Journal of Physiology, 2007, 292, R37–R46.)

TABLE 7.2 Categories of Mammalian Thermal Receptors

PAIN

The story of pain is quite different from that of temperature and pressure; pain is a very complicated sensation. It is obvious that our awareness of pain and our emotional reaction to it are controlled by mechanisms within the brain. For example, we can have a tooth removed painlessly under hypnosis, which has no effect on the sensitivity of pain receptors. Stimuli that produce pain also tend to trigger species-typical escape and withdrawal responses. Subjectively, these stimuli hurt, and we try hard to avoid or escape from them. However, sometimes we are better off ignoring pain and getting on with important tasks. In fact, our brains possess mechanisms that can reduce pain, partly through the action of the endogenous opioids. These mechanisms are described in more detail in a later section of this chapter.

Pain reception, like thermoreception, is accomplished by the networks of free nerve endings in the skin. There appear to be at least three types of pain receptors (usually referred to as nociceptors, or “detectors of noxious stimuli”). High-threshold mechanoreceptors are free nerve endings that respond to intense pressure, which might be caused by something striking, stretching, or pinching the skin. A second type of free nerve ending appears to respond to extremes of heat, to acids, and to the presence of capsaicin, the active ingredient in chile peppers. (Note that we say that chile peppers make food taste “hot.”) This type of fiber contains TRPV1 receptors (Kress and Zeilhofer,  1999 ). The V stands for vanilloid—a group of chemicals of which capsaicin is a member. Caterina et al. ( 2000 ) found that mice with a knockout of the gene for the TRPV1 receptor showed less sensitivity to painful high-temperature stimuli and would drink water to which capsaicin had been added. The mice responded normally to noxious mechanical stimuli. Presumably, the TRPV1 receptor is responsible for pain produced by burning of the skin and to changes in the acid/base balance within the skin. These receptors are responsible for the irritating effect of chemicals such as ammonia on the mucous membranes of the nose (Dhaka et al.,  2009 ). TRPV1 receptors also appear to play a role in regulation of body temperature. In addition, Ghilardi et al. ( 2005 ) found that a drug that blocks TRPV1 receptors reduced pain in patients with bone cancer, which is apparently caused by the production of acid by the tumors.

Another type of nociceptive fiber contains TRPA1 receptors, which, as we saw earlier in this chapter, are found in the cilia of auditory and vestibular hair cells. TRPA1 receptors are sensitive to pungent irritants found in mustard oil, wintergreen oil, horseradish, and garlic and to a variety of environmental irritants, including those found in vehicle exhaust and tear gas (Bautista et al.,  2006 ; Nilius et al.,  2007 ). The primary function of this receptor appears to be to provide information about the presence of chemicals that produce inflammation.

ITCH

Another noxious sensation, itch (or, more formally, pruritus) is caused by skin irritation. Itch was defined by a seventeenth-century German physician as an “unpleasant sensation that elicits the desire or reflex to scratch” (Ikoma et al.,  2006 , p. 535.) If an adult sees a child scratching at an insect bite or other form of skin irritation, the adult is likely to say, “Stop that—it will only make it worse!” The scratching may indeed make the irritation worse, but the immediate effect of scratching is to reduce the itching. Davidson et al. ( 2009 ) found that scratching inhibited the activity of neurons in the spinothalamic tract of monkeys that transmit itch sensations to the brain. Presumably, the scratch response to stimuli that produce itching helps rid skin of irritating debris or parasites (Davidson and Giesler,  2010 ). Scratching reduces itching because pain suppresses itching (and, ironically, itching reduces pain). Histamine and other chemicals released by skin irritation and allergic reactions are important sources of itching. Experiments have shown that painful stimuli such as heat and electrical shock can reduce sensations of itch produced by an injection of histamine into the skin, even when the painful stimuli are applied up to 10 cm from the site of irritation (Ward, Wright, and McMahon,  1996 ; Nilsson, Levinsson, and Schouenborg,  1997 ). On the other hand, the administration of an opiate into the epidural space around the spinal cord diminishes pain but often produces itching as an unwelcome side effect (Chaney,  1995 ). Naloxone, a drug that blocks opiate receptors, has been used to reduce cholestatic pruritus, a condition of itching that sometimes accompanies pregnancy (Bergasa,  2005 ).

Little is known about the receptors that are responsible for the sensation of itch, but at least two different types of neurons transmit itch-related information to the CNS. Johanek et al. ( 2007 ) produced itch in volunteers with intradermal injections of histamine and applications of cowhage spicules—tiny, needlelike plant fibers that contain an enzyme that breaks down proteins in the skin. Both treatments produce intense itch, but only histamine produces an area of vasodilation. Pretreatment of a patch of skin with a topical antihistamine prevented histamine from producing an itch at that spot but had no effect on the itch produced by cowhage. In contrast, pretreatment of a patch of skin with capsaicin prevented cowhage-induced itch but not histamine-induced itch.

The Somatosensory Pathways

Somatosensory axons from the skin, muscles, or internal organs enter the central nervous system via spinal nerves. Those located in the face and head primarily enter through the trigeminal nerve (fifth cranial nerve). The cell bodies of the unipolar neurons are located in the dorsal root ganglia and cranial nerve ganglia. Axons that convey precisely localized information, such as fine touch, ascend through the dorsal columns in the white matter of the spinal cord to nuclei in the lower medulla. From there, axons cross the brain and ascend through the medial lemniscus to the ventral posterior nuclei of the thalamus, the relay nuclei for somatosensation. Axons from the thalamus project to the primary somatosensory cortex, which in turn sends axons to the secondary somatosensory cortex. In contrast, axons that convey poorly localized information, such as pain or temperature, form synapses with other neurons as soon as they enter the spinal cord. The axons of these neurons cross to the other side of the spinal cord and ascend through the spinothalamic tract to the ventral posterior nuclei of the thalamus. (See  Figure 7.27 . )

Recall from  Chapter 6  that the primary visual cortex contains columns of cells, each of which responds to particular features, such as orientation, ocular dominance, or spatial frequency. Within these columns are blobs that contain cells that respond to particular colors. The somatosensory cortex also has a columnar arrangement; in fact, cortical columns were discovered there by Mountcastle ( 1957 ) before they were found in the visual and auditory cortex. Within a column, neurons respond to a particular type of stimulus (for example, temperature or pressure) applied to a particular part of the body.

Dykes ( 1983 ) has reviewed research indicating that the primary and secondary somatosensory cortical areas are divided into at least five (and perhaps as many as ten) different maps of the body surface. Within each map, cells respond to a particular submodality of somatosensory receptors. Separate areas have been identified that respond to slowly adapting cutaneous receptors, rapidly adapting cutaneous receptors, receptors that detect changes in muscle length, receptors located in the joints, and Pacinian corpuscles.

As we saw in  Chapter 6 , damage to the visual association cortex can cause visual agnosia, and as we saw earlier in this chapter, damage to the auditory association cortex can cause auditory agnosia. You will not be surprised to learn that damage to the somatosensory association cortex can cause tactile agnosia. Reed, Caselli, and Farah ( 1996 ) described patient E. C., a woman with left parietal lobe damage who was unable to recognize common objects by touch. For example, the patient identified a pine cone as a brush, a ribbon as a rubber band, and a snail shell as a bottle cap. The deficit was not due to a simple loss of tactile sensitivity; the patient was still sensitive to light touch and to warm and cold objects, and she could easily discriminate objects by their size, weight, and roughness.

Nakamura et al. ( 1998 ) described patient M. T., who had a different type of tactile agnosia. Patient M. T. had bilateral lesions of the angular gyrus, a region of the parietal lobe surrounding the caudal end of the lateral fissure. This patient, like patient E. C., had normal tactile sensitivity, but he could not identify objects by touch. However, unlike patient E. C., he could draw objects that he touched even though he could not recognize what they were. (See  Figure 7.28 . ) The fact that he could draw the objects means that his ability to perceive three-dimensional objects by touch must have been intact. However, the brain damage prevented the information analyzed by the somatosensory association cortex to be transmitted to parts of the brain responsible for control of language—and for consciousness.

FIGURE 7.27 Somatosensory Pathways

The figure shows the somatosensory pathways from the spinal cord to the somatosensory cortex. Note that precisely localized information (such as fine touch) and imprecisely localized information (such as pain and temperature) are transmitted by different pathways.

FIGURE 7.28 Tactile Agnosia

(a) Drawings of wrenches felt but not seen by M. T., Although the patient did not recognize the objects as wrenches, he was able to draw them accurately. (b) Drawings of objects felt but not seen by E. C. The patient could neither recognize the objects by touch nor draw them accurately.

(From Nakamura, J., Endo, K., Sumida, T., and Hasegawa, T. Cortex, 1998, 34, 375–388, and Reed, C. L., Caselli, R. J., and Farah, M. J. Brain, 1996, 119, 875–888. Reprinted with permission.)

As I mentioned earlier, recognition of objects by touch requires cooperation between the somatosensory and motor systems. When we attempt to identify objects by touch alone, we explore them with moving fingers. Valenza et al. ( 2001 ) reported the case of a patient with brain damage to the right hemisphere that produced a disorder they called tactile apraxia. As we will see in  Chapter 8 , apraxia refers to a difficulty in carrying out purposeful movements in the absence of paralysis or muscular weakness. When the experimenters gave the patient objects to identify by touch with her left hand, the patient explored the objects with her fingers in a disorganized fashion. (Exploration and identification using her right hand were normal.) If the experimenters guided the patient’s fingers and explored an object the way people normally do, she was able to recognize the object’s shape. Thus, her deficit was caused by a movement disorder, not by damage to brain mechanisms involved in tactile perception.

Perception of Pain

Pain is a curious phenomenon. It is more than a mere sensation; it can be defined only by some sort of withdrawal reaction or, in humans, by verbal report. Pain can be modified by opiates, by hypnosis, by the administration of pharmacologically inert sugar pills, by emotions, and even by other forms of stimulation, such as acupuncture. Recent research efforts have made remarkable progress in discovering the physiological bases of these phenomena.

We might reasonably ask why we experience pain. The answer is that in most cases pain serves a constructive role. For example, inflammation, which often accompanies injuries to skin or muscle, greatly increases sensitivity of the inflamed region to painful stimuli. This effect motivates the individual to minimize movement of the injured part and avoid contact with other objects. The effect is to reduce the likelihood of further injury.

Cox et al. ( 2006 ) studied three families from northern Pakistan whose members included several people with a complete absence of pain and discovered the location of the gene responsible for this disorder. The gene, an autosomal recessive allele located on chromosome 2, encodes for a voltage-dependent sodium channel, Nax1.7. The case that brought the families to their attention was a 10-year-old boy who performed a “street theater” during which he would thrust knives through his arms and walk on burning coals without feeling any pain. He died just before his fourteenth birthday after jumping off the roof of a house. All six of the affected people in the three families had injuries to their lips or tongues caused by self-inflicted bites. They all suffered from bruises and cuts, and many sustained bone fractures that they did not notice until the injuries impaired their mobility. Despite their total lack of pain from any type of noxious stimulus, they had normal sensations of touch, warmth, coolness, proprioception, tickle, and pressure.

Some environmental events diminish the perception of pain. For example, Beecher ( 1959 ) noted that many wounded American soldiers back from the battle at Anzio, Italy, during World War II reported that they felt no pain from their wounds. They did not even want medication. It would appear that their perception of pain was diminished by the relief they felt from surviving such a terrible ordeal. There are other instances in which people report the perception of pain but are not bothered by it. Some tranquilizers have this effect, and damage to parts of the brain does too.

Pain appears to have three different perceptual and behavioral effects (Price,  2000 ). First is the sensory component—the pure perception of the intensity of a painful stimulus. The second component is the immediate emotional consequences of pain—the unpleasantness or degree to which the individual is bothered by the painful stimulus. It is this characteristic that was reduced in some of the soldiers at Anzio. The third component is the long-term emotional implications of chronic pain—the threat that such pain represents to one’s future comfort and well-being.

These three components of pain appear to involve different brain mechanisms. The purely sensory component of pain is mediated by a pathway from the spinal cord to the ventral posterolateral thalamus to the primary and secondary somatosensory cortex. The immediate emotional component of pain appears to be mediated by pathways that reach the anterior cingulate cortex (ACC) and insular cortex. The long-term emotional component appears to be mediated by pathways that reach the prefrontal cortex. (See  Figure 7.29 . )

Let’s look at some evidence for brain mechanisms involved in short-term and long-term emotional responses to pain. Several studies have found that painful stimuli activate the insular cortex and the ACC. In addition, Ostrowsky et al. ( 2002 ) found that electrical stimulation of the insular cortex caused reports of painful burning and stinging sensations. Damage to this region decreases people’s emotional response to pain (Berthier, Starkstein, and Leiguarda,  1988 ): They continue to feel the pain but do not seem to recognize that it is harmful. They do not withdraw from pain or the threat of pain.

Rainville et al. ( 1997 ) produced pain sensations in human subjects by having them put their arms in ice water. Under one condition, the researchers used hypnosis to diminish the unpleasantness of the pain. The hypnosis worked; the subjects said that the pain was less unpleasant, even though it was still as intense. Meanwhile, the investigators used a PET scanner to measure regional activation of the brain. They found that the painful stimulus increased the activity of both the primary somatosensory cortex and the ACC. When the subjects were hypnotized and found the pain less unpleasant, the activity of the ACC decreased, but the activity of the primary somatosensory cortex remained high. Presumably, the primary somatosensory cortex is involved in the perception of pain, and the ACC is involved in its immediate emotional effects—its unpleasantness. (See  Figure 7.30 . )

FIGURE 7.29 The Three Components of Pain

A simplified, schematic diagram shows the brain mechanisms involved in the three components of pain: the sensory component, the immediate emotional component, and the long-term emotional component.

(Adapted from Price, D. B. Science, 2000, 288, 1769–1772.)

In another study from the same laboratory, Hofbauer et al. ( 2001 ) produced the opposite effect. They presented subjects with a painful stimulus and used hypnotic suggestion to reduce the perceived intensity of the pain. They found that the suggestion reduced subjects’ ratings of pain and also decreased the activation of the somatosensory cortex. Thus, changes in perceived intensity of pain are reflected in changes in activation of the somatosensory cortex, whereas changes in perceived unpleasantness of pain is reflected in changes in activation of the ACC.

Several functional-imaging studies have shown that under certain conditions, stimuli associated with pain can activate the ACC even when no actual painful stimulus is applied. Osaka et al. ( 2004 ) found that the ACC was activated when subjects heard Japanese words that vividly denote various types of pain (for example, a throbbing pain, a splitting headache, or the pain caused by being stuck with thorns). In a test of romantically involved couples, Singer et al. ( 2004 ) found that when women received a painful electrical shock to the back of their hand, their ACC, anterior insular cortex, thalamus, and somatosensory cortex became active. When they saw their partners receive a painful shock but did not receive one themselves, the same regions (except for the somatosensory cortex) became active. Thus, the emotional component of pain—in this case, a vicarious experience of pain, provoked by empathy with the feelings of someone a person loved—caused responses in the brain similar to the ones caused by actual pain. Just as we saw in the study by Rainville et al. ( 1997 ), the somatosensory cortex is activated only by an actual noxious stimulus.

The final component of pain—the emotional consequences of chronic pain—appears to involve the prefrontal cortex. As we will see in  Chapter 11 , damage to the prefrontal cortex impairs people’s ability to make plans for the future and to recognize the personal significance of situations in which they are involved. Along with the general lack of insight, people with prefrontal damage tend not to be concerned with the implications of chronic conditions—including chronic pain—for their future.

FIGURE 7.30 Sensory and Emotional Components of Pain

The PET scans show brain regions that respond to pain. Top: Dorsal views of the brain. Activation of the primary somatosensory cortex (circled in red) by a painful stimulus was not affected by a hypnotically suggested reduction in unpleasantness of a painful stimulus, indicating that this region responded to the sensory component of pain. Bottom:Midsagittal views of the brain. The anterior cingulate cortex (circled in red) showed much less activation when the unpleasantness of the painful stimulus was reduced by hypnotic suggestion.

(From Rainville, P., Duncan, G. H., Price, D. D., Carrier, Benoit, and Bushnell, M. C. Science, 1997, 277, 968–971. Copyright © American Association for the Advancement of Science. Reprinted with permission.)

A particularly interesting form of pain sensation occurs after a limb has been amputated. After the limb is gone, up to 70 percent of amputees report that they feel as though the missing limb still exists and that it often hurts. This phenomenon is referred to as the  phantom limb  (Melzak,  1992 ; Ramachandran and Hirstein,  1998 ). People with phantom limbs report that the limb feels very real, and they often say that if they try to reach out with it, it feels as though it were responding. Sometimes, they perceive it as sticking out, and they may feel compelled to avoid knocking it against the side of a doorframe or sleeping in a position that would make it come between them and the mattress. People have reported all sorts of sensations in phantom limbs, including pain, pressure, warmth, cold, wetness, itching, sweatiness, and prickliness.

 phantom limb Sensations that appear to originate in a limb that has been amputated.

The classic explanation for phantom limbs has been activity of the sensory axons belonging to the amputated limb. Presumably, the nervous system interprets this activity as coming from the missing limb. When nerves are cut and connections cannot be reestablished between the proximal and distal portions, the cut ends of the proximal portions form nodules known as neuromas. The treatment for phantom pain has been to cut the nerves above these neuromas, to cut the dorsal roots that bring the afferent information from these nerves into the spinal cord, or to make lesions in somatosensory pathways in the spinal cord, thalamus, or cerebral cortex. Sometimes these procedures work for a while, but often the pain returns.

Melzak ( 1992 ) suggested that the phantom limb sensation is inherent in the organization of the parietal cortex. As we saw in the discussion of unilateral neglect in  Chapter 1 , the parietal cortex is involved in our awareness of our own bodies. Indeed, people with lesions of the parietal lobe (especially in the right hemisphere) have been known to push their own leg out of bed, believing that it belongs to someone else. Melzak reports that some people who were born with missing limbs nevertheless experience phantom limb sensations, which would suggest that our brains are genetically programmed to provide sensations for all four limbs.

ENDOGENOUS MODIFICATION OF PAIN SENSITIVITY

For many years, investigators have known that perception of pain can be modified by environmental stimuli. Recent work, beginning in the 1970s, has revealed the existence of neural circuits whose activity can produce analgesia. A variety of environmental stimuli can activate these analgesia-producing circuits. Most of these stimuli cause the release of the endogenous opioids, which were described in  Chapter 4 .

Electrical stimulation of particular locations within the brain can cause analgesia, which can even be profound enough to serve as an anesthetic for surgery in rats (Reynolds,  1969 ). The most effective locations appear to be within the periaqueductal gray matter and in the rostroventral medulla. For example, Mayer and Liebeskind ( 1974 ) reported that electrical stimulation of the periaqueductal gray matter produced analgesia in rats equivalent to that produced by at least 10 milligrams (mg) of morphine per kilogram of body weight, which is a large dose. The technique has even found an application in reducing severe, chronic pain in humans: Fine wires are surgically implanted in parts of the central nervous system and attached to a radio-controlled device that permits the patient to administer electrical stimulation when necessary (Kumar, Wyant, and Nath,  1990 ).

FIGURE 7.31 Opiate-Induced Analgesia

The schematic shows the neural circuit that mediates opiate-induced analgesia, as hypothesized by Basbaum and Fields ( 1978 ).

Analgesic brain stimulation apparently triggers the neural mechanisms that reduce pain, primarily by causing endogenous opioids to be released. Basbaum and Fields ( 1978 ,  1984 ), who summarized their work and that of others, proposed a neural circuit that mediates opiate-induced analgesia. Basically, they proposed the following: Endogenous opioids (released by environmental stimuli or administered as a drug) stimulate opiate receptors on neurons in the periaqueductal gray matter. Because the effect of opiates appears to be inhibitory (Nicoll, Alger, and Jahr,  1980 ), Basbaum and Fields proposed that the neurons that contain opiate receptors are themselves inhibitory interneurons. Thus, the administration of opiates activates the neurons on which these interneurons synapse. (See  Figure 7.31 . )

Neurons in the periaqueductal gray matter send axons to the  nucleus raphe magnus , located in the medulla. The neurons in this nucleus send axons to the dorsal horn of the spinal cord gray matter; destruction of these axons eliminates analgesia induced by an injection of morphine. The inhibitory effects of these neurons apparently involve one or two interneurons in the spinal cord. (Look again at  Figure 7.31 . )

 nucleus raphe magnus A nucleus of the raphe that contains serotonin-secreting neurons that project to the dorsal gray matter of the spinal cord and is involved in analgesia produced by opiates.

Pain sensitivity can be regulated by direct neural connections, as well as by secretion of the endogenous opioids. The periaqueductal gray matter receives inputs from the frontal cortex, amygdala, and hypothalamus (Beitz,  1982 ; Mantyh,  1983 ). These inputs permit learning and emotional reactions to affect an animal’s responsiveness to pain even without the secretion of opioids.

Pain can be reduced, at least in some people, by administering a pharmacologically inert placebo. When some people take a medication that they believe will reduce pain, it triggers the release of endogenous opioids and actually does so. This effect is eliminated if the people are given an injection of naloxone, a drug that blocks opiate receptors (Eippert et al.,  2009 ). Thus, for some people a placebo is not pharmacologically inert—it has a physiological effect. The placebo effect may be mediated through connections of the frontal cortex with the periaqueductal gray matter. A functional-imaging study by Zubieta et al. ( 2005 ) found that placebo-induced analgesia did indeed cause the release of endogenous opiates. They used a PET scanner to detect the presence of μ-opioid neurotransmission in the brains of people who responded to the effects of a placebo. As  Figure 7.32  shows, several regions of the brain, including the anterior cingulate cortex and insular cortex, showed evidence of increased endogenous opioid activity. (See  Figure 7.32 . )

An interesting study by Waber et al. ( 2008 ) found that the efficacy of a placebo was directly related to its perceived value. Volunteers were given a placebo pill that was alleged to reduce pain. Some people were told that the pills normally cost $2.50 each, and others were told that the price had been discounted to 10 cents each. Before and after taking the pill, the subjects received electric shocks to their wrists and rated the intensity of the pain that the shocks produced. As  Figure 7.33  shows, subjects who believed that they had received an expensive pill showed a stronger reduction in pain perception than those who believed they had received an inexpensive one. (See  Figure 7.33 . )

A functional-imaging study by Wager et al. ( 2004 ) supports the suggestion that the prefrontal cortex plays a role in placebo analgesia. They administered painful stimuli (heat or electrical shocks) to the skin with or without the application of an “analgesic” skin cream that was actually an unmedicated placebo. They observed a placebo effect—reports of less intense pain and decreased activity in the primary pain-reactive regions of the brain, including the thalamus, ACC, and insular cortex. They also observed increasedactivity in the prefrontal cortex and the periaqueductal gray matter of the midbrain. Presumably, the expectation of decreased sensitivity to pain caused the increased activity of the prefrontal cortex, and connections of this region with the periaqueductal gray matter activated endogenous mechanisms of analgesia. (See  Figure 7.34 . )

FIGURE 7.32 Effects of a Placebo on μ-Opioid Neurotransmission

The figure shows the brains of people who responded to the effects of analgesic placebo. ACC = anterior cingulate cortex, DLPFC = dorsolateral prefrontal cortex, NAC = nucleus accumbens.

(From Wager, T. D., Rilling, J. K., Smith, E. E., Sokolik, A., Casey, K. L., Davidson, R. J., Kosslyn, S. M., Rose, R. M., and Cohen, J. D. Science, 2004, 303, 1162–1166. Copyright © American Association for the Advancement of Science. Reprinted with permission.)

FIGURE 7.33 Effect of Perceived Price of a Drug on Placebo Analgesia

The graph shows that subjects reported less pain reduction from a placebo when they thought it was priced at a discount.

FIGURE 7.34 The Placebo Effect

Functional MRI scans show increased activity in the dorsolateral prefrontal cortex and the periaqueductal gray matter of the midbrain of subjects who showed decrease sensitivity to pain in response to administration of a placebo.

(From Zubieta, J.-K., Bueller, J. A., Jackson, L. R., Scott, D .J., Xu, Y., Koeppe, R. A., Nichols, T. E., and Stohler, C. S. Journal of Neuroscience, 2005, 25, 7754–7762. Reprinted with permission.)

It appears that a considerable amount of neural circuitry is devoted to reducing the intensity of pain. What functions do these circuits perform? When an animal encounters a noxious stimulus, the animal usually stops what it is doing and engages in withdrawal or escape behaviors. Obviously, these responses are quite appropriate. However, they are sometimes counterproductive. For example, males fighting for access to females during mating season will fail to pass on their genes if pain elicits withdrawal responses that interfere with fighting. In fact, fighting and sexual activity both stimulate brain mechanisms of analgesia.

Komisaruk and Larsson ( 1971 ) found that gentle probing of a rat’s vagina with a glass rod produced analgesia. Such probing also increases the activity of neurons in the periaqueductal gray matter and decreases the responsiveness of neurons in the ventrobasal thalamus to painful stimulation (Komisaruk and Steinman,  1987 ). The phenomenon also occurs in humans; Whipple and Komisaruk ( 1988 ) found that self-administered vaginal stimulation reduces sensitivity to painful stimuli but not to neutral tactile stimuli. Presumably, copulation triggers analgesic mechanisms. The adaptive significance of this phenomenon is clear: Painful stimuli encountered during the course of copulation are less likely to cause the behavior to be interrupted; thus, the chances of pregnancy are increased.

SECTION SUMMARY: Somatosenses

Cutaneous sensory information is provided by specialized receptors in the skin. Glabrous skin is the hairless skin on the palms and soles of the feet. Cutaneous receptors in this skin are involved with touching and exploring items in the environment and in and manipulating objects. Merkel’s disks provide information about form and roughness, especially to the fingertips. Ruffini corpuscles provide information about static forces to the skin and about stretching of the skin, which contributes to kinesthetic feedback. Meissner’s corpuscles provide information about edge contours and to Braille-like stimuli, especially to the fingertips. Pacinian corpuscles provide information about vibration, especially that detected by contact by the ends of elongated objects such as tools with other objects. Painful stimuli and changes in temperature are detected by free nerve endings.

When the dendrites of mechanoreceptors bend, ion channels open, producing a receptor potential. Although most tactile information is transmitted to the CNS via fast-conducting myelinated axons, gentle stroking produces a pleasant sensation mediated by small, unmyelinated axons. This information is received by the insular cortex, a region associated with emotional responses.

Unless the skin is moving, tactile sensation provides little information about the nature of objects we touch. Movement and manipulation provide information about the shape, mass, texture, and other physical characteristics of objects we feel. Tactile experience, such as that gained by musicians, increases the portion of the somatosensory cortex devoted to the fingers involved in this experience.

Temperature receptors adapt to the ambient temperature; moderate changes in skin temperature are soon perceived as neutral, and deviations above or below this temperature are perceived as warmth or coolness. Transduction of different ranges of temperatures is accomplished by six members of the TRP (transient receptor potential) family of receptors. One of the coolness receptors, TRPM8, also responds to menthol and is involved in responsiveness to environmental cold. There are at least three different types of pain receptors: high-threshold mechanoreceptors; fibers with capsaicin receptors (TRPV1 receptors), which detect extremes of heat, acids, and the presence of capsaicin; and fibers with TRPA1 receptors, which are sensitive to chemical irritants and inflammation. Itch is an unpleasant sensation conveyed by two different types of unknown receptors. Pain and itch are mutually inhibitory.

Precise, well-localized somatosensory information is conveyed by a pathway through the dorsal columns and their nuclei and the medial lemniscus, connecting the dorsal column nuclei with the ventral posterior nuclei of the thalamus. Information about pain and temperature ascends the spinal cord through the spinothalamic system. Organic sensibility reaches the central nervous system by means of axons that travel through nerves of the autonomic nervous systems.

The neurons in the primary somatosensory cortex are topographically arranged, according to the part of the body from which they receive sensory information (somatotopic representation). Columns within the somatosensory cortex respond to a particular type of stimulus from a particular region of the body. Different types of somatosensory receptors send their information to separate areas of the somatosensory cortex. Damage to the somatosensory association cortex can cause tactile agnosia, inability to recognize common objects by means of touch. Tactile apraxia refers to difficulty exploring objects with the fingers.

A particular voltage-dependent sodium channel, Nax1.7, plays an essential role in pain sensation. Mutations of the gene for this protein produce total insensitivity to pain. Pain perception is not a simple function of stimulation of pain receptors; it is a complex phenomenon with sensory and emotional components that can be modified by experience and the immediate environment. The sensory component is mediated by the primary and secondary somatosensory cortex, the immediate emotional component appears to be mediated by the anterior cingulate cortex and the insular cortex, and the long-term emotional component appears to be mediated by the prefrontal cortex. Functional-imaging studies using hypnotic suggestion found that a decrease in the sensory component of pain reduced activation of the somatosensory cortex and that reduction of the unpleasantness of pain reduced the activation of the anterior cingulate cortex. The phantom limb phenomenon, which often is accompanied by phantom pain, appears to be inherent in the organization of the parietal lobe.

Just as we have mechanisms to perceive pain, we have mechanisms to reduce it—to produce analgesia. In the appropriate circumstances, neurons in the periaqueductal gray matter are stimulated through synaptic connections with the frontal cortex, amygdala, and hypothalamus. In addition, some neurosecretory cells in the brain release enkephalins, a class of endogenous opioids. Connections from the periaqueductal gray matter to the nucleus raphe magnus of the medulla activate serotonergic neurons located there. These neurons send axons to the dorsal horn of the spinal cord gray matter, where they inhibit the transmission of pain information to the brain. In humans, chronic pain is sometimes treated by implanting electrodes in the periaqueductal gray matter or the thalamus and permitting the patients to stimulate the brain through these electrodes when the pain becomes severe.

Functional-imaging studies suggest that the placebo effect may be caused by increased activity of the prefrontal cortex, which activates the periaqueductal gray matter and inhibits the activity of the anterior cingulate cortex and insular cortex, inducing analgesia. Analgesia occurs when it is important for an animal to continue a behavior that would tend to be inhibited by pain—for example, mating or fighting. The administration of a placebo can also produce analgesia. Because this effect is blocked by naloxone, it must involve the release of endogenous opioids.

■ THOUGHT QUESTION

Our fingertips and our lips are the most sensitive parts of our bodies; relatively large amounts of the primary somatosensory cortex are devoted to analyzing information from these parts of the body. It is easy to understand why fingertips are so sensitive: We use them to explore object by touch. But why are our lips so sensitive? Does it have something to do with eating?

Gustation

The stimuli that we have encountered so far produce receptor potentials by imparting physical energy: thermal, photic (involving light), or kinetic. However, the stimuli received by the last two senses to be studied—gustation and olfaction—interact with their receptors chemically. This section discusses the first of them: gustation.

The Stimuli

Gustation is clearly related to eating; this sense modality helps us to determine the nature of things we put in our mouths. For a substance to be tasted, molecules of it must dissolve in the saliva and stimulate the taste receptors on the tongue. Tastes of different substances vary, though much less than we generally realize. There are only six qualities of taste: bitterness, sourness, sweetness, saltiness, umami, and fat. You are familiar with the first four qualities, and I will describe the fifth and sixth later. Flavor, as opposed to taste, is a composite of olfaction and gustation. Much of the flavor of food depends on its odor; anosmicpeople (who lack the sense of smell) or people whose nostrils are stopped up have difficulty distinguishing between different foods by taste alone.

Most vertebrates possess gustatory systems that respond to all six taste qualities. (An exception is the cat family; lions, tigers, leopards, and house cats do not detect sweetness—but then, none of the food they normally eat is sweet.) Clearly, sweetness receptors are food detectors. Most sweet-tasting foods, such as fruits and some vegetables, are safe to eat (Ramirez,  1990 ). Saltiness receptors detect the presence of sodium chloride. In some environments, inadequate amounts of this mineral are obtained from the usual source of food, so sodium chloride detectors help the animal to detect its presence. Injuries that cause bleeding deplete an organism of its supply of sodium rapidly, so the ability to find it quickly can be critical. In recent years, researchers have recognized the existence of a fifth taste quality: umami.  Umami , a Japanese word that means “good taste,” refers to the taste of monosodium glutamate (MSG), a substance that is often used as a flavor enhancer in Asian cuisine (Kurihara,  1987 ; Scott and Plata-Salaman,  1991 ). The umami receptor detects the presence of glutamate, an amino acid found in proteins. Presumably, the umami receptor provides the ability to taste proteins, an important nutrient.

 umami ( oo mah mee ) The taste sensation produced by glutamate.

Most species of animals will readily ingest substances that taste sweet or somewhat salty. Similarly, they are attracted to foods that are rich in amino acids, which explains the use of MSG as a flavor enhancer. However, they will tend to avoid substances that taste sour or bitter. Because of bacterial activity, many foods become acidic when they spoil. In addition, most unripe fruits are acidic. Acidity tastes sour and causes an avoidance reaction. (Of course, we have learned to make highly preferred mixtures of sweet and sour, such as lemonade.) Bitterness is almost universally avoided and cannot easily be improved by adding some sweetness. Many plants produce poisonous alkaloids, which protect them from being eaten by animals. Alkaloids taste bitter; thus, the bitterness receptor undoubtedly serves to warn animals away from these chemicals.

For many years, researchers have known that many species of animals (including our own) show a distinct preference for high-fat foods. Because there is not a distinct taste that is associated with the presence of fat, most investigators concluded that we detected fat by its odor and texture (“mouth feel”). However, Fukuwatari et al. ( 2003 ) found that rats whose olfactory sense was destroyed continued to show a preference for a liquid diet containing a long-chain fatty acid, one of the breakdown products of fat. When fats reach the tongue, some of these molecules are broken down into fatty acids by an enzyme called lingual lipase, which is found in the vicinity of taste buds. The activity of lingual lipase ensures that fatty acid detectors are stimulated when food containing fat enters the mouth. Cartoni et al. ( 2010 ) identified two G protein-coupled receptors that appear to be responsible for detecting the presence of fatty acids in the mouth. The investigators found that mice with a targeted mutation against the genes responsible for the production of these receptors showed a decreased preference for fatty acids, and that responses of the taste nerves to fatty acids were also diminished.

Anatomy of the Taste Buds and Gustatory Cells

The tongue, palate, pharynx, and larynx contain approximately 10,000 taste buds. Most of these receptive organs are arranged around papillae, small protuberances of the tongue. Fungiform papillae, located on the anterior two-thirds of the tongue, contain up to eight taste buds, along with receptors for pressure, touch, and temperature. Foliate papillae consist of up to eight parallel folds along each edge of the back of the tongue. Approximately 1300 taste buds are located in these folds. Circumvallate papillae, arranged in an inverted V on the posterior third of the tongue, contain approximately 250 taste buds. They are shaped like little plateaus surrounded by moatlike trenches. Taste buds consist of groups of twenty to fifty receptor cells, specialized neurons arranged somewhat like the segments of an orange. Cilia are located at the end of each cell and project through the opening of the taste bud (the pore) into the saliva that coats the tongue. Tight junctions between adjacent taste cells prevent substances in the saliva from diffusing freely into the taste bud itself.  Figure 7.35  shows the appearance of a circumvallate papilla; a cross section through the surrounding trench contains a taste bud. (See  Figure 7.35 . )

FIGURE 7.35 The Tongue

(a) Papillae on the surface of the tongue. (b) Taste buds.

Taste receptor cells form synapses with dendrites of bipolar neurons whose axons convey gustatory information to the brain through the seventh, ninth, and tenth cranial nerves. The neurotransmitter released by the receptor cells is adenosine triphosphate (ATP), the molecule produced by mitochondria that stores energy within cells (Finger et al.,  2005 ). The receptor cells have a life span of only ten days. They quickly wear out, being directly exposed to a rather hostile environment. As they degenerate, they are replaced by newly developed cells; the dendrite of the bipolar neuron is passed on to the new cell (Beidler,  1970 ).

Perception of Gustatory Information

Transduction of taste is similar to the chemical transmission that takes place at synapses: The tasted molecule binds with the receptor and produces changes in membrane permeability that cause receptor potentials. Different substances bind with different types of receptors, producing different taste sensations. In this section I will describe what we know about the nature of the molecules with particular tastes and the receptors that detect their presence.

To taste salty, a substance must ionize. Although the best stimulus for saltiness receptors is sodium chloride (NaCl), a variety of salts containing metallic cations (such as Na+, K+, and Li+) with a small anion (such as Cl–, Br–, SO42–, or NO3–) taste salty. The receptor for saltiness seems to be a simple sodium channel. When present in the saliva, sodium enters the taste cell and depolarizes it, triggering action potentials that cause the cell to release a neurotransmitter (Avenet and Lindemann,  1989 ; Kinnamon and Cummings,  1992 ). The best evidence that sodium channels are involved is the fact that amiloride, a drug that is known to block sodium channels, prevents sodium chloride from activating taste cells and decreases sensations of saltiness. However, the drug does not completely block these sensations in humans, so most investigators believe that more than one type of receptor is involved (Schiffman, Lockhead, and Maes,  1983 ; Ossebaard, Polet, and Smith,  1997 ).

Sourness receptors appear to respond to the hydrogen ions present in acidic solutions. However, because the sourness of a particular acid is not simply a function of the concentration of hydrogen ions, the anions must have an effect as well. The reason for this anion effect is not yet known. Huang et al. ( 2006 ) reported the discovery of the sourness receptor: a transient receptor potential ion channel known as PKD2L1. (The unfortunate name for this channel is polycystic-kidney-disease-like ion channel.)  Figure 7.36  shows activity recorded from nerves that serve the gustatory receptors of the tongues of normal mice and mice with a knockout of the gene for the PKD2L1 ion channel. As you can see, afferent taste fibers of normal mice showed responses to five categories of taste stimuli, but PKD2L1 knockout mice showed no response to the acids. However, the responses of these mice to the other four categories of tastes were normal. (See  Figure 7.36 . )

The stimulus for sourness—the presence of acids—is clear. However, bitter and sweet substances are more difficult to characterize. The typical stimulus for bitterness is a plant alkaloid such as quinine; for sweetness it is a sugar such as glucose or fructose. The fact that some molecules elicit both sensations suggested to early researchers that bitterness and sweetness receptors may be similar. For example, the Seville orange rind contains a glycoside (complex sugar) that tastes extremely bitter; the addition of a hydrogen ion to the molecule makes it taste intensely sweet (Horowitz and Gentili,  1974 ). Some amino acids taste sweet. Indeed, the commercial sweetener aspartame consists of just two amino acids: aspartate and phenylalanine.

Receptors sensitive to bitterness and sweetness are linked to a G protein known as gustducin, which is very similar in structure to transducin, the G protein involved in transduction of photic information in the retina. Receptors sensitive to umami are linked to both gustducin and transducin (McLaughlin et al.,  1993 ; Wong, Gannon, and Margolskee,  1996 ; He et al.,  2004 ). When a bitter molecule binds with the receptor, the G protein activates an enzyme that begins a cycle of chemical reactions that causes the release of ATP, the neurotransmitter of taste receptor cells.

FIGURE 7.36 The Sourness Receptor

Responses were recorded from nerves that serve the gustatory receptors of the tongues of normal mice and mice with a knockout (KO) of the PKD2L1 transient receptor potential ion channel. Only sensitivity to sour-tasting substances is affected by the mutation.

(Adapted from Huang, A. L., Chen, X., Hoon, M.A., Chandrashekar, J., Guo, W., Tränker, D., Ryba, N. J. P., and Zuker, C. S. Nature, 2006, 442, 934–938.)

Recent evidence has discovered two families of receptors responsible for detecting sweet, bitter, and umami tastes (see Scott,  2004 , for a review). The first family, T1R, has three members: T1R1, T1R2, and T1R3, produced by three different genes. The sweet receptor consists of two components: T1R2 + T1R3. The umami receptors consists of T1R1 + T1R3. A given gustatory receptor cell can be sensitive to sweet or umami but not both. Bitter compounds are detected by the second family of receptors, T2R, of which there are 30 members (Matsunami, Montmayeur, and Buck,  2000 ). A given gustatory receptor cell sensitive to bitterness contains one of the many different varieties of T2R, which indicates that each cell can detect the presence of many different bitter-tasting molecules. As we saw, many compounds found in nature that taste bitter to us are poisonous. Rather than entrusting detection of these compounds to a single receptor, the process of evolution has given us the ability to detect a wide variety of compounds with different molecular shapes. (See  Figure 7.37 . )

FIGURE 7.37 Structure of Taste Receptors

This schematic drawing of the structure of receptors responsible for detection of sweet, bitter, and umami tastes.

The T2R bitter receptor is also present in the mucous membrane of the nose, where it detects irritants and bacteria (Tizzano et al.,  2010 ). When they are stimulated, these receptors trigger protective responses such as sneezing. Jeon et al. ( 2008 ) found that T2R bitter receptors in the gut may play a role in decreasing the absorption of toxic substances that have already been ingested.

I mentioned earlier that cats are insensitive to sweet tastes. Li et al. ( 2005 ) discovered the reason for the absence of sweet sensitivity: The DNA of members of the cat family (the investigators tested domestic cats, tigers, and cheetahs) lacks functional genes that produce T1R2 proteins, one of the components of sweet receptors. (Look again at  Figure 7.37 . ) The investigators suggested that this mutation was probably an important event in the evolution of cats’ carnivorous behavior. Margolskee et al. ( 2007 ) found that T1R3 sweet receptors in the gut of mice detect the presence of sugar and artificial sweeteners and are involved in control of glucose absorption. Mice with a targeted mutation against the T1R3 gene were insensitive to the presence of sweet substances in the gut.

The Gustatory Pathway

Gustatory information is transmitted through cranial nerves 7, 9, and 10. Information from the anterior part of the tongue travels through the  chorda tympani , a branch of the seventh cranial nerve (facial nerve). Taste receptors in the posterior part of the tongue send information through the lingual (tongue) branch of the ninth cranial nerve (glossopharyngeal nerve); the tenth cranial nerve (vagus nerve) carries information from receptors of the palate and epiglottis. The chorda tympani gets its name because it passes through the middle ear just beneath the tympanic membrane. Because of its convenient location, it is accessible to a recording or stimulating electrode. Investigators have even recorded from this nerve during the course of human ear operations.

 chorda tympani A branch of the facial nerve that passes beneath the eardrum; conveys taste information from the anterior part of the tongue and controls the secretion of some salivary glands.

The first relay station for taste is the  nucleus of the solitary tract , located in the medulla. In primates the taste-sensitive neurons of this nucleus send their axons to the ventral posteromedial thalamic nucleus, a nucleus that also receives somatosensory information received from the trigeminal nerve (Beckstead, Morse, and Norgren,  1980 ). Thalamic taste-sensitive neurons send their axons to the primary gustatory cortex, which is located in the base of the frontal cortex and in the insular cortex (Pritchard et al.,  1986 ). Neurons in this region project to the secondary gustatory cortex, located in the caudolateral orbitofrontal cortex (Rolls, Yaxley, and Sienkiewicz,  1990 ). Unlike most other sense modalities, taste is ipsilaterally represented in the brain; that is, the right side of the tongue projects to the right side of the brain, and the left side projects to the left. (See  Figure 7.38 . )

 nucleus of the solitary tract A nucleus of the medulla that receives information from visceral organs and from the gustatory system.

FIGURE 7.38 Neural Pathways of the Gustatory System

In a functional-imaging study, Schoenfeld et al. ( 2004 ) had people sip water that was flavored with sweet, sour, bitter, and umami tastes. The investigators found that tasting each flavor activated different regions in the primary gustatory area of the insular cortex. Although the locations of the taste-responsive regions differed from subject to subject, the same pattern was seen when a given subject was tested on different occasions. Thus, the representation of tastes in the gustatory cortex is idiosyncratic but stable. (See  Figure 7.39 . )

FIGURE 7.39 Activation of the Primary Gustatory Cortex by Taste Stimuli

Functional MRI images of the brains of six subjects revealed that the responsive regions varied between subjects but were stable for each subject.

(From Schoenfeld, M. A., Neuer, G., Tempelmann, C., Schüssler, K., Noesselt, T., Hopf, J.-M., and Heinze, H.-J. Neuroscience, 2004, 127, 347–353 with permission from Elsevier.)

Besides receiving information from taste receptors, the gustatory cortex also receives thermal, mechanical, visceral, and nociceptive (painful) stimuli, which undoubtedly play a role in determining the palatability of food (Carleton, Accola, and Simon,  2010 ). Gustatory information also reaches the amygdala and the hypothalamus and adjacent basal fore-brain (Nauta,  1964 ; Russchen, Amaral, and Price,  1986 ). Many investigators believe that the hypothalamic pathway plays a role in mediating the reinforcing effects of sweet, umami, and slightly salty tastes. In fact, some neurons in the hypothalamus respond to sweet stimuli only when the animal is hungry (Rolls et al.,  1986 ).

SECTION SUMMARY: Gustation

Taste receptors detect only six sensory qualities: bitterness, sourness, sweetness, saltiness, umami, and fat. Bitter foods often contain plant alkaloids, many of which are poisonous. Sour foods have usually undergone bacterial fermentation, which can produce toxins. On the other hand, sweet foods (such as fruits) are usually nutritious and safe to eat, and salty foods contain an essential cation: sodium. The fact that people in affluent cultures today tend to ingest excessive amounts of sweet and salty foods suggests that these taste qualities are naturally reinforcing. Umami, the taste of glutamate, identifies proteins.

Saltiness receptors appear to be simple sodium channels. Sourness receptors appear to detect the presence of hydrogen ions, which activate a transient receptor potential ion channel known as PKD2L1. Bitter, sweet, and umami tastes are detected by two families of receptors: sweetness by a receptor consisting of T1R2 + T1R3, umami by one consisting of T1R1 + T1R3, and bitterness by thirty different members of the T2R family. Two G protein-coupled receptors detect molecules of fatty acids produced when an enzyme, lingual lipase, breaks down some molecules of fat in the mouth.

Gustatory information from the anterior part of the tongue travels through the chorda tympani, a branch of the facial nerve that passes beneath the eardrum on its way to the brain. The posterior part of the tongue sends gustatory information through the glossopharyngeal nerve, and the palate and epiglottis send gustatory information through the vagus nerve. Gustatory information is received by the nucleus of the solitary tract (located in the medulla) and is relayed by the ventral posteromedial thalamus to the primary gustatory cortex in the basal frontal and insular areas. Different tastes activate different regions of the primary gustatory cortex. The caudolateral orbitofrontal cortex contains the secondary gustatory cortex. Gustatory information is also sent to the amygdala, hypothalamus, and basal forebrain.

■ THOUGHT QUESTION

Bees and birds can taste sweet substances, but cats and alligators cannot. Obviously, the ability to taste particular substances is related to the range of foods a species eats. If, through the process of evolution, a species develops a greater range of foods, what do you think comes first: the food or the receptor? Would a species start eating something new (say, something with a sweet taste) and later develop the appropriate taste receptors, or would the taste receptors evolve first and then lead the animal to a new taste?

Olfaction

Olfaction, the second chemical sense, helps us to identify food and avoid food that has spoiled and is unfit to eat. It helps the members of many species to track prey or detect predators and to identify friends, foes, and receptive mates. Although many other mammals, such as dogs, have more sensitive olfactory systems than humans do, we should not underrate our own. The olfactory system is second only to the visual system in the number of sensory receptor cells, with an estimated 10 million cells. We can smell some substances at lower concentrations than the most sensitive laboratory instruments can detect.

For years I have told my students that one reason for the difference in sensitivity between our olfactory system and those of other mammals is that other mammals put their noses where odors are the strongest—just above the ground. For example, a dog following an odor trail sniffs along the ground, where the odors of a passing animal may have clung. Even a bloodhound’s nose would not be very useful if it were located five or six feet above the ground, as ours is. I was gratified to learn that a scientific study established the fact that when people sniff the ground as dogs do, their olfactory system works much better. Porter et al. ( 2007 ) prepared a scent trail—a string moistened with essential oil of chocolate and laid down in a grassy field. The subjects were blindfolded and wore earmuffs, knee-pads, and gloves, which prevented them from using anything other than their noses to follow the scent trail. They did quite well, and they adopted the same zigzag strategy used by dogs. (See  Figure 7.40 . ) As the authors wrote, these findings “suggest that the poor reputation of human olfaction may reflect, in part, behavioral demands rather than ultimate abilities” (Porter et al.,  2007 , p. 27).

The Stimulus

The stimulus for odor (known formally as odorants) consists of volatile substances having a molecular weight in the range of approximately 15–300. Almost all odorous compounds are lipid soluble and of organic origin. However, many substances that meet these criteria have no odor at all, so we still have much to learn about the nature of odorants.

Anatomy of the Olfactory Apparatus

Our 6 million olfactory receptor cells reside within two patches of mucous membrane (the  olfactory epithelium ), each having an area of about 1 square inch. The olfactory epithelium is located at the top of the nasal cavity, as shown in  Figure 7.41 .  Less than 10 percent of the air that enters the nostrils reaches the olfactory epithelium; a sniff is needed to sweep air upward into the nasal cavity so that it reaches the olfactory receptors.

 olfactory epithelium The epithelial tissue of the nasal sinus that covers the cribriform plate; contains the cilia of the olfactory receptors.

FIGURE 7.40 Scent-Tracking Behavior

The path followed by a dog and a human during the scent tracking is shown in red.

(From Porter, J., Craven, B., Khan, R. M., Chang, S.-J., Kang, I Judkewitz, B., Volpe, J., Settles, G., and Sobel, N. Nature Neuroscience, 2007, 10, 27–29.)

The inset in  Figure 7.41  illustrates a group of olfactory receptor cells, along with their supporting cells. (See Inset,  Figure 7.41 . ) Olfactory receptor cells are bipolar neurons whose cell bodies lie within the olfactory mucosa that lines the cribriform plate, a bone at the base of the rostral part of the brain. There is a constant production of new olfactory receptor cells, but their life is considerably longer than those of gustatory receptor cells. Supporting cells contain enzymes that destroy odorant molecules and thus help to prevent them from damaging the olfactory receptor cells.

Olfactory receptor cells send a process toward the surface of the mucosa, which divides into ten to twenty cilia that penetrate the layer of mucus. Odorous molecules must dissolve in the mucus and stimulate receptor molecules on the olfactory cilia. Approximately thirty-five bundles of axons, ensheathed by glial cells, enter the skull through small holes in the cribriform (“perforated”) plate. The olfactory mucosa also contains free nerve endings of trigeminal nerve axons; these nerve endings presumably mediate sensations of pain that can be produced by sniffing some irritating chemicals, such as ammonia.

The  olfactory bulbs  lie at the base of the brain on the ends of the stalklike olfactory tracts. Each olfactory receptor cell sends a single axon into an olfactory bulb, where it forms synapses with dendrites of  mitral cells  (named for their resemblance to a bishop’s miter, or ceremonial headgear). These synapses take place in the complex axonal and dendritic arborizations called  olfactory glomeruli  (from glomus, “ball”). There are approximately 10,000 glomeruli, each of which receives input from a bundle of approximately 2000 axons. The axons of the mitral cells travel to the rest of the brain through the olfactory tracts. Some of these axons terminate in other regions of the ipsilateral forebrain; others cross the brain and terminate in the contralateral olfactory bulb.

 olfactory bulb The protrusion at the end of the olfactory tract; receives input from the olfactory receptors.

 mitral cell A neuron located in the olfactory bulb that receives information from olfactory receptors; axons of mitral cells bring information to the rest of the brain.

 olfactory glomerulus ( glow  mare  you luss ) A bundle of dendrites of mitral cells and the associated terminal buttons of the axons of olfactory receptors.

Olfactory tract axons project directly to the amygdala and to two regions of the limbic cortex: the piriform cortex (the primary olfactory cortex) and the entorhinal cortex. (Look again at  Figure 7.41 . ) The amygdala sends olfactory information to the hypothalamus, the entorhinal cortex sends it to the hippocampus, and the piriform cortex sends it to the hypothalamus and to the orbitofrontal cortex via the dorsomedial nucleus of the thalamus (Buck,  1996 ; Shipley and Ennis,  1996 ). As you may recall, the orbitofrontal cortex also receives gustatory information; thus, it may be involved in the combining of taste and olfaction into flavor. The hypothalamus also receives a considerable amount of olfactory information, which is probably important for the acceptance or rejection of food and for the olfactory control of reproductive processes seen in many species of mammals.

Most mammals have another organ that responds to chemicals in the environment: the vomeronasal organ. Because it plays an important role in animals’ responses to pheromones, chemicals produced by other animals that affect reproductive physiology and behavior, its structure and function are described in  Chapter 10 .

Efferent fibers from several locations in the brain enter the olfactory bulbs. These include acetylcholinergic, noradrenergic, dopaminergic, and serotonergic inputs (Shipley and Ennis,  1996 ).

FIGURE 7.41 The Olfactory System

Transduction of Olfactory Information

For many years, researchers have recognized that olfactory cilia contain receptors that are stimulated by molecules of odorants, but the nature of the receptors was unknown. Jones and Reed ( 1989 ) identified a particular G protein, which they called Golf. This protein is able to activate an enzyme that catalyzes the synthesis of cyclic AMP, which, in turn, can open sodium channels and depolarize the membrane of the olfactory cell (Nakamura and Gold,  1987 ; Firestein, Zufall, and Shepherd,  1991 ; Menco et al.,  1992 ).

As we saw in  Chapter 2 , G proteins serve as the link between metabotropic receptors and ion channels: When a ligand binds with a metabotropic receptor, the G protein either opens ion channels directly or does so indirectly, by triggering the production of a second messenger. The discovery of Golf suggested that olfactory cilia contained odorant receptors linked to this G protein. Indeed, Buck and Axel ( 1991 ) used molecular genetics techniques and discovered a family of genes that code for a family of olfactory receptor proteins (and in 2004 won a Nobel Prize for doing so). So far, olfactory receptor genes have been isolated in more than twelve species of vertebrates, including mammals, birds, and amphibians (Mombaerts,  1999 ). Humans have 339 different olfactory receptor genes, and mice have 913 (Godfrey, Malnic, and Buck,  2004 ; Malnic, Godfrey, and Buck,  2004 ). Molecules of odorant bind with olfactory receptors, and the G proteins coupled to these receptors open sodium channels and produce depolarizing receptor potentials.

Perception of Specific Odors

For many years, recognition of specific odors has been an enigma. Humans can recognize up to 10,000 different odorants, and other animals can probably recognize even more (Shepherd,  1994 ). Even with 339 different olfactory receptors, that leaves many odors unaccounted for. And every year, chemists synthesize new chemicals, many with odors unlike those that anyone has previously detected. How can we use a relatively small number of receptors to detect so many different odorants?

FIGURE 7.42 Connections of Olfactory Receptor Cells with Glomeruli

Each glomerulus of the olfactory bulb receives information from only one type of receptor cell. Olfactory receptor cells of different colors contain different types of receptor molecules.

Before I answer this question, we should look more closely at the relationship between receptors, olfactory neurons, and the glomeruli to which the axons of these neurons project. First, the cilia of each olfactory neuron contain only one type of receptor (Nef et al.,  1992 ; Vassar, Ngai, and Axel,  1993 ). As we saw, each glomerulus receives information from approximately two thousand olfactory receptor cells. Ressler, Sullivan, and Buck ( 1994 ) discovered that each of these 2000 cells contains the same type of receptor molecule. Thus, there are as many types of glomeruli as there are types of receptor molecules. Furthermore, the location of particular types of glomeruli (defined by the type of receptor that sends information to them) appears to be the same in each of the olfactory bulbs in a given animal and may even be the same from one animal to another. (See  Figure 7.42 . )

An ingenious study by Zou et al. ( 2001 ) investigated the specificity of olfactory information in the pathway from olfactory receptors to olfactory glomeruli to the olfactory cortex. To accomplish this feat, they inserted a gene for a transneuronal tracer protein (barley lectin) into the DNA of mice adjacent to two different olfactory receptor genes. Because of the location of this gene, it was turned on only in olfactory receptor cells that produced one of the two selected receptor genes. Thus, two different types of olfactory receptor cells expressed barley lectin. This protein is transmitted from one neuron to others, with which it forms synapses. Thus, it was carried to glomeruli and from there to a third set of neurons in the olfactory cortex. The investigators found that, just as retinotopic information is maintained in the visual system and tonotopic information is maintained in the auditory system, “olfactotopic” information is maintained in the olfactory system. That is, the particular glomeruli that receive information from particular olfactory receptors send this information to specific regions of olfactory cortex. These regions appeared to occur in identical locations in different mice.

Now let’s get back to the question I just posed: How can we use a relatively small number of receptors to detect so many different odorants? The answer is that a particular odorant binds to more than one receptor. Thus, because a given glomerulus receives information from only one type of receptor, different odorants produce different patterns of activity in different glomeruli. Recognizing a particular odor, then, is a matter of recognizing a particular pattern of activity in the glomeruli. The task of chemical recognition is transformed into a task of spatial recognition.

Figure 7.43  illustrates this process (Malnic et al.,  1999 ). The left side of the figure shows the shapes of eight hypothetical odorants. The right side shows four hypothetical odorant receptor molecules. If a portion of the odorant molecule fits the binding site of the receptor molecule, it will activate it and stimulate the olfactory neuron. As you can see, each odorant molecule fits the binding site of at least one of the receptors and in most cases fits more than one of them. Notice also that the pattern of receptors activated by each of the eight odorants is different, which means that if we know which pattern of receptors is activated, we know which odorant is present. Of course, even though a particular odorant might bind with several different types of receptor molecules, it might not bind equally well with each of them. For example, it might bind very well with one receptor molecule, moderately well with another, weakly with another, and so on. (See  Figure 7.43 . ) As we just saw, the spatial pattern of “olfactotopic” information is maintained in the olfactory cortex. Presumably, the olfactory cortex recognizes particular odors by recognizing different patterns of activation there.

Evidence that supports this model was obtained by Johnson, Leon, and their colleagues (Johnson and Leon,  2007 ). The investigators presented a variety of odorants to rats and recorded the regions of activation on the surface of an exposed olfactory bulb. They found that different categories of molecules activated different regions of the olfactory bulb.  Figure 7.44  shows the patterns of activity. Thus, particular characteristics of odorant molecules are represented by particular patterns of activity in the olfactory bulbs. (See  Figure 7.44 . )

FIGURE 7.43 Coding of Olfactory Information

A hypothetical explanation of the coding suggests that different odorant molecules attach to different combinations of receptor molecules. (Activated receptor molecules are shown in blue.) Unique patterns of activation represent particular odorants.

(Adapted from Malnic, B., Hirono, J., Sato, T., and Buck, L. B. Cell, 1999, 96, 713–723.)

Although odorants are categorized according to their molecular characteristics within the olfactory bulb, the coding scheme changes at the level of the piriform cortex (the primary olfactory cortex). A functional-imaging study with humans by Gottfried, Winston, and Dolan ( 2006 ) found that groups of neurons in the anterior region represent the chemical structures of odorants, just as neurons in the olfactory bulb do, but groups of neurons in the posterior region represent the qualities of odorants. Another functional imaging study (Howard et al.,  2009 ) found that odorants normally associated with particular objects (in this case, odorants that people perceive as minty, woody, or citrusy) produced particular patterns of activity in the posterior piriform cortex, regardless of the chemical structure of the odorants. The investigators presented the subjects with three different minty odorants, three different woody odorants, and three different citrusy odorants. Each of the three odorants in each of these categories had very different chemical structures. Nevertheless, the patterns of activity on the posterior piriform cortex were correlated with the odor category, not the molecular structure.  Figure 7.45  shows the molecular structure of the three minty odorants. As you can see, they show little resemblance to each other. (See  Figure 7.45 . )

FIGURE 7.44 Clusters and Zones in the Olfactory Bulb

Specific regions of the olfactory bulb respond to specific features or properties of odorant molecules.

(Adapted from Johnson, B. A., and Leon, M. Journal of Comparative Neurology, 2007, 503, 1–34.)

We do not yet know how maps of chemical structure in the olfactory bulb are combined to form maps of perceptual quality in the posterior piriform cortex. Presumably, learning plays some role in this process.

FIGURE 7.45 Minty-Smelling Molecules

The molecular structures of these molecules are different, but they have similar odors and smelling them produces similar patterns of activity on the posterior piriform cortex.

(Adapted from Howard, J. D., Plailly, J., Grueschow, M., et al. Nature Neuroscience, 2009, 12, 932–938.)

Several studies have found that interactions can take place between glomeruli within the olfactory bulb. For example, some odors have the ability to mask others. (The existence of the deodorant and air-freshener industries depends on this fact.) Cooks in various cultures have long known that as long as it is not too strong, the unpleasant, rancid off-flavor of spoiled food can be masked by the spices fennel and clove. Takahashi, Nagayama, and Mori ( 2004 ) found that evidence for this masking can be seen in the responses of olfactory glomeruli. The investigators used a dental drill to thin the skull of anesthetized rats above an olfactory bulb and moistened it with mineral oil so that it became transparent. Examination of the olfactory bulbs with a microscope showed local areas of increased blood flow when different odorants were presented, which indicated regions of increased neural activity. Takahashi and his colleagues mapped the regions of the olfactory bulb that responded to bad-smelling odorants (alkylamines and aliphatic aldehydes) and to the odors of fennel and clove. They found that responses to the bad odors was suppressed by the presence of the spice odors, indicating that the masking took place in the olfactory bulbs. Presumably, the glomeruli that responded to the spice odors inhibited those that responded to the rancid ones.

SECTION SUMMARY: Olfaction

The olfactory receptors consist of bipolar neurons located in the olfactory epithelium that lines the roof of the nasal sinuses, on the bone that underlies the frontal lobes. The receptors send processes toward the surface of the mucosa, which divide into cilia. The membranes of these cilia contain receptors that detect aromatic molecules dissolved in the air that sweeps past the olfactory mucosa. The axons of the olfactory receptors pass through the perforations of the cribriform plate into the olfactory bulbs, where they form synapses in the glomeruli with the dendrites of the mitral cells. These neurons send axons through the olfactory tracts to the brain, principally to the amygdala, the piriform cortex, and the entorhinal cortex. The hippocampus, hypothalamus, and orbitofrontal cortex receive olfactory information indirectly.

Aromatic molecules produce membrane potentials by interacting with a newly discovered family of receptor molecules, which appears to contain 339 members. These receptor molecules are coupled to a special G protein, Golf. When an odorant molecule bind with and stimulates one of these receptors, Golfcatalyzes the synthesis of cyclic AMP, which opens sodium channels and depolarizes the membrane. Each glomerulus receives information from only one type of olfactory receptor, and “olfactotopic” coding is maintained all the way to the olfactory cortex. This means that the task of detecting different odors is a spatial one; the brain recognizes odors by means of the patterns of activity created in the olfactory cortex. The olfactory bulb encodes information according to the structure of the odorant molecules, and the posterior piriform cortex codes the information it receives from the anterior region according to the odorants’ perceptual categories—for example, minty, woody, and citrusy.

■ THOUGHT QUESTION

Have you ever encountered an odor that you knew was somehow familiar, but you couldn’t say exactly why? Can you think of any explanations? Might this phenomenon have something to do with the fact that the sense of olfaction developed very early in our evolutionary history?

Review Questions

 Study and Review on MyPsychLab

1.

Describe the parts of the ear and the auditory pathway.

2.

Describe the detection of pitch, loudness, and timbre.

3.

Discuss the perception of spatial location, the perception of complex sounds, and the perception of music.

4.

Describe the structures and functions of the vestibular system.

5.

Describe the cutaneous receptors and their response to touch, temperature, and pain.

6.

Describe the somatosensory pathways and the perception of pain.

7.

Describe the five taste qualities, the anatomy of the taste buds and how they detect taste, and the gustatory pathway and neural coding of taste.

8.

Describe the major structures of the olfactory system, explain how odors may be detected, and describe the patterns of neural activity produced by these stimuli.

Explore the Virtual Brain in MyPsychLab

■ MECHANISMS OF PERCEPTION

Each sensory system has its own receptors and neural circuitry. Sensations are only perceived after sensory information reaches the cortex. Association cortex receives sensory information from more than one sense. The Mechanisms of Perception module shows the brain regions involved in the perception of sensory stimuli as well as the brain regions involved in linking sensory stimuli for different senses.