Which sense has the most direct route from the sense organ to the brain since its information is not relayed through the thalamus?

Gustatory System

Fig. 12.211. Tongue with epiglottis and gustatory (taste) system. [L127]

Approximately 2,000taste buds (Caliculi gustatorii) can be found on the human tongue (in thePapillae vallatae, fungiformes and foliatae), the soft palate and the epiglottis. Each taste bud consists of different cell types. The actual receptor cells are epithelial cells, which perceive the five primary taste categories (→Fig. 8.167) – sweet, sour, salty, bitter, umami – (the sixth could possibly also be oily). The sensory cells of taste form synapses with axonal plexuses located on the basal side of the taste buds. These are sometimes referred to assecondary sensory cells, since the sensory cells do not depolarise, but their action potential arises only at the synapse with the first afferent neuron. Corresponding to their location, the information is transmitted to theNucleus tractus solitarii in the Medulla oblongata:

from the anterior two-thirds of the tongue via the N. facialis [VII] (Pars intermedia)

from the posterior third of the tongue and the soft palate via the N.glossopharyngeus [IX]

from the epiglottis and the soft palate via the N. vagus [X]

Corresponding to the respective nerves, the perikarya of the first neuron are located in theGanglion geniculi [VII], in theGanglion inferius [IX] (Ganglion petrosum) or in theGanglion inferius [X] (Ganglion nodosum).

In thePars gustatoria (Nucleus gustatorius) of the brain stem, the fibres are relayed onto the second neuron. The axons of the second neuron pass within the ipsilateralTractus tegmentalis centralis (accompanying the Lemniscus medialis) to theNucleus ventralis posteromedialis of the thalamus, where they are switched onto the third neuron. As thalamocortical fibres, they pass to the strictly somatotopically arranged (corresponding to the position of the homunculus) inferior parts of the Gyrus postcentralis, as well as toanterior regions of the insular cortex of the temporal lobe and the Operculum of the frontal lobe. These are the areas of conscious taste perception. Some axons pass directly from the thalamus or indirectly from the Nucleus tractus solitarii via theNucleus parabrachialis medialis to the Hypothalamus and the Amygdala (which influences on autonomic body functions such as appetite, saturation, link with emotions).

Clinical Remarks

Since the excitation threshold for the action potential of taste receptors increases with age, the perception of taste sensations is age-dependent. Deficiency or complete loss of the taste sense is referred to ashypogeusia orageusia, respectively. A common secondary cortical area of the gustatory and olfactory pathways in the orbital-frontal cortex shows the close functional relationship of taste and smell.

3.5 ChR2 transgenic animals in gustatory system

The gustatory system is responsible for detecting the different tastes such as sweet, bitter, salty and sour. Several ChR2 transgenic Drosophila lines have been reported. For example, Zhang et al. targeted ChR2 to Gr5a (gustatory receptor 5a) neurons which have been suggested “sweet” neurons in Drosophila using Gal4-UAS system. They demonstrated that blue light induced proboscis extension in the flies where ChR2 was expressed in Gr5a neurons but not wild-type (WT) flies [83]. So far, no ChR2 transgenic mammalian animals are reported.

Central Gustatory Pathways and Function

Afferent gustatory fibers in the facial, glossopharyngeal, and vagus nerves synapse in the NST of the medulla with a rostral-to-caudal organization.224,225 In primates, taste information projects directly to the gustatory thalamus, situated medial to the oral somatosensory representation in the ventroposteromedial nucleus.226 From the thalamus, taste information projects to the insular-opercular region of the cortex,227 which comprises the primary gustatory cortex, and then to a secondary gustatory cortical area located immediately anterior in the caudolateral orbitofrontal cortex.228 The secondary gustatory cortex projects to several regions of the ventral forebrain, including the hypothalamus and amygdala.16 Positron emission tomography and functional magnetic resonance imaging studies in humans have demonstrated that cortical regions analogous to those demonstrated on the basis of anatomic and physiologic studies in nonhuman primates most likely also comprise the primary and secondary gustatory cortical areas in people (Fig. 86.9).229

The gustatory pathway in rodents is organized somewhat differently. Taste information from the NST reaches an analogous thalamic relay in the ventroposteromedial nucleus, but only after an additional synapse in the parabrachial nucleus of the pons.230,231 The region identified as the primary gustatory cortex in rodents is also the insular cortex,232,233 but a secondary taste cortex has not yet been identified. Instead, taste information reaches limbic areas in rodents more directly via a projection from the parabrachial nucleus.234 However, regardless of species and the route the information takes, it has been hypothesized that the thalamocortical pathway can be specialized for perceptual/discriminative gustatory functions; the limbic projections may be more involved in the hedonic/motivational attributes of taste.235 Local brainstem gustatory pathways, however, have the capacity to mediate basic gustatory discriminative functions. Decerebrate animals236 and anencephalic human infants196 discriminate palatable from unpalatable gustatory stimuli.

Gustatory pathways are in close anatomic proximity with central pathways that control the autonomic nervous system function. This proximity provides a substrate for interactions between gustatory and autonomic afferent information,237 as do the numerous connections between limbic structures and the nuclei in the taste pathway.143 In rodents, an early study demonstrated changes in the firing pattern of gustatory-responsive neurons in the NST in response to gut distention that were indicative of interaction between the autonomic and gustatory systems.238 More recent studies have extended these findings to the parabrachial nucleus. Indeed, not only does gut distention affect parabrachial taste neurons,239 but another manipulation that mimics satiety, intraduodenal lipid infusion, also affects gustatory firing rates.240 Specifically, lipid infusions depress taste responses, and furthermore this occurs mainly for responses to normally preferred gustatory stimuli. Thus lipid infusions most profoundly depress responses in neurons preferentially responsive to NaCl and especially those responsive to sucrose. This is in contrast to a lack of effect on responses evoked by hydrogen chloride (HCl) and QHCl, stimuli that animals do not normally voluntarily ingest.240 These effects of gastric and duodenal stimuli suggest a simple mechanism for the reduction in intake that occurs with the visceral sequelae of intake—namely, that neurons responsive to preferred taste stimuli, which normally drive ingestion, reduce their input into feeding circuits when the animal is satiated.

The gustatory system

At the periphery, the gustatory system includes an array of taste buds in the oral and pharyngeal cavities. Taste buds are located around small structures known as papillae, which are found mainly on the upper surface of the tongue (but also on the soft palate, upper esophagus, cheek, and epiglottis). There are four known types of papillae: foliate, circumvallate, fungiform and filiform, distributed on different zones of the surface of the tongue (Fig. 1) [46]. Taste perception is the result of an interaction between sapid molecules and taste receptors in specialized epithelial gustatory cells present in taste buds [47]. Taste buds are located on the tongue and have a lifespan of 5–20 days [17].

On a functional level, the gustatory system works as a nutrient sensing system. It enables the detection, recognition, and discrimination of the five basic tastes – sweet, bitter, umami, sour and salty, which can be combined to form more elaborate taste sensations [48]. Salty and sour tastes are detected through ion channels (Na+ for salt and intracellular proton concentration for sour) [49,50]. Sweet, bitter, and umami tastes are mediated by G protein coupled receptors (GPCRs) [47]. The proteins called T1R1, T1R2 and T1R3 detect sweet and umami tastants, while T2Rs is specific to bitter. The combination of these receptors with their specific ligand (contained in the sapid molecule) triggers a series of intracellular reactions [36,51]. The sensory information is transmitted to the primary taste cortex via three cranial nerves that carry taste information from different areas: the facial nerve (VII) from the anterior two-thirds of the tongue; the glossopharyngeal nerve (IX), from the posterior one-third of the tongue; and the vagus nerve (X) from the back of the oral cavity. These sensations are then transmitted to secondary or associative cortical areas common to olfactory and gustatory sensations (Fig. 1) [14,46].

An important factor that plays a fundamental role in gustatory perception is saliva. Saliva is the first digestive fluid in the food canal. It is secreted by the salivary glands and poured directly into the oral cavity [52]. Saliva helps in chewing food, forming and swallowing the food bolus, and digesting starch (amylase) [53]. Saliva also serves as the solvent of sapid molecules, which need to be dissolved in order to be detected by the taste receptor cells. By detecting these molecules, the gustatory system provides qualitative information of the ingested food. It is estimated that about 2 ml of saliva are secreted every 15–20 minutes. A decrease in salivary flow leads to xerostomia (mouth dryness), which makes the detection of sapid molecules more difficult, complicates the action of mastication and swallowing and may cause oral problems such as mucositis or candidiasis [54].

Hair Cell Transduction

Although hydromechanical events produce organ of Corti vibration patterns that serve as the effective sensory stimulus for hearing and form the basis of the relationship between cochlear place and characteristic frequency (i.e., tonotopy), the hair cell is the central element of sensory transduction because it is the receptor cell, a mechanoreceptor that converts mechanical to electrical energy. The human cochlea has approximately 3500 IHCs and 12,000 OHCs with densities that correspond to approximately 86 IHCs/mm and 343 OHCs/mm, although considerable variability generally exists within the population.164,165 The lengths of OHCs increase continuously from the base of the cochlea to the apex, whereas the lengths of IHCs remain fairly consistent (Fig. 148.10C). Unlike some sensory systems (e.g., olfactory and somatosensory systems) in which primary afferent fibers display specialized peripheral endings designed to sense external stimuli and transmit that information directly to the CNS, the statoacoustic system, as well as the visual and gustatory systems, senses its environment by means of specialized epithelial cells, the receptor cells, that are housed in specialized peripheral organs (e.g., the cochlea, the semicircular canals, the otolith organs). Furthermore, receptor cells that serve the statoacoustic system are innervated by primary afferents and do not enter the CNS directly.

Linking the Neurobiology of Bitter Taste to Perception

The previous discussion provides a cursory description of the “hardware” of the gustatory system, with a focus on neural mechanisms underlying bitter taste. Most of what we have learned about the molecular aspects of bitter taste transduction has been from experimental animal models, mostly rodents.

However, without data defining the psychophysical properties of various taste compounds and their mixtures, we cannot link the underlying neurobiology with perception. In this regard, animal models are particularly useful because effects of very selective manipulations of the gustatory system can be studied in a highly systematic and quantitative way in a wide variety of tissues, including the nervous system, as well as on taste-related behavior. In such efforts, however, it is important to be mindful of several interpretive guidelines.73

First, when most people talk about “taste,” they are actually referring to flavor. Flavor can be considered the perceptual integration of signals from the gustatory, olfactory, and trigeminal systems.80 To the specialist, however, taste refers to the behavioral and physiologic consequences of stimulating taste receptor cells in the oral cavity. Accordingly, the potential for taste stimuli to activate nongustatory sensory systems, including those of a visceroceptive nature in the cases where the taste solutions are swallowed, must be considered.

Second, perception cannot be measured directly; it must be inferred from behavior. The veracity of that inference depends heavily on the procedure used to measure the behavior, whether studying animals or humans.

Third, taste function is multidimensional. The sensory/discriminative dimension encompasses stimulus identification, including the basic taste qualities of sweetness, sourness, saltiness, bitterness, and umami. The affective dimension involves the hedonic evaluation of taste stimuli, ultimately promoting or discouraging ingestion, which is perhaps most relevant to addressing the unpalatable nature of bitter medicines in children. Physiologic reflexes are also triggered by taste stimuli, such as salivation triggered by the oral sampling of a lemon. Thus, behavioral outcomes from a given gustatory manipulation need to be interpreted in light of the domain(s) being assessed.

Finally, a neuron’s response to an orally applied chemical stimulus does not, in and of itself, reveal the functional domain(s) to which the cell contributes. In this sense, behavioral observations are indispensable in understanding the neurobiological mechanisms underlying taste function.

Loss of Taste Perception

Decreased transfer of tastants by saliva to the receptor cells of the taste buds of the gustatory system, as well as possible coating of the tongue, as a result of microbial growth and accumulation of dead tissue and food debris, may interfere with the taste perception. Taste perception may be exaggerated if denuding of the tongue occurs as a result of loss of partial or total loss of papillae or alteration of the papillary architecture. Also, depending on type of medication use, there may be altered taste (eg, a metallic taste).

Dysgeusia

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Up to 85% of cancer patients report taste changes.40

These taste disturbances may be caused by damage to the gustatory system, loss or distortion of olfactory function, systemic co-diagnosis or local oropharyngeal conditions.41 Chemotherapy and RT may damage the taste buds directly or indirectly via the neurotoxic effects of chemotherapy or by changes in saliva quality caused by both chemotherapy and RT.

Additionally, targeted therapy, such as tyrosine kinase inhibitors, have been reported to cause dysguesia1,42

Dysguesia may be limited to certain types of taste. Altered taste or loss of taste may be experienced at rest, may limit oral intake, and has a marked impact on patient quality of life.

Taste sensitivity may recover within several months, but some studies describe long-term taste change. About 20% of patients reported taste change at 6 years after HSCT.43