Assignment 2- Research Paper Summary and Critique

Humans Can Taste Glucose Oligomers Independent of the hT1R2/hT1R3 Sweet Taste Receptor

Authors: Trina J. Lapis, Michael H. Penner and Juyun Lim

Summary

Introduction

                The main function of taste is to identify substances in the oral cavity, including food which provides energy or harmful toxins. Currently there are 5 generally excepted tastes; sweet, sour, bitter, salty and umami. Each flavour is known to use its own receptors and transduction pathways. Umami uses G-protein coupled receptors (T1R family) and metabotropic glutamate receptors, bitter uses G protein coupled receptors (T2R family), sour uses cyclic nucleotide-gated channels (HCNs), acid sensing ion channels (ASICS), and transient receptor potential channels (PDK2L1 and PKD2L3), and salty uses epithelial sodium channels (ENaC). The flavour with the most focus in this research is sweet, which utilizes G protein coupled receptors T1R2 and T1R3 (hT1R2/hT1R3 in humans). Recently the idea of the 5 main flavours has been changing with evidence towards flavour detecting of chemicals such as calcium, fat and starch products.

                It would be beneficial to animals and humans if starch had its own flavour and could be detected (due to the nutritional value), but it is unlikely as starch is a very long polymeric molecule. However, it is possible for starch hydrolysis products to be detected in the oral cavity after salivary amylase hydrolyzes it into simple sugars and oligomers. Previous studies have demonstrated the ability of humans to detect maltodextrin (polymer mixture) independent of sweet taste and rats to detect polycose (mixture of glucose oligomers and polymers) and differentiate it from sucrose. However, all previous studies have used mixtures and have not used accurate controlling factors to ensure accurate results.

                This experiment separated maltodextrin into 3 groups based on their degree of polymerization (number of monomers in the chain). Sample 1 (S1) had a DP of 7 (oligomer), sample 2 (S2) had a DP of 14 (oligomer), and sample 3 (S3) had a DP of 44 (polymer). The objectives of the study were to determine the lengths of glucose chains that can be detected, investigate a potential gustatory mechanism, establish glucose oligomer taste qualities, and create a dose-response curve for glucose oligomers. Each objective was the focus of one experiment in a series of 4 completed during this study.

Materials and Methods/Results

Experiment 1A – Taste Discrimination of Glucose Oligomer and Polymer Stimuli as equivalent % w/v solutions

It was required to stop the hydrolysis of the oligomers and polymers by alpha-amylase into simple sugars in order to get accurate results. In order to do this, an alpha-amylase inhibitor (acarbose) was used. Pilot experiments were completed to ensure that acarbose truly inhibited alpha-amylase (in average salivary concentrations, 5mM) when S1, S2, and S3 were present. This test was completed to determine what samples were able to be detected by human gustation, and it was predicted that S1 would have the greatest detection rate and S3 would have the lowest detection rate. 22 subjects (male and females) with an average age of 25 were used. The criteria for entering the experiment were that they were non-smokers, not pregnant, not medication takers, no history of smell or taste loss, no past oral disorders, no oral piercings, no recent dental work, no alcohol consumption in 12h, no food or beverage containing dairy within 4h, no food or beverage at all in 1h, and no products containing menthol within 1h. Solutions of 6% and 8% (w/v) were created, stored at 4-6 degrees Celsius, and returned to room temperature before testing. Each subject was put through 2 sessions (one 6% and one 8%) on different random days. The test consisted of 3 sip-and-spit tests (2 controls and 1 sample), where they sampled all 3 and had to identify the one with different flavours. In order to prevent olfactory input, they wore nose clips as well. This continued 3 times (one for each sample) and they rinsed with water in between, and the orders were counterbalanced and randomized. The results were added by number of correct identifications, which were statistically converted to d' values that accurately represented the stimulus and subtracted background results (noise). The prediction was shown to be accurate as the subjects could distinguish S1 and S2 from blanks, but not S3. d' values were also higher for S1 than S2, and were higher for the 8% samples than the 6% in both cases.

Experiment 1B- Taste discrimination of glucose oligomer and polymer stimuli as equivalent mM solutions

It was thought that the test results in experiment 1A may not have been accurate as the w/v ratios may have skewed the results in favour of S1 and S2 (as each mole of S3 weighs much more, therefore less molecules of S3 were present). This experiment aimed to correct this by testing samples with equal reducing ends (RE). The RE’s signify one oligomer or polymer, therefore it is a direct measurement of the number of molecules and would be more balanced. The problem arose when an S3 solution with the predetermined concentration of 75mM (8% w/v for S1, 17% w/v for S2, and 54% w/v for S3) became notably viscous. A blank was created with tasteless, viscogenic agent, methylcellulose to correct for this. 26 subjects were obtained with the same criteria as experiment 1A. All stimuli were prepared with 5mM of acarbose, and the blanks were created with consistent viscosity. The stimuli were also presented on cotton swabs to reduce further textural clues, although the pattern of experimentation remained unchanged. The results ended up being very similar, with subjects able to discriminate S1 and S2 from blanks, but not S3. Although contrary to prediction, the detection rate of S1 and S2 were actually almost equal, differing from experiment 1A.

 

Experiment 2- Taste Discrimination of sugars and glucose oligomers in the absence and presence of lactisole

It was also important to test if similar mechanisms of detecting simple sugars were used to detect glucose oligomers. In order to do this a chemical called lactisole was used (tasteless, sweet taste blocker that binds to hT1R3). 25 subjects were used with an average age of 25, with the same criteria as previous experiments. S1 and S2 samples were used, along with glucose, maltose and sucralose (artificial sweetener) to test for lactisole effects. Acarbose was added, and all target and blank stimuli were prepared with and without lactisole. 5 stimuli were provided, with and without lactisole (total of 10 tests), and pseudo-randomization was used as it was impractical to do all the possible combinations. The same cotton swab triangle tests were completed exactly as before, and results were analysed into d’ values. All 5 stimuli were equally detected in the absence of lactisole, but when lactisole was present it blocked the taste of glucose, maltose and sucralose. However, lactisole did not compromise the ability to detect the glucose oligomers. 

 

Experiment 3- Determination of taste quality of glucose oligomer through a focus group discussion

                

This experiment was aimed at subjectively describing the taste quality of the glucose oligomers, which had already been established as using different mechanisms of detection in experiment 2. 7 subjects who had already participated in one of the studies were used. Different amounts of equally intense aqueous solutions of sucrose, sucralose and S2 were provided using the cotton swab technique. In a focus group the subjects tasted the unknown stimuli and were asked to describe the flavour and, as a group, come up with a one word descriptor for the taste they were experiencing. It was seen that sucrose was “sweet” like sugar water, sucralose was “sweet” like artificial sweetener, and the glucose oligomer was “starchy” like a root vegetable, corn, bread, or pasta. Sucrose and sucralose were also identified as being much more similar than either sucrose or sucralose to the S2 oligomer.

Experiment 4- Establishing dose-response curves for sugars and glucose oligomers

                 

Once the new flavour was characterized, it was of interest to create a dose-response curve which could be compared to natural sweeteners. 20 subjects (mean age of 25) were recruited again with the same criteria. Sucrose, glucose and S2 were provided at 3 concentrations (45, 100, and 224mM) with acarbose present in all. The cotton swab technique was used again, and the subjects were asked to rate the intensity of a general version of the Labeled Magnitude Scale (gLMS) which they were previously trained to use. The data was plotted on a dose response curve based on molar and %w/v concentrations. These results showed that glucose and the glucose oligomer had almost indistinguishable curves based on moles, however, when using %w/v ratios, it was seen that glucose oligomers were shifted to the right of the glucose curve. 

Discussion

                Based on the results from experiment 1, it was seen that humans can discriminate glucose oligomers from water, but not glucose polymers from water. It is important to note that taste is not the only sense responsible for detection of glucose oligomers, although the other sense were controlled in these experiments (nose clips to reduce olfactory clues and similar textures to reduce somatosensory clues). It is also important to note that the breakdown of starch and glucose oligomers to simple sugars can contribute to the recognition of glucose oligomers in vivo, but this was constantly controlled for in every experiment using acarbose. A conclusion can be made that, in the absence of confounding effects, glucose oligomers can be sensed by the human gustatory system. Although these results conflict with previous studies which stated that rats can taste glucose polymers, the previous studies did not control for glucose polymer hydrolysis.

                Based on the results from experiment 2, it was seen that subjects lost the ability to taste glucose, maltose, and sucralose, in the presence of lactisole but did not lose the ability to taste glucose oligomers. As lactisole (which blocks T1R3 sweet receptors) did not stop the sensation of glucose polymers, it is clear that glucose oligomers use a different taste receptor. These results are consistent with previous finding where T1R2/T1R3 knockout mice could still taste glucose oligomers.

                These findings were backed up by evidence of experiment 3, where subjects rated the flavour of oligomers as “starchy”. In the past, other receptors have been thought to be used for detection of sugars and glucose oligomers, such as T1R-independent pathways. However, the findings in this study also disprove this theory, and it is now thought that there is a completely novel receptor used for starch hydrolysis products. The main function of this receptor is likely to identify incoming starch which has begun being broken down by amylase while entering the digestive system.

Personal Critique

This paper did an excellent job at covering all of the bases when determining the detection of starch hydrolysis products on the tongue. It reviewed many pieces of previous work done on this topic, and improved upon them by adding more controlling factors and doing multiple experiments to back up their theory. The use of acarbose as an amylase blocker was what differentiated this paper from the rest and seemed to produce more accurate effects and results. Experiment 1 was also repeated using different measurements in order to fully ensure that the results they obtain were accurate. Using step by step experiments (determining if humans could taste starts, and then determining if they could taste them without sweet receptors) was a very intelligent thing to do. If they relied on previous work, which stated that rats could taste glucose polymers, it may have skewed the results when they blocked the sweet receptors with lactisole. The experimenters also made it very clear that they completed a pilot study (ensures the chemicals were functioning accurately) whenever it was required. Although the results of this experiment were not specific (they did not find a receptor responsible for glucose oligomer detection), they did their best to lay down the groundwork for further research on this topic and ruled out some possible paths of research.  

In my opinion, experiments 1 and 2 were enough information to produce a paper on their own. The research completed in experiments 3 and 4 seemed unnecessary and generally not important to the main idea of the paper. Experiment 3 produced subjective flavour characteristics of the glucose oligomers which were deemed “starchy”, however this idea had already been demonstrated in the first 2 experiments. Experiment 4 created a dose-response curve for the concentrations needed to detect glucose oligomers, which could have been done in a separate paper, especially because the results were not even discussed in the discussion section. One important thing to note about the first 2 experiments are the small sample sizes that were used (about 25 people). Even though the data was statistically significant, it could have increased the validity of the research if more subject were used in each experiment. Other than these factors, I think the paper was well written and organized in a way that made sense. The results they obtained could open up a door into more research about flavour detection of not only glucose oligomers, but many other potential chemicals.

Reference

Lapis, T. J., Penner, M. H., & Lim, J. (2016). Humans Can Taste Glucose Oligomers Independent of the hT1R2/hT1R3 Sweet Taste Receptor. Chemical Senses, 41(9), 755-762. doi:10.1093/chemse/bjw088 

Note: All Figures and Images in this section were retrieved from this paper which can be found here.

Assignment 1: The Human Tongue

Function

The tongue is an organ that lies within the oral cavity in humans and many terrestrial vertebrates. The tongue is important in the functioning of multiple human processes and is very important in day to day life. Firstly, the tongue is one of the first organs which interact with food in the digestive tract. The tongue plays an important role in the process of mastication (chewing and grinding food) and begins the first step of digestion by breaking down some lipids [11]. The tongue pushes the food against teeth and the palate and aids in creating a bolus (ball) of food ready for further processing [5]. The muscular tissue is then used to send food from the oral cavity to the esophagus where it can proceed further into the digestive tract. 
Although digestion is probably the main function of the tongue, it is used for many more processes by humans and animals. The main focus of this blog is on the tongue as a sensory organ. The tongue plays an extremely important role in sensing chemicals which are in the oral cavity [5]. This sense is known as Gustation. Gustation along with the olfactory sense (smell), produce a combined sense that we refer to as taste [5].
Other functions of the tongue are a result of its capability of fine motor movement. Changing the shape of the tongue can allow animals to produce different sounds and allow humans to communicate through language (by allowing fine phonetic pronunciations which results in articulated speech) [5]. Some sources also list the tongue as a key organ involved in intimacy and sexuality, and is actually part of the erogenous zone of the mouth [5]. 

Structure

The tongue is a very muscular tissue that resides in the oral cavity in humans. The tongue can be separated into various sections due to physical lines of connective tissue or lines that divide structure and function of the tongue. Firstly the tongue is separated into nearly symmetrical halves into left and right sections by a dividing line of fibrous connective tissue called the lingual septum [8]. This dividing line produces a groove called the median lingual sulcus, which is visible when looking at the tongue with the human eye. 

Figure 1: Areas of the Tongue

Perhaps the more important dividing line however, is the V-shaped sulcus terminalis (terminal sulcus) which occurs approximately two thirds of the way from the apex of the tongue [8]. This is another apparent groove on the tongue, with a distinct apex called the foramen cecum (a developmental thyroid diverticulum remnant) [8]. The importance of the sulcus terminalis is not just dividing the tongue into two sections, but it signifies a change in the tongue structure and function as well. The tongue tissue before the sulcus terminalis is known as the anterior (oral) portion which functions in mastication and gustation, with many protrusions of the epithelium known as papillae [8]. The portion after the sulcus terminalis is the posterior (pharyngeal) portion which is mainly associated with immune function and is considered a tonsil, as it is covered with lymphoid tissue [8]. The two sections also differ in their development, blood supply (although both from lingual artery), and nerve supply, although both are derived from the pharyngeal arches during the 4th week of prenatal development [4]. 

Figure 2: Sulcus Terminalis

 

 

Development

Figure 3: Tongue Bud

As mentioned above the tongue starts its development during the 4th week of prenatal development. The problem with studying tongue development in humans is that it is very difficult to observe as it lies within the oral cavity. Although knowledge is limited, some information on tongue development does exist. It is known that the tongue appears to develop from the oral floor of the prenatal mouth, in a structure commonly referred to as the tongue bud [4]. The structures of the tongue can be mapped to the first 4 pharyngeal arches (arch 1= oral portion, arch 2= covering is lost, arch 3= pharyngeal portion, arch 4= epiglottis and surrounding tissue) [4]. The tongue epithelium and connecting tissues expand and grow during early development until the muscles are ready to be formed. Around week 10, the tongue muscles start to form from the somite mesoderm [4]. After this, the muscles continue development, the tongue expands its circumference, and the muscles are innervated during the 2nd trimester [4]. It is seen that the innervation of the tongue muscles is very complex and happens in large clusters. The most complex innervation occurs in the transverse muscles which form in the core of the tongue and are discussed later [4].  

Figure 4: Pharyngeal Arch Development

The frenulum is also an important tissue which forms and connects to the ventral surface of the tongue. During early development the lingual frenulum limits the movements of the fetal tongue to avoid damage. This function continues on until adulthood, but some issues may arise depending on how large the frenulum is. If the frenulum limits the movement of the tongue too much it leads to being tongue-tied (ankyloglossia), where impairments in speech and breast feeding may be seen [4]. 

Figure 5: Frenulum of the Tongue

Histology

The tongue is a primarily muscular tissue as the main function is to serve in mastication.The tongue has a highly convoluted epithelium, with associated taste buds and glandular tissue. The lamina propria of the tongue is seen to have dense, loose, and fibrous connective tissue as well as containing some adipose tissue [8]. 
 

Oral Mucosa

Figure 6: Tissues covered by Oral Mucosa in the Oral Cavity

Figure 7: Surfaces of the tongue under a light microscope

The oral mucosa (masticatory mucosa) is the general term used for the epithelium of the tongue along with its underlying lamina propria. Oral mucosa is not specific to the tongue, but is generalized to the lining of the oral cavity, including the palate, cheeks and throat as well [7]. Some of the oral mucosa is specialized for rapid absorption of certain chemicals (ie, sugar for diabetics) or drugs [7]. Most of the epithelium of the tongue is composed of keratinized stratified squamous epithelium [4]. This type of epithelium is normally found on the dorsal surface (dorsum) of the tongue, where there are not protrusions (papillae) and in the presence of filiform papillae [7]. This tough surface allows the tongue to grind and chew food without obtaining mechanical damage to itself. The epithelium also functions to keep out certain bacteria so that infections cannot occur. Some surfaces of epithelium in the tongue are non-keratinized. This type of epithelium occurs on the ventral surface of the tongue, where mechanical damage is unlikely [7]. Non-keratinized epithelium is also usually associated with papillae on the dorsal surface [7]. This difference in epithelium types, along with the presence or absence of papillae, is why the tongue feels rough on the dorsal surface and very smooth and mucous-like on the ventral surface. The lamina propria, also known as the corium in the tongue, is filled with connective tissue, adipose tissue, and minor salivary glands with an abundance of muscle tissue directly underneath filling the majority of the tongue. 

 

Papillae  

Figure 8: Locations of Each type of Papillae

Papillae are large or small protrusions of epithelium on the tongues dorsal-oral surface. Between papillae are large spaces known as crypts, where chemical signals can interact with taste buds on the medial surface of the papillae. There are 4 major types of papillae based on their shape, size, and function. The first type are known as filiform papillae, which are keratinized filim or thread-like protrusions [8]. These are the most common papillae found on the human tongue and are not associated with taste buds at all. The function of filiform papillae is likely to aid in mastication and to help secrete some glandular material [8]. The second type are known as fungiform papillae, because of their mushroom-like shape [8]. These papillae are non-keratinized and are normally associated with taste buds, likely serving a gustatory purpose. The third type are known as the vallate (circumvallate) papillae which mainly appear along the lining of the sulcus terminalis and appear circular in shape [8]. These papillae are associated with taste buds, but function mainly to secrete serous secretions produced by specialized glands that surround them [8]. The last type are the foliate papillae, due to their leaf-like appearance. These papillae are extremely uncommon in humans, and appear mainly on the sides and back of the tongue (some people do not have any) [8]. They are non-keratinized and are associated with an abundance of taste buds. 

Figure 9: 4 Types of Papillae

 

Glandular Tissue

 The oral cavity produces many mucous and serous secretions which produce what is generally referred to as whole saliva [11]. The glands generally found in the oral cavity are mucous secreting, which contribute to the massive volume of saliva produced in a day. Associated with the tongue however, are specialized glands which have a separate purpose. Known as Von Ebner's Glands, or serous fluid producing minor salivary glands, this glandular epithelial tissue is specialized to hydrolize lipids found in vallate and foliate papillae [11]. Von Ebner's glands produce and secrete a fluid (much more watery than mucous) which contains enzymes called lingual lipases [11]. These are the enzymes responsible for one of the very first step in digestion, as they begin to break down lipid molecules. Von Ebner's glands are also thought to aid in taste perception as the fluid washes away any remaining chemical stimuli and creates an environment where a new stimuli can enter [11]. This means that these secretions are likely the reason that humans can respond to quickly changing stimuli. 

Figure 10: Von Ebner's Glands

 

Muscular Tissue 

The muscles in the tongue are skeletal muscles that fall into multiple different planes, which allow the tongue to be capable of many unique and specific movements. In general the tongues skeletal muscles fall under two categories: Intrinsic and Extrinsic [1]. There are 4 main muscles of each category, for a total of 8 large muscles in the tongue. 
Intrinsic muscles are the muscles responsible for delicate movements and specific movements [1]. This means that these muscles are mainly active when the tongue needs to be moved in a precise manor, such as during speech. The four main intrinsic muscles are as follows: 

Figure 11: Intrinsic Muscles of the Human Tongue

1. Inferior Longitudinal Muscle: spans the length of the tongue (longitudinally) and is responsible for moving the apex of the tongue, and responsible for some shortening of the tongue [1]. 
2. Superior Longitudinal Muscle: Spans the length of the tongue and is responsible for moving the apex in cooperation with the inferior longitudinal muscle [1].
3. Transverse Muscle: Spans across the tongue and is responsible for narrowing the tongue [1].
4. Vertical Muscle: Spans from the dorsal to ventral surface of the tongue and is responsible for flattening the tongue [1].

 The extrinsic muscles use very strong tongue-root tension in order to contract the tongue with outstanding strength. These muscles are all connected to some bone (in the jaw or skull) and are responsible for strong contractions necessary for swallowing and mastication [1]. Much like the intrinsic muscles, there are 4 extrinsic muscles in the tongue as follows:

Figure 12: Extrinsic Muscles of the Human Tongue

1. Hyoglossus: Connects the hyoid bone to the tongue and is responsible for retracting and depressing the tongue [1].
2. Palatoglossus: Connects the palate to the tongue and is responsible for pulling the tongue back to its groove [1]. 
3. Styloglossus: Connects the styloid process (behind the ear) to the tongue and is responsible for pulling the tongue upwards and towards the esophagus [1].
4. Genioglossus: Connects the chin to the tongue and is responsible for sticking the tongue out and pulling it back. This muscle is also responsible for "troughing" the tongue [1].

       

The Taste Buds

Figure 13: Light Microscope image of Taste Buds

Structure

Taste buds are specialized receptor clusters which appear in the epithelial layer of some papillae in the tongue in terrestrial animals, but also appear on the lips, flanks and caudal fins of some fish species [9]. A papillae which contains taste buds is commonly referred to as a taste papillae. There are approximately 2,000-8,000 taste buds in the human tongue, although immense variation is seen between individuals [9]. 
Taste buds are unlike  many other receptor structures as they are mainly derived from precursor cells which are part of the epithelium [2]. Most other receptors in the human body are derived from nervous tissue, which has sparked some interest in taste receptor cells and their development. Further studies have confirmed that the majority of taste bud cells originate from the epithelium, although recent research has suggested a strong link between taste bud development and neural crest cells [2]. There has also been evidence to suggest a precursor which is apparent in the underlying connective tissue cells [2]. 
The traditional view of a taste bud was that it was a collection of 50-150 taste receptor cells which cluster together [9]. These taste buds have microvilli on their apical surface which reach out through small taste pores. The microvilli are covered in mucus, which brings chemical stimuli to the microvilli where they are sensed [9]. The signal is then sent through the cell and attaches to a neuron on the basal surface. 

Figure 14: Traditional View of Taste Bud Structure

 Modern views of the taste bud recognize that there are multiple different cells which all make up the structure of the taste bud. There are taste receptor cells, which function as stated above, but also a variety of assistant cells. These cells include basal cells, which function as taste receptor cell precursors, as taste buds are recycled very frequently [9]. Support cells are also now recognized, which have no sensory function but exist for structural and nutritional support [9]. The biggest difference between this view and the last is that there is a single cell, called the presynaptic cell, which receives all the signals from the other receptors, combines them and sends the signal to the neuron [9]. It is completely possible that both of these views on taste bud structure are accurate, and that the different types exist in different areas of the tongue, although very little research has supported this. 

Figure 15: Modern Proposed View of Taste Bud Structure

Function

Figure 16: Biochemical functioning of the Taste Bud Receptors

The first step to taste bud functioning is the stimuli being received by the receptor cells. The chemicals which bind to receptors in the taste bud cells are commonly referred to as "tastants" [10]. These tastants are collected in the mucous on the tongue, where they are fed in and out of the crypts between the papillae. Typically, a tastant reaches the microvilli of the taste receptor cells where taste receptors occur in large numbers [10]. It has also been recently discovered that the apical and basal surface of the taste receptor cell body can house taste receptors and respond to chemical tastants [10]. 
The receptors on a taste cell are what respond differently to various chemicals, and produce different "flavours". These receptors work much like neurons receiving a neurotransmitter signal. When the tastant stimulates the receptor, it causes opening of a channel (ionotropic) or changes in the cells metabolism through G-protein manipulation (metabotropic) [10]. 
Different receptors exist for the 5 main flavours we know today; salty, sweet, sour, bitter and umami.

Figure 17: Mammalian Taste Receptor Structures

1. Salty Receptors: epithelial-type sodium channel, which responds to different concentrations of sodium ions in the environment. Protons also may use these channels, explaining why eating acidic food reduces the saltiness of others [10].
2. Sweet and Sour Receptors: these involve activation of G-protein linked receptors. Different pathways are used for specific sweeteners, which is how natural and artificial sweeteners may taste different [10].
3. Bitter Receptors: Bitter tastants come in many classes (alkaloids, amino acids, urea, and some salts). These each use different receptors and pathways usually involving a specific G-protein called gustducin. If gustducin is non-functioning, bitter flavours will not be apparent [10].
4. Umami Receptors: The umami flavour has only been recently discovered and has not been researched in much detail. It is thought to be a response to certain amino acids (specifically glutamate) which produce a savoury flavour. There are though to be many different pathways for umami [10]. 

From this point the taste receptor cells change in their metabolic or ionic functioning which typically causes an influx in calcium ions. Much like neurons, this causes a release of neurotransmitters, which stimulate a neuron or another taste bud cell. The two proposed structures play a role in how this signal is transmitted, but either way the signal is transmitted to multiple neurons which are brought to the brain through the facial, glossopharyngeal and vagus nerves [9]. It is important to note that the extreme variation in taste bud receptor cells within a taste bud, and the random distribution of these taste buds is what produces the wide variety of flavours humans can taste. The common "taste map" where each flavour resides is not accurate as taste receptors vary too much and have no common distribution on the tongue [9].

The Tongue and Taste Buds Pathology

The tongue and taste buds have many diseases, ranging from bacterial and fungal infections, to general defects in their receptors. The following diseases are common in the tongue, but many are harmless to humans. WARNING: some of the pictures associated with the diseases will be gross, continue if you wish. 
 
Thrush (cadidiasis): Caused by a yeast (Candida albican) which grows over the surfaces of the oral cavity, including the tongue [5]. Thrush usually occurs in individuals with suppressed immune systems, although it can occur in anyone. Thrush can be treated using topical anti-fungal treatments or systemic oral azoles [3].

Figure 18: Candidiasis

Oral Cancer: Like most other cancers, where a growth or ulcer appears on the tongue. Oral cancer has been linked to certain habits, such as smoking or drinking alcohol [5]. 

Figure 19: Oral Cancer

Macroglossia: This disease is also known as "big tongue". Macroglossia is exactly what it sounds like, it is a swelling or overgrowth of the tongue [5]. It can be caused during development by congenital defects, or later in life by inflammatory, traumatic, cancerous and metabolic causes [5]. 

Figure 20: Macroglossia

Geographic Tongue: This disease is named so because of the geographic appearance of tongues with this condition. The tongue appears cracked with ridges and coloured spots which move across the tongue's surface. Geographic tongue is typically harmless and is mainly caused by dehydration (can be mild, as in "dry mouth" in the morning) [5].

Figure 21: Geographic Tongue

 

Burning tongue: This is a syndrome in which there is a constant or erratic feeling of the burning or scalding of the tongue. This can be a symptom of underlying nerve damage, but is usually not the disease itself and is rarely treated alone [5]. 

Figure 22: Burning Tongue Syndrome

 
Atrophic Glossitis: This disease is also called "bald tongue", because of the naked appearance of the tongue. The normal ridges and texture caused by the papillae disappear, as the papillae themselves lose their structure. This is commonly associated with a vitamin B deficiency and is also seen in anemic patients [5]. 

Figure 23: Atrophic Glossitis (Bald Tongue)

Hairy Tongue: This condition is almost the exact opposite of bald tongue. The papillae on the tongues surface can overgrow, creating an extremely ridged looking tongue, almost appearing hairy [5]. The treatment for this is usually to physically scrape off the excess papillae [5].

Figure 24: Hairy Tongue

Ageusia/Dysguesia: Dysguesia is a reduction in the ability to taste, whereas Ageusia is the complete loss of gustatory sensation altogether [6]. Ageusia is typically not associated with the taste buds themselves, but rather the other senses which determine flavour, specifically olfaction [6]. Non-olfactory ageusia can occur through damage to the taste buds or the nerves which transmit the signals from the tongue to the brain. Non-olfactory ageusia can be caused by local (oral infection, dentures, radiation), systemic (cancer, renal failure, liver failure), or neurological (Bell palsy, MS, viral infection) factors [6]. Ear damage can actually cause ageusia as it can potentially damage the chorda tympanii [6]. Hypoguesia also exists where taste perception is greatly increased [6].



References

[1] Articulation: The Tongue. (n.d.). Retrieved October 18, 2016, from http://www.yorku.ca/earmstro/journey/tongue.html

[2] Boggs, K., Venkatesan, N., Mederacke, I., Komatsu, Y., Stice, S., Schwabe, R., . . . Liu, H. (2016, January 7). Contribution of Underlying Connective Tissue Cells to Taste Buds in Mouse Tongue and Soft Palate. PLoS One, 11(1).

[3] Candidiasis Treatment & Management - Medscape Reference. (2016, October 6). Retrieved October 18, 2016, from http://emedicine.medscape.com/article/213853-treatment

[4] Hill, M. A. (2016). Tongue Development - Embryology. Retrieved October 18, 2016, from https://embryology.med.unsw.edu.au/embryology/index.php/Tongue_Development

[5] Hoffman, M. (n.d.). The Tongue (Human Anatomy). Retrieved October 18, 2016, from http://www.webmd.com/oral-health/picture-of-the-tongue#1

[6] Kieliszak, C., Peterson, A., & Joshi, A. (n.d.). Ageusia | 5-Minute Clinical Consult - Unbound Medicine. Retrieved October 18, 2016, from http://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/816154/all/Ageusia

[7] Oral Mucosa | myVMC. (2015, May 14). Retrieved October 18, 2016, from http://www.myvmc.com/anatomy/oral-mucosa/

[8] Peckham, M. (n.d.). Tongue Oral Tissue: Papillae of the Tongue Anterior Surface of the Tongue. Retrieved October 18, 2016, from http://www.histology.leeds.ac.uk/oral/tongue.php

[9] Taste Buds. (n.d.). Retrieved October 10, 2016, from https://www.britannica.com/science/taste-bud

[10] Taste Receptors and the Transduction of Taste Signals ... (n.d.). Retrieved October 10, 2016, from https://www.ncbi.nlm.nih.gov/books/NBK11148/

[11] Varun. (n.d.). Minor Salivary Glands Types, Locations, and Functions. Retrieved October 18, 2016, from http://www.juniordentist.com/minor-salivary-glands-types-location-and-function.html