When there is a perturbation in the balance between hunger and satiety, food intake gets mis-regulated leading to excessive or insufficient eating. In humans, abnormal nutrient consumption causes metabolic conditions like obesity, diabetes, and eating disorders affecting overall health. Despite this burden on society, we currently lack enough knowledge about the neuronal circuits that regulate appetite and taste perception. How specific taste neuronal circuits influence feeding behaviours is still an under explored area in neurobiology. The taste information present at the periphery must be processed by the central circuits for the final behavioural output. Identification and understanding of central neural circuitry regulating taste behaviour and its modulation by physiological changes with regard to internal state is required to understand the neural basis of taste preference. Simple invertebrate model organisms like Drosophila melanogaster can sense the same taste stimuli as mammals. Availability of powerful molecular and genetic tool kit and well characterized peripheral gustatory system with a vast array of behavioural, calcium imaging, molecular and electrophysiological approaches make Drosophila an attractive system to investigate and understand taste wiring and processing in the brain. By exploiting the gustatory system of the flies, this chapter will shed light on the current understanding of central neural taste structures that influence feeding choices. The compiled information would help us better understand how central taste neurons convey taste information to higher brain centers and guide feeding behaviours like acceptance or rejection of food to better combat disease state caused by abnormal consumption of food.
- neural circuits
- gustatory receptors
- feeding behaviour
The sense of taste is a fundamental sensory modality for all animals. It controls many behavioural decisions by processing and integrating information from the periphery. In all animals, gustatory system plays a critical role in evaluating the nutritional value of food. The sense of taste warms animals against consumption of spoiled/fermented or toxic compounds and orchestrate appetitive responses to energy, protein and calorie-rich food sources.
In humans, taste buds on the tongue can differentiate between the five basic tastes: sweet, sour, salty, bitter, and umami (a savoury taste) by processing the taste information in the brain. These are important building blocks for our understanding of flavour. Animals show attraction towards low salt, sweet and umami taste and aversive behaviour towards high salt, bitter and sour foods. Such responses are innate and largely invariant throughout animal’s life suggesting physiological hard-wiring of taste quality to hedonic value.
For decades, flies have been used as a genetically accessible system to study molecular mechanisms that coordinate feeding behaviour with sensory signals. They show an array of feeding characteristics that can be easily exploited for various behavioural and physiological analysis. Identification of gustatory chemosensory receptors has provided a major impetus in understanding taste signal transduction [1, 2, 3, 4, 5]. Gustatory sensory neurons located in external mouth region as well as internally in the pharynx project to sub esophageal zone (SEZ-a region implicated in feeding and taste) [5, 6, 7, 8]. Much less is known about the organization of the SEZ. Very few neurons that connect SEZ to higher brain centers have been identified. These circuits represent critical higher-order features of gustatory system including various set of interneurons, projection neurons, modulatory neurons and motor neurons that help flies to process and integrate peripheral taste signals. Although recently, many studies have focused on understanding how gustatory neural circuits are spatially organized to represent information about taste quality. Yet, the role of various regions in the central nervous system (CNS) in integrating feeding behaviour with sensory signals on the availability and quality of nutrients is currently insufficiently understood. How central taste circuits play an important role in health and disease is still undetermined. In this chapter, we have assimilated the information together to present a map of various taste circuits identified in the past few years beyond the level of primary taste neurons specifically in
2. Central taste circuits in humans
Tongue is the peripheral taste organ of the human taste system essential for tasting, chewing, swallowing and speech [9, 10, 11]. Tiny bumps present on the tongue called papillae give the tongue its texture. Many thousand taste buds cover the surfaces of the papillae that respond to taste and transmit that information from periphery to the CNS . Different types of papillae are present on the tongue classified as circumvallate, fungiform, filiform and foliate. All except the filiform papillae are associated with taste buds. The most common mushroom-shaped fungiform papillae cover two third of the tongue and are involved in detecting taste. They also contain sensory cells for detecting touch and temperature. The human taste system, along with the olfactory and trigeminal systems, helps in identifying and controlling the nutrient versus toxic compounds that finally leads to acceptance and rejection behaviour [9, 12]. Inside the mouth, the chemical components of food interact with taste receptors cells located inside the taste buds on the tongue and evaluate the quality and intensity of the taste. The other areas where taste cells are present includes the back of the throat, and at the junction of the hard and soft palates, epiglottis, the nasal cavity, and even in the upper part of the esophagus [13, 14]. The current findings also suggest nutrient sensing and presence of taste receptors in the gut [15, 16, 17, 18].
Taste buds are generally present as clusters of 50-100 polarized neuro-epithelial cells which can detect nutrients and other chemical compounds. They have numerous sensory cells that are in turn connected to many different nerve fibres [12, 19]. The first stage of gustatory signal processing starts with the taste buds. They communicate using electrical coupling via gap junctions and by cell to cell chemical communication via neurotransmitters including glutamate, serotonin, and ATP among other possible transmitters [20, 21]. Taste receptor cells get consistently replaced in taste buds to compensate the injury of the gustatory epithelia . Several afferent nerves carry specific sensory information from a specific peripheral region. The chorda tympani (CT), a branch of the facial nerve (cranial nerve VII), transmits gustatory information from fungiform papillae, while the lingual branch of the trigeminal nerve (cranial nerve V) carries information from fungiform about pain, tactile, and temperature and filiform papillae in the same area [23, 24]. Multimodal information including taste, tactile, pain, and thermal cues get conveyed from circumvallate papillae by the glossopharyngeal nerve (cranial nerve IX), from palatal taste buds by the greater superficial petrosal nerve (GSP, another branch of VII), and from the throat by the superior laryngeal branch of the vagus (cranial nerve X) [25, 26, 27, 28]. Foliate papillae are innervated by the CT (taste) and V (tactile) in anterior regions and by IX (multimodal) in posterior regions [29, 30]. All together taste and oral somatosensory cues combine centrally with retro nasal olfaction to generate the composite experience of taste .
The entire human taste system includes both peripheral receptors and central pathways. As afferent taste signals ascend the brain from caudal to rostral, the information flow split between the ventral forebrain and more dorsal thalamo-cortical regions where primary and secondary gustatory cortices (opercular, insular, orbitofrontal) give rise to conscious taste sensation [32, 33, 34]. Taste qualities, attention, reward, higher cognitive functions and multiple-modal sensory integration are managed by multiple secondary and tertiary cortices that are involved in the dorsal pathways [20, 35, 36]. While sensory processing at the extent of the taste bud is complex, the information transfer to the CNS via marked line . A gustotopic map has been produced when taste signals extend to the insula of the gustatory cortex . Each individual taste has a representation in the insular cortex by fine-tuned cells organized in a precise and spatially ordered taste map with each taste quality encoded in its own stereotypical cortical field .
The final step in perceiving taste is relaying the taste information collected by taste cells to the central nervous system via cranial nerves VII (Facial), IX (Glossopharyngeal), and X (Vagus), where there is a topographical representation of the oral cavity within the first nuclear relay, the solitary tract nucleus, in which brainstem reflexes of acceptance and rejection are controlled (Figure 1) . The taste cells within the taste buds transduce the stimuli from the ingested food and provide additional information about the identity, concentration and pleasant or unpleasant quality of the substance . Taste nerve fibers on stimulation by the binding of chemicals to their receptors, depolarize, resulting in an action potential that gets ultimately transmitted to the brain . This information also prepares the gastrointestinal system to receive food by causing salivation and swallowing (or gagging and regurgitation if the substance is noxious). The principal receptors involved to transduce human sweet stimuli are T1R2/T1R3, T1R1/T1R3 for umami stimuli (although mGluR1, mGluR4 and NMDA have been implicated), and T2R family for bitter taste stimuli. Growing evidences have suggested the role of epithelial sodium channel (ENaC) in part, in transducing salty taste, and acid sensing ion channels (ASICs) for sour taste stimuli [20, 40, 41, 42].
The ventral pathways are involved in autonomic and visceral functions, affective and emotional processing, memory and learning [43, 44] and ultimately, the informational content and values of the ventral and the dorsal pathways integrate . The circuitry is such that the cells make synaptic connection with primary sensory axons that run in the chorda tympani and greater superior petrosal branches of the facial nerve. The taste cells in fungiform papillae on the anterior tongue are innervated exclusively by the chorda tympani branch of the facial nerve. In circumvallate papillae, the taste cells are innervated entirely by the lingual branch of the glossopharyngeal nerve and in the palate they are innervated by the greater superior petrosal branch of the facial nerve . The lingual branch of the glossopharyngeal nerve and the superior laryngeal branch of the vagus nerve project into the rostral portion of the nucleus of the NST. The central axons of these primary sensory neurons in the respective cranial nerve ganglia project to rostral and lateral regions of the medulla [47, 48]. Secondary cortical taste area in the orbitofrontal cortex, present in the frontal lobe of the brain is responsible for decision making . Here, single neurons respond to combinations of chemosensory, somatic sensory, olfactory, and gustatory stimuli and even visual information . Information about the temperature and texture of food transmit from the mouth via the cranial nerves to the thalamus and somatic sensory cortices .
In the orbital cortex, feeding to satiety with one food reduces the responses of those neurons to that particular food only suggesting computation of sensory-specific satiety in the orbitofrontal neurons . Hypothalamic nuclei project to and receive input from other extra hypothalamic brain regions such as the nucleus of the solitary tract (NTS) to regulate food intake and energy expenditure [52, 53, 54, 55, 56, 57, 58]. Hunger, satiety and food consumption neural regulations are directly control by the genetic influence on human obesity . High sweet tastes are attractive while high bitter tastes are aversive, even in decerebrate animals and anencephalic humans [59, 60]. The brain ascent from caudal to rostral by the afferent taste signals where the information start breaking between the ventral forebrain and more dorsal thalamo-cortical regions then later opercular, insular, orbitofrontal (primary and secondary gustatory cortices) bring the awareness to taste sensation .
Taste pathways in the CNS are intimately connected with general viscero sensory sensory nerves from the cardiovascular, respiratory and, importantly, gastrointestinal systems . Circulating metabolic signals modulate neural responses in relays of the taste system, such as the NTS, and in areas that receive direct or indirect gustatory afferents like the hypothalamic homeostatic centers and reward-related areas in the midbrain . Vagus in particular contain afferent neurons that transfer mechanical and chemical sensory information from the gastrointestinal tract (GIT) to the brain. The neural transmission of chemical information could result from recognizing signalling peptides, such as CCK, produced by enteroendocrine epithelial cells with chemo-sensing properties .
Although a great deal of information has been generated but elucidation of how taste intensity is encoded in the insular cortex is necessary to address. It is still unknown whether taste qualities with similar valence project to common targets in the brain. Tracing the connectivity of each basic taste qualities to higher brain areas is still incomplete and will help decipher how these integrate with other modalities and combine with internal and external state for the final behavioural output. Hopefully understanding taste circuits in simple invertebrate model systems like
Drosophilagustatory system and circuits
In the olfactory system of the adult fruit fly, the structure and function of the neural circuits involved in detecting and processing olfactory information are well known. Approximately 50 different classes of olfactory receptors neurons express a particular type of olfactory receptor. The olfactory sensory neurons expressing the same receptor projects its axon to a single glomerulus in the antennal lobe of the fly where synaptic association with projection neurons and local interneurons occurs. The projection neurons transfer processed sensory information from the glomeruli to higher order brain centers including mushroom bodies (MB) and lateral horn (LH) which further process olfactory information for behavioural functions such as learning and memory or appetitive and inhibitory response control [64, 65, 66].
On the other hand, the identified central taste circuits of the gustatory system of
DrosophilaSEZ is the first relay of taste information
Drosophilasweet taste feeding circuits in the brain
SEZ has been shown to play a key role in gustatory signal transduction and feeding responses in different insects.
Additionally, to understand the central taste circuits in the fly brain that are involved in feeding decisions and different aspects of feeding behavior few second order neurons have been identified in the past few years. The first set of sweet gustatory projection neurons (sGPNs) marked by
Another genetic screen identified pair of 12 cholinergic local interneurons to characterize
6. Bitter taste circuit in the brain
The bitter taste modality is conserved in insects and mammals. It plays a key role in evoking aversive behavior in animals [32, 66, 68, 96]. Bitter sensitive gustatory interneurons (
Three classes of taste projection neurons (TPNs) have been identified based on their morphology and taste selectivity  named as TPN1, TPN2 and TPN3 (Figure 3D). TPN1/TPN2 neurons respond to sweet taste and promotes PER (innate feeding behavior) while TPN3 is bitter responsive and inhibits PER. TPNs are long-range projection neurons that separately carry sweet (TPN1 and TPN2 selectively relay sugar taste detection from the legs) or bitter information to higher brain demonstrating modality-specific relays. TPN3 responds to bitter taste on the legs and the proboscis, suggesting aversion to bitter compounds may not require specific location. Their data suggests that taste detection from different organs serves different functions, consistent with other studies where interneurons sense sweet taste from the mouthparts and drive ingestion . The organ-specific and modality-specific connectivity of TPNs demonstrates a mechanism to encode both taste location and taste quality. As both TPN2 and TPN3 send axons to the superior lateral protocerebrum (SLP) (Figure 3D) suggesting that information from the higher brain feeds back onto sensorimotor circuits for PER. Functional link from TPNs to mushroom body (learning and memory centers) has been postulated based on the presence of their arbors in the SLP and lateral horn, which further excite or inhibit MB extrinsic neurons. Reciprocal and bidirectional interactions between SLP and MBs for learned associations have also been shown previously . Conditional silencing of TPNs suggested that TPNs are not essential for proboscis extension and contribution from other neurons must contribute to this behavior but TPN2 and TPN3 are essential for conditioned taste aversion. Inhibition of synaptic transmission in sugar-sensing TPN2 during either training or testing decreased conditioned aversion, whereas inhibiting bitter TPN3 decreased aversion only if inhibition occurred during training. The modulatory role played by TPNs without being essential components of PER circuits require future investigation. These studies demonstrate modality-selective taste pathways to higher brain.
In a separate study, a pair of interneurons (PERin neurons, Figure 3C) are identified that activate by stimulation of mechanosensory neurons inhibiting feeding initiation. Conversely, inhibition of activity promotes feeding initiation and inhibits locomotion suggesting such neurons suppress feeding while the fly is walking . The dendrites of these neurons reside in the first leg neuromeres whereas axons are found in both SEZ and first leg neuromeres suggesting that they process information from the legs and convey to SEZ. These neurons do not make synaptic connections with known neurons that regulate proboscis extension. This study highlights that feeding initiation and locomotion are mutually exclusive behaviours and identified pair of interneurons influence this behavioural choice.
A receptor-to-neuron maps of pharyngeal taste organs reveals the presence of multiple classes of taste neurons , consistent with the knowledge that the pharynx may independently assess food quality. In this study use of
7. Central neurons controlling regurgitation
In another genetic screen to understand how sensory information is translated into behavior, a subset of higher order neurons labeled by
8. Higher order taste circuits involved in taste learning and memory
Based on their axonal arborizations in the α/β, α’/β’, and γ lobes, the KCs of the MB are divided into three main classes (Figure 4B). Evidences have identified that functional specializations among and within the classes, with different subsets playing different roles in the phase, type, and length of associative memory . Evidence that the MB processes tastes as CS and US (unconditional stimulus) comes from behavioural taste conditioning experiments [109, 113]. A simple taste behavior is the proboscis extension response (PER): when leg gustatory neurons detect sucrose, the fly extends its proboscis to eat. Pairing sucrose stimulation to the leg (CS) with an aversive stimulus (US) causes short-term inhibition of proboscis extension. This learned behavior requires the MB, but the neural processing in the MB that underlies taste conditioning is unknown. To gain insight into sensory processing, taste representation and role of these structures in aversive taste conditioning in the MB, behavioural and high end imaging studies reveal that the gustatory information in the main calyx are segregated and have unique representation by different taste modalities and different taste organs . Such inputs get differentially and independently modified by learning. Selectively blocking the γ lobe neurons leads to complete elimination of conditioned aversion suggesting role γ lobe as the site for aversive taste memory formation in the MB. The study also demonstrates the requirement of MB neurons for taste conditioning and taste information relayed to the MB is via multiple pathways. Only taste stimulation (bitter compounds and sucrose) activates the dorsal accessory calyx which has been implicated in gustatory processing in other insects earlier  providing evidences that gustatory MB representation is distinct from olfactory cues. These studies have extended the understanding of the neural coding underlying conditioned learning in the MB as a sensory integration center in the fly brain.
9. Motor neuron circuit
Interneurons are the local circuit neuron of CNS that relays impulses between sensory neuron and motor neuron while a neuron that passes from CNS or a ganglion towards a muscle and conducts a nerve impulse resulting in movement is known as motor neuron. The process by which brain process the sensory information into motor actions is not well acknowledged. A major step in most of the sensory-motor transformations is to convert the coordinates of sensory system into a map of spatially directed motor actions.
Proboscis is the primary feeding organ of flies and also plays an important role for taste cue detection and food ingestion and show reliable PER by applying positive gustatory stimulus to GRNs [67, 109, 115, 116]. PER represents an innate, sequential behavior involving many movement steps . PER sequence may require activation of different muscle groups at distinct time points, implying a defined temporal organization of upstream motor neuron (MN) activity. It has been proposed that the relay of gustatory sensory information from GRNs to MNs occurs mainly within the SEZ [67, 72, 117, 118, 119]. The motor neurons innervating proboscis musculature have been portrayed in fruit fly and blow fly [120, 121]. There are 15 paired proboscis muscles found in blowfly and 17 in
A pair of neurons that generate feeding motor program and induces the entire feeding sequence when activated are identified in
One of a study revealed that the mouth mechano-reception can ease and end feeding by two distinct central motor circuits and these two mechanosensory circuits merge with bitter taste in opposing manners to shape feeding behavior. Mechanosensory neurons (MSNs) were identified in taste pegs and taste bristles of the labella which rely on the same mechanoreceptor, NOMPC (No mechanoreceptor potential C) to transduce mechanical drift. The optogenetic arousal of bristle MSNs induce labellar spread, while activation of peg MSNs induces proboscis retraction .
Another pair of motor neurons involved in taste behavior has been identified to identify the components of the PER circuits. These neurons activate by sugar stimulation and inhibit by bitter stimuli . The bilateral pair of E49 motor neurons are both necessary and adequate to initiate proboscis extension reflex. Although these neurons synapse on proboscics musculature and show wide dendritic field in SEZ but otherwise are shown to make no direct connections with GRNs . In
In a separate study, analysis of sequential features of the motion pattern of PER provided morphological description of proboscis motor neurons and muscles . By implying genetic manipulations along with artificial activation and silencing process, five motor neuron types that control the key steps of proboscis extension are identified, lifting of the rostrum (MN9), extension of the haustellum (MN2), extension of the labella (MN6), spreading of the labella (MN8) and proboscis retraction (MN1) (Figure 5A). The above-mentioned steps are independently controlled in a one-to-one manner with the majority of MNs both sufficient and required for the execution of one individual step of the forward reaching behavior.
Remarkable specificity has been observed for candidate higher-order neurons in terms of the sensory neurons that activate them (proboscis versus mouthparts) and the behavioural subprograms they generate i.e. proboscis extension versus ingestion. The identification of these neurons suggest taste information is processed by parallel labelled lines via several different neural streams that coordinate different aspects of feeding behavior. Another behavioural study of the function of different taste neurons on the legs found that some cause inhibition of locomotion whereas others promote proboscis extension . This study highlights that sweet taste receptor neurons of legs are essential for sugar choice and highlighted a functional dissociation between and within taste organs of
10. Modulation of feeding behaviors via taste circuits
Taste preference and sensitivity are two most essential elements of food evaluation. Such criteria are not always constant and often change depending on internal states such as hunger and satiety. Recent evidences reveal that starvation induces increased sweet taste preference and sensitivity at the periphery and in the CNS in various species from fruit flies to humans [81, 126, 127]. Electrical recordings of various neurons in central brain areas in mice and monkeys including amygdala, orbital frontal cortex, and hypothalamus have indicated the existence of neurons that can respond to taste stimuli in a state (hunger/satiety)-dependent manner [128, 129, 130]. However, the key neuronal pathway(s) responsible for hunger-induced taste modification are still unknown.
Neuromodulators such as neurotransmitters, neuropeptides, and endocrine hormones, play an important role in changing the morphological and functional characteristics of neural circuits to achieve behavioural flexibility. The changes in taste preference could occur through variation in the peripheral taste receptor cells, or in higher order neural circuits controlling food intake in the brain. To understand how changes in the internal state influence behavioural decisions in flies, various neurons in the SEZ whose activity depends on starvation state have been identified. It has been suggested that Dopamine is a potent modulator of a variety of behaviors in mammals and flies. Tyrosine hydroxylase ventral unpaired medial (TH-VUM) dopaminergic neurons modulate feeding in response to nutritional needs (Figure 6A)  and feeding (
Role of various neuromodulators in regulating feeding responses in starved adult
Recent identification of second-order sweet taste neurons  has enabled investigations into the interplay between sweet taste circuits and other sweet- and starvation responsive neurons to understand the neural basis of feeding behavior. Both starvation state and an increase in dopamine signaling brings about an enhancement of sGPN sensitivity to sucrose. In both cases, increases in sucrose- induced calcium activity occurs in the absence of corresponding changes in peripheral sweet Gr5a+ neural activity. Other studies have detected that starvation leads to increases in sucrose-evoked electrophysiological [150, 151] or calcium activity in Gr5a+ taste neurons . In most cases, the observed increases in GRN sensitivity was comparatively small in magnitude compared with the alterations in
There are several other neurons that have been identified as modulating sugar feeding. A pair of
In another study, it has been shown that only sweet neurons express GABAB receptor (GABABR) . GABABR mediates presynaptic inhibition of calcium responses in sweet GRNs, and both sweet and bitter stimuli evoke GABAergic neuron activity in the vicinity of GRN axon terminals. Blockage of GABABR both lead to increased sugar responses and decreased suppression of the sweet response by bitter compounds. This study propose a model in which GABA acts via GABABR to expand the dynamic range of sweet GRNs through presynaptic gain control and suppress the output of sweet GRNs in the presence of opposing bitter stimuli .
Further evidences  show that
It has also been shown that starvation of amino acid stimulates yeast feeding by regulating central brain circuits. Two dopaminergic neurons (DA-WED) in each hemisphere of the adult brain innervating the “Wedge” neuropil are suggested to encode protein hunger. The suppression of these neurons results in decrement of yeast intake but elevates the sucrose consumption, whereas if these neurons are triggered they enhances the yeast intake but minimizes the sucrose consumption. Thus, like overall hunger and thirst, nutrient specific hunger motive may also compete for behavioral expression .
Mating has also been shown to be responsible for modifying the feeding behavior in female
It has been studied and shown that mushroom body controls the responses of adult flies to learned odours as well as regulates their innate food seeking behavior elicit by food odours. A study depicted that 5 of the 21 types of MBONs (Mushroom body output neurons) are required for starved flies to seek food odours. Four other MBONs (MBON-a3, MBON-b2b02a, MBON-a02 and MBON-g2a01) and their corresponding dopaminergic neurons (DANs) also regulate innate food seeking behavior. Obstructing MBONs and DANs reduce innate food seeking behavior in starved flies, and activation of dopaminergic neurons is sufficient to evoke food seeking behavior in fed flies. The results from RNAi knock-down of different receptors for various hunger and satiety cues illustrates that the MB innervating dopaminergic neurons are modulated by many of these signals, making the MB an integrative center for hunger and satiety signals in the fly brain .
11. Influence of taste on food intake and obesity in humans
High calories (especially overconsumption of energy from high fat and sugar foods) and low nutrition density (poor nutrition) are associated with many chronic metabolic diseases including cardiovascular diseases, obesity, diabetes mellitus type 2 and eating disorders in humans. It’s a great burden on healthcare system in any country and effective intervention strategies are yet to be found to control them. Past research has suggested that taste impacts the selection of food and its intake in animals as well as other factors like satiation and palatability. Obese and overweight individuals show a tendency of selecting energy-dense-food . In humans, pleasure achieved by food can stimulate “non- homoeostatic” eating making it a prospective player contributing obesity . Nonetheless, factors like previous food experiences, liking, wanting, taste sensitivities and depressed sense of taste cannot be ignored. Many pathways, neural circuits and neurohormones involved as discussed in
Although it has been seen that smell also plays a key role in modulating taste perception and influence food intake in individuals , but alteration in reward, dopamine signaling, homeostatic signals and affective circuits lead to hedonic eating causing obesity [162, 163]. Various neuroimaging methods have provided insights into central mechanisms underlying taste and hedonic eating highlighting the role of taste circuits in obesity. It has been found food stimuli causes different neural brain responses in obese individuals compared to normal weight people showing striking structural and functional brain circuitry alterations [164, 165, 166, 167, 168, 169, 170]. A recent review by  and others [172, 173] have beautifully described neural correlates of sweet, fat, umami, bitter, salty, and sour tastes across brain areas implicated in obesity. Although more conclusive neuroimaging outcomes are required to confirm the role of various taste neural circuits but experimental data indicates different hedonic responses to taste information in obesity. Dysregulations in brain reward circuitry in response to fat and sugar has been associated with obesity [165, 168, 174, 175, 176, 177] suggesting fat and sugar affect brain reward circuitry differently. Similarly, high salt consumption has been linked to obesity engaging different brain areas which modulate taste processing and reward [178, 179]. These brain circuits also encode salt taste intensity [178, 180]. Data showing convincing differences in higher salt sensitivities between obese and normal individuals is still insignificant [181, 182]. Studies on neural responses to salt taste in case of obesity are still limited.
Another taste studied in the context of obesity is Umami which contributes to a sense of satiety [183, 184]. Obese individuals show reduced sensitivity but higher preference for umami taste [185, 186] than healthy controls. Since, umami and salt taste both activate primary gustatory cortex circuits in case of umami high tasters compared to low tasters suggest that both tastes share common processing system and may contribute to feeding behaviors implicated in obesity in a similar manner . Bitter taste influence dietary fat consumption suggesting its relevance in obesity . Bitter taste linked with appetite reduction affect many brain areas [188, 189, 190]. Conditioning to bitter taste modulates Hedonic evaluation . Alterations in brain activation patters associated with bitter taste in individuals with obesity  compared to people without obesity have been observed but more consistent and reliable findings are needed to understand the interaction between brain responses and hedonic ratings of bitter taste [192, 193]. Sour taste is least explored in context of obesity but it plays major role in food selection and consumption and recruit brain regions in sex, age and internal state, condition dependent manner [194, 195]. Neural correlates of sour taste in obesity are limited and require further investigations. dysregulation of gut to brain neural connections and chemosensory pathways along this axis may also contribute to increased risk of obesity  suggesting gut could offer potential therapeutic targets in obesity . Nutritional interventions to target neural pathways involved in taste behaviors and perception could offer solutions for prevention and treating obesity in humans.
Further detailed neuroimaging studies to understand taste response, taste physiology and dietary intake in humans and higher animal model systems are required to illustrate the neurobiological underpinnings of taste modalities and their relevance in obesity. Further research to characterize the influence of gut taste receptors and neural circuits on brain responses following food consumption and its modulation by smell in obese individuals that influence food intake are also needed. Collectively, research on invertebrate model system like
For the animal fitness, feeding is regulated by peripheral and central feeding circuits to help in acquiring a necessary and balanced dietary input for energy and nutrient homeostasis. It is subjected to intense regulation by multiple neuromodulator systems. In this chapter, we have illustrated recent progress in understanding neural circuits and its modulation in the feeding behavior including local circuits and motor neurons of adult flies which links various internal energy and nutrient needs to adaptive behaviors. This chapter has integrated information about the structure, function, and molecular regulation of fly taste and feeding circuits. The fruit fly
Humans live in a society very different from the ones that shaped the evolution of our brains. Easy access to cheap, calorie-rich foods has resulted in widespread obesity and an explosion of obesity-related diseases such as type 2 diabetes, hypertension, and heart disease. A detailed understanding of how feeding behaviour is controlled at the level of neural circuits is an important step towards developing new ways to treat and prevent obesity. Humans consume more calories when their diets consist of processed foods . It has been shown that reducing taste sensation at the periphery, a high sugar diet impairs the central Dopamine processing of sensory signals and weakens satiation . Given the importance of sensory changes in initiating this cascade of circuit dysfunction, understanding how diet composition mechanistically affects taste is imperative to understand how the food environment directs feeding behavior and metabolic disease.
This work is supported by Wellcome trust/DBT India Alliance Fellowship (grant number IA/I/15/2/502074) awarded to PK.
Declaration of conflicting interests
The authors declares no potential conflicts of interest with respect to authorship and publication of this article.