Sensory Transduction

Sensory receptors convert environmental energy into neural signals

Sensation is a cognitive process that requires the full powers of the central nervous system (CNS). Sensation begins with the sensory receptors that actually interface with the world, and these receptors use energy from the environment to trigger electrochemical signals that can be transmitted to the brain—a process called sensory transduction. An understanding of transduction processes is crucial for several reasons. Without these processes, sensation fails. Moreover, a variety of diseases that specifically affect sensory receptors can impair or abolish sensation without damaging the brain. Transduction also sets the basic limits of perception. It determines the sensitivity, range, speed, versatility, and vigor of a sensory system.

We have a variety of senses, each tuned to particular types of environmental energy. These sensory modalities include the familiar ones of seeing, hearing, touching, smelling, and tasting, as well as our senses of pain, balance, body position, and movement. In addition, other intricate sensory systems of which we are not conscious monitor the internal milieu and report on the body's chemical and metabolic state. Early in the 19th century, the physiologist Johannes Müller recognized that neurons that are specialized to evaluate a particular type of stimulus energy will produce the appropriate sensation regardless of how they are activated. For example, banging your eye can produce perceptions of light even in the dark, and seizure activity in a region of the cortex devoted to olfaction can evoke repulsive smells even in a rose garden. This property has been called univariance; in other words, the sensory receptor and its subsequent neural circuits do not know what stimulated them—they give the same type of response regardless. Specificity for each modality is ensured by the structure and position of the sensory receptor.

Sensory transduction uses adaptations of common molecular signaling mechanisms

Evolution is a conservative enterprise. Good ideas are retained, and with slight modification they are adapted to new purposes. Sensory transduction is a prime example of this principle. The sensory processes that are now understood at the molecular level use systems that are closely related to the ubiquitous signaling molecules in eukaryotic cells. Some modalities (vision, olfaction, some types of taste, and other chemoreception) begin with integral membrane proteins that belong to the superfamily of G protein–coupled receptors (GPCRs; see pp. 51–52 ). The second-messenger pathways use the same substances that are used for so many nonsensory tasks in cells, such as cyclic nucleotides, inositol phosphates, and kinases. Other sensory systems (mechanoreceptors, including the hair cells of audition and the vestibular organs, as well as some taste cells) use modified membrane ion channels in the primary transduction process. Although the structures of most of these channels have not yet been determined, their biophysical properties are generally unremarkable, and they are likely to be related to other, nonsensory ion channels. Indeed, the gating of many ion channels from “nonsensory” cells is sensitive to the physical distortion of the membrane that they lie in, which implies that mechanosensitivity is a widespread (although perhaps epiphenomenal) feature of integral membrane proteins.

To achieve a specificity for certain stimulus energies, many sensory receptors must use specialized cellular structures. These, too, are usually adapted from familiar components. Various receptors are slightly modified epithelial cells. Some situate their transduction sites on modified cilia, whereas others use muscle cells or collagen fibers to channel the appropriate forces to the sensory axon. Many are neurons alone, often just bare axons with no specialization visible by microscopy. Most sensory transduction cells (e.g., oxygen and taste sensors, but not olfactory receptors) lack their own axon to communicate with the CNS. For these cells, the communication system of choice is a relatively standard, Ca ²⁺ -dependent system of synaptic transmission onto a primary sensory neuron.

Sensory transduction requires detection and amplification, usually followed by a local receptor potential

Functionally, sensory transducers follow certain general steps. Obviously, they must detect stimulus energy, but they must do so with enough selectivity and speed that stimuli of different types, from different locations, or with different timing are not confused. In most cases, transduction also involves one or more steps of signal amplification so that the sensory cell can reliably communicate the detection of small stimuli (e.g., a few stray photons or a smattering of drifting molecules) to a large brain in an environment with much sensory noise. The sensory cell must then convert the amplified signal into an electrical change by altering the gating of some ion channel. This channel gating leads to alterations of the membrane potential ( V _m ) in the receptor cell—otherwise known as a receptor potential. The receptor potential is not an action potential but a graded electrotonic event that can either modulate the activity of other channels (e.g., voltage-gated Na ⁺ or Ca ²⁺ channels) or trigger action potentials in a different portion of the same cell. Very often, the receptor potential regulates the flux of Ca ²⁺ into the cell and thus controls the release of some synaptic transmitter molecule onto the sensory afferent neuron.

Ultimately, receptor potentials determine the rate and pattern of action potential firing in a sensory neuron. This firing pattern is the signal that is actually communicated to the CNS. Useful information may be encoded in many features of the firing, including its rate, its temporal patterns, its periodicity, its consistency, and its patterns when compared with the signals of other sensory neurons of the same or even different modalities.

Chemoreceptors are ubiquitous, diverse, and evolutionarily ancient

Every cell is bathed in chemicals. Molecules can be food or poison, or they may serve as signals of communication between cells, organs, or individuals. The ability to recognize and respond to environmental chemicals can allow cells to find nutrients, avoid harm, attract a mate, navigate, or regulate a physiological process. Chemoreception has basic and universal advantages. It is the oldest form of sensory transduction, and it exists in many forms. Chemoreception does not even require a nervous system. Single-celled organisms such as bacteria can recognize and respond to substances in their environment. In the broadest sense, every cell in the human body is chemosensitive, and chemical signaling between cells is the basis for internal communication through endocrine systems and neurotransmission. In this chapter, we restrict ourselves to chemoreception as a sensory system, the interface between the nervous system and the external and internal chemical milieu.

Chemicals reach the human body by oral or nasal ingestion, contact with the skin, or inhalation, and once there, they diffuse or are carried to the surface membranes of receptor cells through the various aqueous fluids of the body (e.g., mucus, saliva, tears, cerebrospinal fluid [CSF], blood plasma). The nervous system constantly monitors these chemical comings and goings with a diverse array of chemosensory receptors. The most familiar of these receptors are the sensory organs of taste (gustation) and smell (olfaction). However, chemoreception is widespread throughout the body. Chemoreceptors in the skin, mucous membranes, respiratory tract, and gut warn against irritating substances, and chemoreceptors in the carotid bodies (see pp. 710–712 ) measure blood levels of O ₂ , CO ₂ , and [H ⁺ ].

Taste receptors are modified epithelial cells, whereas olfactory receptors are neurons

The tasks of gustatory and olfactory receptors appear similar at first glance. Both recognize the concentration and identity of dissolved molecules, and they communicate this information to the CNS. In fact, the two systems operate in parallel during eating, and the flavors of most foods are strongly dependent on both taste and smell. The anatomy of the human olfactory system is well adapted to detect odors orthonasally, from the environment, and retronasally, from volatile chemicals released as we chew food. However, the receptor cells of gustation and olfaction are quite different. Olfactory receptors are neurons. Each olfactory cell has small dendrites at one end that are specialized to identify chemical stimuli, and at the other end an axon projects directly into the brain. Taste receptor cells are not neurons but rather modified epithelial cells that synapse onto the axons of sensory neurons that communicate with the CNS.

Taste Receptor Cells

Taste receptors are located mainly on the dorsal surface of the tongue ( Fig. 15-1 A ), concentrated within small but visible projections called papillae (see Fig. 15-1 B ). Papillae are shaped like ridges, pimples, or mushrooms, and each is a few millimeters in diameter. Each papilla in turn has numerous taste buds (see Fig. 15-1 C ). One taste bud contains 50 to 150 taste receptor cells, numerous basal and supporting cells that surround the taste cells, plus a set of sensory afferent axons. Most people have 2000 to 5000 taste buds, although exceptional cases range from 500 to 20,000.

The chemically sensitive part of a taste receptor cell is a small apical membrane region near the surface of the tongue. The apical ends have thin extensions called microvilli that project into the taste pore, a small opening on the surface of the tongue where the taste cells are exposed to the contents of the mouth. Taste cells form synapses with the primary sensory axons near the bottom of the taste bud. However, processing may be more complicated than a simple receptor-to-axon relay. Receptor cells also make both electrical and chemical synapses onto some of the basal cells, some basal cells synapse onto the sensory axons, and some type of information-processing circuit may be present within each taste bud itself.

Cells of the taste bud undergo a constant cycle of growth, death, and regeneration. Each taste cell lives about 2 weeks. The turnover of taste cells depends on the influence of the sensory nerve because if the nerve is cut, taste buds degenerate.

Olfactory Receptor Cells

We smell with receptor cells in the thin main olfactory epithelium, which is placed high in the nasal cavity ( Fig. 15-2 A ). We will not discuss several other accessory olfactory systems, including the vomeronasal organ, which primarily detect pheromones. The main olfactory epithelium has three primary cell types: olfactory receptor cells are the site of transduction; support cells are similar to glia and, among other things, help produce mucus; and stem cells, called basal cells, are the source of new receptor cells (see Fig. 15-2 B ). Olfactory receptors (similar to taste receptors) continually die, regenerate, and grow in a cycle that lasts ~4 to 8 weeks. Olfactory receptor cells are one of the very few types of neurons in the mammalian nervous system that are regularly replaced throughout life.

As we breathe or sniff, chemical odorants waft through the many folds of the nasal passages. However, to contact the receptor cells, odorants must first dissolve in and diffuse through a thin mucous layer, which has both a viscous and a watery portion. The normal olfactory epithelium exudes a mucous layer 20 to 50 µm thick. Mucus flows constantly and is normally replaced about every 10 minutes. Mucus is a complex, water-based substance containing dissolved glycosaminoglycans (see p. 39 ); a variety of proteins, including antibodies, odorant-binding proteins, and enzymes; and various salts. The antibodies are critical because olfactory cells offer a direct route for viruses (e.g., rabies) or bacteria to enter the brain. Odorant-binding proteins in the mucus probably facilitate the diffusion of odorants toward and away from the receptors. Enzymes may help clear the mucus of odorants and thus speed recovery of the receptors from transient odors.

Both the absolute size and the receptor density of the olfactory epithelium vary greatly among species, and they help determine olfactory acuity. The surface area of the human olfactory epithelium is only ~10 cm ² , but this limited area is enough to detect some odorants at concentrations as low as a few parts per trillion. The olfactory epithelia of some dogs may be over 170 cm ² , and dogs have >100 times as many receptors in each square centimeter as humans do. The olfactory acuity of some breeds of dog is legendary and far surpasses that of humans. Dogs can often detect the scent of someone who walked by hours before.

Complex flavors are derived from a few basic types of taste receptors, with contributions from sensory receptors of smell, temperature, texture, and pain

Studies of taste discrimination in humans imply that we can distinguish among 4000 to 10,000 different chemicals with our taste buds. However, behavioral evidence suggests that these discriminations represent only five primary taste qualities: bitter, salty, sweet, and sour plus a primary quality called umami (“delicious” in Japanese). Umami is the taste of certain l -amino acids, epitomized by l -glutamate (monosodium glutamate [MSG], the familiar culinary form). Growing evidence suggests that mammals have a taste system for free fatty acids. Unlike an olfactory receptor cell, which apparently expresses only one receptor type (see p. 358 ), a taste receptor cell may express several.

In many cases, there is an obvious correlation between the chemistry of tastants (i.e., chemicals being tasted) and the quality of their taste. Most acids taste sour and most salts taste salty. However, for many other tastants, the linkage between taste and chemical structure is not clear. The familiar sugars (e.g., sucrose and fructose) are satisfyingly sweet, but certain proteins (e.g., monellin) and artificial sweeteners (e.g., saccharin and aspartame, the latter of which is made from two amino acids: l -aspartyl- l -phenylalanine methyl ester) are 10,000 to 100,000 times sweeter by weight than these sugars. Bitter substances are also chemically diverse. They include simple ions such as K ⁺ (KCl actually simultaneously evokes both bitter and salty tastes), larger metal ions such as Mg ²⁺ , and complex organic molecules such as quinine.

If the tongue has only four or five primary taste qualities available to it, how does it discriminate among the myriad complex flavors that embellish our lives? First, the tongue's response to each tastant reflects distinct proportions of each of the primary taste qualities. In this sense, the taste cells are similar to the photoreceptors of our eyes; with only three different types of color-selective photoreceptive cone cells, we can distinguish a huge palette of colors. Second, the flavor of a tastant is determined not only by its taste but also by its smell. Taste and smell operate in parallel, with information converging in the CNS to aid the important discrimination of foods and poisons. For example, without the aid of olfaction, an onion tastes much like an apple—and both are quite bland. Third, the mouth is filled with other types of sensory receptors that are sensitive to texture, temperature, and pain, and these modalities enhance both the identification and enjoyment of foods. A striking example is the experience of spicy food, which is enjoyable to some but painful to others. The spiciness of hot peppers is generated by the chemical capsaicin, not because of its activation of taste receptor cells but because of its stimulation of heat-sensitive pain receptors in the mouth.

Taste transduction involves many types of molecular signaling systems

The chemicals that we taste have diverse structures, and taste receptors have evolved a variety of mechanisms for transduction. The taste system has adapted many types of membrane-signaling systems to its purposes. Tastants may pass directly through ion channels (salty and sour), bind to and block ion channels (sour) or bind to membrane receptors that activate second-messenger systems, which in turn open or close ion channels (sweet, bitter, and umami). Taste cells use specialized variations of these processes to initiate meaningful signals to the brain.

The receptor potentials of taste cells are usually depolarizing. At least some taste receptor cells can fire action potentials similar to those of neurons, but if the membrane is sufficiently depolarized by whatever means, voltage-gated Ca ²⁺ channels open, and Ca ²⁺ enters the cytoplasm and triggers the release of transmitter molecules. Both the type of neurotransmitter and its mechanism of its release differ by cell type. Sour and salty taste cells use a conventional Ca ²⁺ -triggered vesicular mechanism to release serotonin onto gustatory axons, whereas sweet-, bitter-, and umami-selective taste cells use a Ca ²⁺ -triggered nonvesicular mechanism to release ATP as their transmitter.

Evidence from mice suggests that each taste receptor cell responds to only one of the five basic taste modalities. Each of the taste receptor cells is, in turn, hard-wired to the CNS to convey a particular taste quality. For example, if we genetically alter a mouse to express a bitter receptor in sweet taste receptor cells, the mouse—naturally attracted to sweet tastants—will be attracted to bitter tastants, which now will taste sweet.

The complex diversities of taste transduction are not yet fully understood. The following is a summary of the best-understood transduction processes for the five primary taste qualities in mammals ( Fig. 15-3 ).