Skip to content

Advertisement

Flavour

Review
Open Access

Beyond flavour to the gut and back

Flavour20154:37

https://doi.org/10.1186/s13411-015-0047-8

©  Kadohisa. 2015

Received: 24 September 2015

Accepted: 15 December 2015

Published: 29 December 2015

Abstract

This paper describes how food is sensed in both the mouth where it produces food reward and pleasantness that guides food intake and is sensed in the gut where it produces satiety and conditioned effects including learned appetite and learned satiety for the food eaten. Taste and other receptors present in both the mouth and gut are involved in these effects. The signals about the presence of food in the mouth and gut are transferred by separate pathways to the brain where the satiety signals from the gut reduce the reward value and subjective pleasantness of taste and other oral sensory signals including food texture. Food flavour preferences can be associatively conditioned by pairing with food in the gut in brain regions such as the orbitofrontal cortex and amygdala. Current issues considered in this paper are how gut sensing of food influences hormone release including cholecystokinin (CCK), peptide YY (PYY), and glucagon-like peptide-1 (GLP-1); how the sensing of different nutrients in the gut may influence unconditioned satiety and conditioned preference and satiety; and how cognition may modulate the pleasantness of food and thus the control of food intake.

Keywords

Food intakeTasteOral signalVisceral signalRewardSatiety

Review

Background

Food provides us with nutrition, energy, and reward with its subjective correlate of pleasure, and then satiety. Signals elicited by food in the mouth produce reward and pleasantness, while those in the gut produce satiety, but can also lead to a conditioned (learned) preference and/or a conditioned satiety for the orally sensed flavour. This paper reviews the taste and other sensing mechanisms in the mouth and the gut and shows how they contribute to these reward, satiety, and conditioned effects mediated by signals produced when food reaches the gut. Understanding these signals and their interactions in the brain provides an important foundation for understanding the control of food intake and its disorders in which hunger, satiety, and food reward signals may be altered.

Taste and other receptors for food in the mouth and gastrointestinal tract

Taste sensation is an important contributor to the reward value and delicious sensation produced by food in the mouth. In addition to taste, other oral sensory processes including oral texture contribute to the reward value of food flavour, as do olfactory, visual, and cognitive effects. At least five classes of oral taste receptor or sensors (T1R2 + T1R3 for sweet, sodium channel ENaC for salt, T2Rs for bitter, and PKD2L1-expressing TRC for sour, and T1R1 + T1R3 for umami) [1–6] sense food and transmit signals to the brain, with the rostral part of the nucleus of the solitary tract (NTS), the first synapse in the central nervous system. When taste reaches the brain, it, together with olfactory and visual inputs, can change the physiological state including the production of saliva and secretion of hormones [7–9]. These cephalic phase responses elicited by the sight, smell, and taste of food before ingestion are primarily mediated through the parasympathetic system to change physiological states and secretion of hormones such as insulin, ghrelin, and pancreatic polypeptide (PP) [7–9]. A palatable stimulus elicits greater cephalic PP release than a non-palatable stimulus [10], and cephalic PP release depends on the macronutrient [9]. It has been suggested that psychological and/or cognitive attitudes towards food can influence individual cephalic phase responses [10]. Recently, it has been reported that taste cells in the mouth express different types of peptides such as glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), and peptide YY (PYY) [11–13]. In rodents, these peptides may influence salt and sour sensitivity [14, 15]. In addition to taste, other oral sensing transmits information about food viscosity, fat texture, and temperature, as shown by the responses of neurons in the primary and secondary taste cortical areas [16–18].

When food enters the gastrointestinal (GI) tract, it activates a wide range of gut receptors, which stimulate locally the release of peptides such as CCK, PYY, ghrelin, and GLP-1 from endocrine cells [12, 19–24], which play a crucial role in the regulation of food intake [25–30]. Sugar or sweetener delivered into the GI tract acts through sodium-glucose transporters (SGLTs) to stimulate the release of GLP-1 [12, 31, 32]. In contrast, glucose transporter type2 (GLUT2) is not involved in the release of GLP-1 [12, 33, 34]. Activation of T2R bitter receptors in the GI tract can lead to the release of CCK or PYY, which can influence vagal afferents [19, 35, 36]. However, the role of gut taste receptors in releasing hormones is controversial. An artificial non-caloric sweetener, sucralose, does not induce the release of GLP-1 by affecting L cells in rats [37] and humans in vivo [38, 39], but it does induce the release of GLP-1 from mouse enteroendocrine cells in vitro [40]. Gut receptors for other nutrients such as amino acids and fatty acids have been identified. For example, GPRC6A and CaSR are receptors for amino acids and FFARs for free fatty acids including FFA2 (GRP43) and FFA3(GRP41) which are receptors for short-chain fatty acids (SCFAs) produced by the gut microbiome [12, 41–43]. These receptors are involved in the secretion of peptide hormones such as GLP-1, CCK, and PYY with contribution to energy metabolism [12, 41–43]. Thus, taste receptors in the gut will not alone be responsible for peptide hormone release and other receptors for amino acids and fatty acids, and transporters such as SGLTs are also involved in peptide hormone release. These peptide hormones may act both peripherally and centrally to influence processes in the gut and in the brain. Vagal afferents which project to the caudal part of the NTS convey information about some nutrients in the GI tract [44].

Intragastric administration of different taste solutions modulates blood-oxygen-level-dependent (BOLD) signals in different areas of the rat brain; for example, glucose modulates BOLD signals in the anterior cingulate cortex (ACC), insular cortex (IC), the ventral tegmental area (VTA), the substantia nigra (SN), and the amygdala, and umami modulates BOLD signals in the NTS, hypothalamus, and the amygdala [45, 46]. However, saccharin administration did not modulate BOLD signals in the VTA, SN, or amygdala in the same way as glucose [47].

Importantly, although taste receptors in the gut are implicated in peptide hormone release, they are not involved in taste sensation. The fact that patients who take a meal through a nasogastric or gastrostomy tube state that they do not taste and do not enjoy the food [48] provides evidence that gut taste receptors are not involved in taste sensation.

In summary, taste receptors in the mouth and GI tract have different roles in food intake (Fig. 1). Taste receptors in the mouth primarily mediate taste sensations which reflect properties of tastants, such as their intensity and reward value and pleasantness. Oral taste receptors are necessary for the full rewarding effects of sweet taste in that sucrose consumption is reduced in the T1R3 knockout mice [49]. Taste receptors and other receptors including chemoreceptors in the gut contribute to activating the endocrine system to release peptide hormones and also carry signals via vagal afferents to the brain. Understanding these gut food sensing mechanisms better may lead to better treatments for metabolic disease such as diabetes mellitus as well as disorders in food intake control.
Figure 1
Fig. 1

Taste receptors in the mouth and gastrointestinal tract. Taste receptors in the mouth primarily mediate taste sensations which reflect the intensity and palatability of the taste. Taste receptors in the gut contribute to unconditioned (unlearned) satiety, to conditioned satiety, and to conditioned appetite effects, by neural pathways from the gut to the brain and by activating hormones

Pathways of oral and visceral information

Neural pathways

Taste receptors in the mouth connect via the facial (cranial nerve VII), glossopharyngeal (cranial nerve IX), and vagus (cranial nerve X) nerves to the central nervous system (CNS). In parallel, other food properties such as temperature and texture are conveyed to the CNS via the trigeminal nerve (cranial nerve V). The vagus also innervates the GI tract. The NTS in the medulla is the first central relay for the primary sensory nerves [50]. Nerves V, VII, and IX which convey taste largely terminate in the rostral lateral segment of NTS, while vagal afferents (X) are much more concentrated in the caudal medial segment of the NTS [50]. After this, there are differences between primates and rodents. In the primate, the projections from the rostral, gustatory region of the NTS bypass the parabrachial nucleus (PBN) on their way to the thalamic gustatory relay in the caudal half of the parvicellular division of the ventroposteromedial nucleus (VPMpc). Then, gustatory information in the VPMpc is transferred to the granular IC [51, 52] which projects to the lateral and basal nuclei of the amygdala [53] and the orbitofrontal cortex (OFC) where visual and olfactory modalities converge with taste and oral texture [51, 52, 54–56]. In the rodent, the taste part of the NTS projects to the PBN [57] which projects to the VPMpc, the central nucleus of the amygdala (CEA), and to the hypothalamus [58, 59] (Fig. 2), and the PBN has reciprocal connections from the CEA and hypothalamus [60, 61].
Figure 2
Fig. 2

Taste pathways in the macaque and rat. In the macaque, gustatory information reaches the nucleus of the solitary tract (NTS), which projects directly to the taste thalamus (parvicellular division of the ventroposteromedial nucleus, VPMpc) which then projects to the taste cortex in the anterior insula (Insula). The insular taste cortex then projects to the orbitofrontal cortex (OFC) and amygdala (Amy). The OFC projects taste information to the anterior cingulate cortex (ACC). The OFC, ACC, and Amy project to the hypothalamus (HT). In macaques, feeding to normal self-induced satiety does not decrease the responses of taste neurons in the NTS or taste insula (and by inference not VPMpc). In the rat, in contrast, the NTS projects to a pontine taste area, the parabrachial nucleus (PBN). The PBN then has projections directly to a number of subcortical structures, including the HT and Amy, thus bypassing thalamo-cortical processing. The PBN in the rat then projects to the taste thalamus (VPMpc), which projects to the rat taste insula. The taste insula in the rat then projects to an agranular orbitofrontal cortex (AgOFC), which probably corresponds to the most posterior part of the primate OFC, which is agranular. (In primates, most of the OFC is granular cortex, and the rat may have no equivalent to this [210, 211] Fig. 2.1, see also 87 Fig. 1.1). In the rat, satiety signals such as gastric distension and satiety-related hormones decrease neuronal responses in the NTS (see text) and by inference therefore in the other brain areas with taste-related responses, as indicated in the figure. Adapted from ref. [89]

With respect to visceral afferent pathways (Fig. 3), the visceral region in the caudal part of the NTS projects to the PBN. The PBN projects to the rostral half of the VPMpc (the non-taste part), the CEA, the lateral hypothalamic nuclei, the VTA, and to the SN in macaques [52, 57, 62, 63]. The visceral part of VPMpc projects to the agranular insula which is located just posterior to the OFC [64, 65] and the insula projects to the ventral striatum (VS) [66]. The VTA and SN project to the VS, which also receives inputs from the OFC and ACC [67–70], which is part of a reward circuit [69] that could drive the motivation for eating.
Figure 3
Fig. 3

Visceral information pathways in the macaque. Visceral afferent information reaches the caudal part of the nucleus of the solitary tract (NTS), which projects to the parabrachial nucleus in the pons (PBN). The PBN projects to the Thalamus (the visceral not taste part of VPMpc, amygdala (Amy), hypothalamus (HT), and the ventral tegmental area (VTA). Visceral information from the Thalamus reaches the visceral part of the Insula, which in turn projects to the orbitofrontal cortex (OFC). The visceral information from the VTA, Amy, Insula, and OFC reaches the ventral striatum (VS). Taste information (not shown in the figure) reaches the taste insula, which projects to the OFC. In the OFC, both oral and visceral information is integrated, in that the responses of OFC taste neurons are decreased to zero by feeding to satiety, which reduces visceral and hormonal satiety signals. As a result of this integration in the OFC, the reward value of taste is represented in the OFC. The OFC projects to the Amy, HT, and the VS. In the ACC, actions are linked associatively with outcomes such as taste to implement actions to obtain goals such as rewards

Humoral pathway

Individual gut peptide hormonal signals which influence the regulation of food intake are transferred to the CNS in different ways: some peptide hormones such as CCK, PP, PYY, oxyntomodulin (OXM), and GLP-1 may act via effects mediated peripherally transmitted through the vagus, some like leptin are transferred via the bloodstream, and others like ghrelin transfers information via both neural and humoral pathways [71–76]. Peptide hormone signals via the bloodstream reach the arcuate nucleus (ARC) of the hypothalamus [71, 72, 74, 75, 77, 78].

Cortical and subcortical areas involved in processing of information from the mouth and gut

Insular cortex

A taste region of the granular anterior IC receives oral information from the VPMpc [51, 52] and is therefore by definition primary taste cortex. Insular taste cortex neurons discriminate not only between taste stimuli [55, 79–82] but also between other sensory modalities such as texture and temperature, which in some cases are combined with taste responsiveness by some single neurons [18]. The activity of primate IC neurons is not modulated by satiety [80, 83], and the same applies to primate NTS neurons [84]. In contrast, in rodents, satiety influences taste processing even in the NTS [85], making the system very different from that of primates, and implying that reward value or hedonics is not clearly separate from sensory processing in rodents [86–89] (Fig. 2). In rodents, the IC is involved in the learning of conditioned taste aversions (CTAs) [90–94].

There also appears to be a visceral representation in the agranular area of the IC, in the ventral part of the anterior IC [65], and the agranular insula projects to the VS [66]. Stimulation of the anterior IC elicits autonomic responses and modulation of vascular and respiratory states [95]. Thus, signals from the mouth and gut are processed separately within the primate IC.

Orbitofrontal cortex

The OFC receives gustatory information from the IC, and the posterior OFC has been recognised as an area which processes visceral and also olfactory and visual information about foods [16, 17, 55, 65, 96–104]. The OFC projects to the ACC, hypothalamus, amygdala, and VS [56, 64, 67–70, 103]. In addition, the OFC plays an important role in the reward value and the related subjective pleasantness of oral stimuli. First, OFC neurons discriminate between different visual stimuli which are associated with different rewards (such as foods) or punishers (such as the taste of salt) [100, 105–108]. Second, the responses of OFC neurons to taste, olfactory, and visual stimuli produced by food are decreased to zero after the reward value of the food has been decreased by feeding the food to satiety [109, 110]. Third, the activity of OFC neurons reflects the reward value of visual and olfactory stimuli, for the neuronal responses reverse when the association of the visual and olfactory stimuli with taste reward or punishment reverses [100, 111]. That is, the OFC updates stimulus value rapidly when it changes [87, 88]. Stimulation of the posterior OFC elicits vascular and respiratory responses [95, 112, 113].

Anterior cingulate cortex

Areas 24, 25, and 32 of the ACC (in the rat the infralimbic cortex and prelimbic area are counterparts of areas 25 and 32) receive inputs from the OFC [64, 114]. Areas 24, 25, and 32 project to the VS [70], and areas 25 and 32 project to the hypothalamus [103, 115, 116]. Neurons of areas 25 and 32 or the infralimbic cortex encode taste stimuli [117, 118] and in rodents show more sustained responses to palatable taste stimuli compared to IC neurons [118]. Neuronal activity in areas 25 and 32 is modulated by internal information such as thirst [119] and in area 24 is related to reward-related actions [120, 121]. There is preliminary evidence that the responses of ACC neurons to taste stimuli are influenced by feeding to satiety [117]. In addition, stimulation of the ACC produces vascular and respiratory responses [122, 123]. Primate lesion studies suggest that the ACC is a site of action-outcome learning, where the outcome is a reward such as taste [124].

Amygdala

The CEA receives visceral information directly from the PBN [52, 57, 62, 63, 125, 126] and gustatory information from the posterior OFC [56, 127] while the lateral nucleus of the amygdala (BLA) receives gustatory information from the IC [128, 129]. There are some connections between the CEA and BLA [130]. The CEA and BLA project to the VS [131]. Amygdala neurons are broadly tuned across taste and other oral sensory stimuli compared to the OFC and IC neurons [132, 133]. The amygdala is involved in associative learning, with the BLA involved in the formation of Pavlovian incentives involving the association of a conditioned stimulus (CS) with the specific sensory features of the unconditioned stimulus (US). By contrast, the CEA is involved in preparatory conditioning—that is, in the association of a CS with the general affective properties of the US [134, 135]. Taking account of information processed from the mouth and GI tract, the BLA may reflect signals elicited by food in the mouth while the CEA may reflect those in the GI tract. The responses of neurons of the CEA and BLA in rats to conditioned taste stimuli are influenced by the conditioning [136]. Amygdala neurons of primates discriminate visual stimuli associated with a positive (sweet taste) or negative (air puff or tail pinch) outcome [137, 138], but do not reverse their firing rapidly when the reward contingency changes [139], and are thus unlike OFC neurons. In addition, the amygdala is involved in the evaluation of food reward during the period of selective satiation in that the devaluation is impaired by inactivating the BLA before the selective satiation, but not after satiation [140]. The responses to taste of some CEA neurons in primates showed relatively small decreases, on average by 58 %, during satiety [141].

Hypothalamus

The hypothalamus receives neural inputs from different areas such as the PBN, amygdala, and the prefrontal cortex including the anterior IC, caudal OFC, and the ACC [52, 57, 63, 103, 115, 116, 126], and gut peptide hormone signals via a humoral pathway [71, 72, 74, 75, 77, 78]. The hypothalamus projects to the OFC [56, 142–144]. The hypothalamic nuclei, including the ARC where neural and humoral signals communicate, the lateral hypothalamic area, ventromedial hypothalamic nucleus, and the paraventricular nucleus are key regions for food intake control ([72, 74, 75, 77, 78]. The ARC contains agouti-related peptide-expressing neurons and pro-opiomelanocortin neurons which have positive and negative effects on feeding behaviour, respectively [74, 75, 145–147]. The ARC communicates with the paraventricular nucleus, lateral hypothalamic area, and ventromedial hypothalamic nucleus [72, 74, 75, 77, 78, 146, 147]. It is noted that rat hypothalamic neurons which express SGLTs respond to changes in glucose concentration [31, 148]. In addition, the responses of lateral hypothalamic area neurons to a taste stimulus and to the sight of food decrease to zero when the food is fed to satiety [149, 150] in a similar way to that of OFC neurons which may provide the relevant taste and visual inputs to the hypothalamus. Thus, the hypothalamus reflects the integration of sensory inputs produced by food with unconditioned and probably conditioned satiety signals of neural and humoral origins.

In summary, oral and visceral signals are transferred to the cortices via the thalamus in the primate. The IC is involved in the discrimination of oral sensory stimuli. In rodents, the IC may contribute to conditioned taste aversion. The OFC integrates individual sensory modalities of food (taste, olfactory, visual, oral texture, and temperature) to provide a multimodal representation of food and represents it in terms of its reward value. The ACC is implicated in action-outcome learning, that is, of which actions are associated with reward. The OFC and ACC project to the VS which also receives visceral- and emotion-related information from the agranular insula and amygdala, respectively, which takes part in a reward circuit. The amygdala and hypothalamus receive visceral inputs from the PBN directly as well as sensory inputs from these cortical areas. The OFC and amygdala are involved in learning associations of visual and olfactory stimuli with taste and will act together to influence feeding behaviour based on reward value [88, 151, 152]. The hypothalamus receives gut peptide hormonal signals and integrates these with neural information from the mouth and GI tract. Thus, in the primate, food-related signals from the mouth and gut are processed differently in separate areas and are integrated in the OFC and hypothalamus which are part of a reward circuit which drives goal-directed behaviours including food intake.

Human imaging studies including cognitive effects on food reward and GI function

Human imaging studies have shown taste-related activity in the IC, OFC, and in the ACC [153, 154]. Activations in a ventral part of the IC are related to autonomic signals [155] and the region may even overlap partly with the taste-responsive areas.

OFC BOLD signals represent the reward value and subjective pleasantness of taste as shown for example by taste devaluation by feeding to satiety [156–159] and are modulated by gut peptides, PYY, and ghrelin [160, 161]. The fact that the OFC and ACC show strong effects of cognitive labels and selective attention instruction that influence the palatability of taste and flavour indicates that the OFC and ACC are involved in the processes by which cognitive information modulates the pleasantness of flavour [162, 163]. In addition, the ACC plays a role in action-outcome learning [155, 164–167] to allow actions to be learned to obtain rewards. Thus, the orbitofrontal cortex and cingulate cortex contribute to control feeding behaviour by representing reward value including the effects of cognition and attention on reward value.

With respect to cognitive effect on GI function, it has been found, for example, that cognitive manipulation can modulate gut response such as gastric emptying [168] and affect subsequent food intake [169, 170]. Further investigation of how cognition affects food reward and GI function will be useful in developing our understanding of the control of food intake.

Interactions between oral and visceral sensory signals

Oral signals of taste, texture, and temperature, and retronasally sensed olfactory effects, implement the hedonic reward value of food, with subjective pleasantness correlated with activations in the OFC and ACC. Animals including humans work to obtain small quantities of these oral signals. Food placed directly into the gut or provided intravenously does not produce immediate unconditioned reward with small quantities [171, 172], though conditioning to food placed in the gut can be acquired in what is a form of learned appetite [173], sometimes referred to as appetition [174]. When ingested food reaches the GI tract, it produces satiety by producing gastric distension (as shown by the absence of satiety in sham feeding when food drains from a gastric or duodenal cannula [175, 176]), and the gastric distension only occurs if food enters the duodenum where it activates gut receptors so causing closing of the pyloric sphincter. If the distension is reduced at the end of a meal, then feeding resumes very quickly in non-human primates [176]. This is probably an unconditioned satiety effect produced by gastric distension. In addition to unconditioned effects of food in the gut, there are also conditioned effects whereby the post-ingestive consequences of a flavour can influence the reward value of the flavour later, as described below.

Sensory-specific satiety is the state in which a food becomes less rewarding after it has been eaten to satiety, but other foods may remain rewarding [87, 177, 178]. This phenomenon is implemented in the OFC [110], which receives not only sensory but also visceral information [55, 65, 97–99, 102, 103]. Further integration of all these signals may occur in the hypothalamus which receives projections from the OFC and PBN.

CTAs which involve associative learning between oral and visceral stimuli have been shown with rats [179–185]. For example, a novel taste solution (CS) followed by aversive malaise (US) will not be ingested afterward although the taste solution was rewarding before the conditioning. The acquisition of this conditioning depends on the IC in rats, but changes then occur in the NTS (which will influence activity in all rodent taste areas), and the CTA thereafter no longer requires the presence of the IC [93, 94]. CTAs have rarely been studied with non-human primates. Conditioned taste preferences (CTPs) depend on visceral signals, involving calories and nutrients that are components of the unconditioned stimulus [173, 184–186]. The conditioning can be fast, apparently influencing preference for a flavour stimulus such as cherry vs grape within 15 min [174, 187]. The post-oral effect apparently does not require T1R2 + T1R3 sweet taste receptors in the gut in that flavour preference was still conditioned to intragastric infusion of sucrose in T1R3 knockout mice [188]. A humoral pathway is involved in post-oral glucose conditioning since visceral deafferentiation does not impair glucose-conditioned flavour preferences [189]. In addition, humoral signals generated by intestinal SGLT1 and SGLT3, and to a lesser degree, GLUT2, may mediate post-oral sugar appetition in mice [190]. It has been suggested that sugar metabolism is not essential for the post-oral intake-stimulating and preference-conditioning actions of sugars in mice [190–193]. Interestingly, non-deprived and sated animals can still acquire strong conditioned taste preferences [194].

The energy value of food can produce conditioned appetite or preference for a food and can also produce conditioned satiety [173]. Most of the above studies have been on conditioned preference produced by food in the GI tract. It will be of interest in future research to analyse in addition how post-ingestive signals can produce conditioned satiety for the flavour with which they are paired. It would be of interest to develop our understanding of conditioned satiety, for this may be relevant to food intake control and its disorders. There is some evidence on this in humans below.

Sensory-specific satiety and associative learning in humans

Interestingly, there is no significant difference between sensory-specific satiety following high- and low- caloric sweetened food [195]. The OFC BOLD signal produced by the flavour of food is decreased in a sensory-specific satiety way by the food eaten to satiety, and this reduction of the BOLD signal in the OFC is correlated with the reduction of subjective pleasantness of the food eaten to satiety [159, 196]. The BOLD signals in the OFC and amygdala produced by visual stimuli associated with food are reduced after that food is fed to satiety [197].

CTAs have been described in humans [183, 198], in which the subjects describe feeling nausea after taking some food or drink and then decreased ingestion of the substances. In laboratory studies, subjects who have been exposed to unfamiliar flavoured food or drink (the conditioned stimulus) and are then rotated to cause motion sickness (the unconditioned stimulus) show less ingestion of the flavoured food or drink afterwards [199, 200]. CTPs are likely to be acquired depending on physiological state, such as a deficit in a particular nutrient, e.g., protein [201], or in energy [202]. Young children show preferences for high-caloric flavour after experiences of unfamiliar-flavoured foods with low- and high-energy density suggesting that they learn post-ingestive consequences of caloric density [203, 204]. Interestingly, umami flavour (monosodium glutamate) reduces hunger and enhances satiety [205, 206], which suggests that umami may produce conditioned satiety and act as a potential regulator of food intake. Thus, both learned appetite and learned satiety can result from an association between the flavour of a food and its post-ingestive consequences [173, 207] where the integrated information about that food will be transferred into a reward circuit to drive feeding behaviour.

Taken together with animal studies, preferences and aversions to food can be conditioned by food in the GI tract where the OFC and amygdala can play an important role in associative learning between oral and gut information with the hypothalamus involved in the integration of humoral and neural signals such as hunger and satiety. To help control feeding behaviour better, it is crucial to understand the mechanisms that produce signals for nutrient deficits and/or physiologically required energy, and those that produce satiety signals, and how these are integrated in the brain and combined with cognitive signals in which the OFC and ACC are involved. This is likely to lead to advances in the treatment of eating disorders such as anorexia nervosa where it has been reported that the bottom-up processing is decreased while the top-down cognitive processing is increased [208, 209].

Conclusions

Food is sensed twice, first in the mouth and then in the gut. The signals are transferred separately to the central nervous system through different pathways and interact in areas such as the orbitofrontal cortex and hypothalamus in primates to produce reward signals that influence food intake and that are reflected in the subjective pleasantness of taste, flavour, and food. The rewarding effect of food produced by food in the mouth is decreased by feeding to satiety and can also be influenced by learning by signals in the gut that lead to conditioned appetite and satiety for the flavour of the food. The amygdala and orbitofrontal cortex are involved in reward evaluations and conditioned preference and aversion. The effects of cognition and attention on taste and flavour are evident in the orbitofrontal cortex and anterior cingulate cortex.

The signals that originate in the mouth are a major contributor to the reward value of food, which can lead to a decision to eat that food. Signals that originate in the gut are involved in the termination of a meal, that is, in satiety. Gut signals which are transferred via neural and humoral pathways can provide information about the metabolic and nutritional content of the food that can lead, over time, to learned appetite and satiety for the flavour of a food and influence reward value of foods. The extent to which these gut signals mediate nutrient-specific effects on food intake is an important subject for future research. In addition, one key area for investigation is how the hunger and satiety signals represented in the hypothalamus modulate taste, olfactory, and flavour signals to produce a food reward signal that drives eating. Little is known for example about how these hunger and satiety signals project to reward-related areas such as the orbitofrontal cortex. Understanding further the dual sensing of food in the mouth and gut, and cognitive signals, is important for a better understanding of the control of food intake and potentially of its disorders and metabolic disorders. Identifying the neural processing of sensory signals produced by chemical components of food may lead to promising treatments for metabolic disorders, and understanding top-down cognitive processes may contribute to improve treatment for eating disorders.

Abbreviations

ACC: anterior cingulate cortex, ARC: arcuate nucleus, BLA: basolateral nucleus of the amygdala, BOLD: blood-oxygen-level-dependent, CEA: central nucleus of the amygdala, CKK: cholecystokinin, CNS: central nervous system, CS; conditioned stimulus, CTA: conditioned taste aversion, CTP: conditioned taste preference, GI: gastrointestinal, GLP-1: glucagon-like peptide-1, GLUT2: glucose transporter type2, IC: insular cortex, NTS: nucleus of the solitary tract, OFC: orbitofrontal cortex, PBN: parabrachial nucleus, PP: pancreatic peptide, PYY: peptide YY, SGLT: sodium-glucose transporter, US: unconditioned stimulus, VPMpc: parvicellular division of the ventroposteromedial nucleus, VS: ventral striatum.

In addition, a short glossary of some of the terms used follows:

Pleasure is a subjective sensation. Pleasantness describes how much pleasure is produced by a stimulus. A reward is a stimulus for which an instrumental action will be performed. Delicious sensation is a sensation produced by a delicious flavour, and implies the Japanese word umami which translates as delicious. Reward value is an operationally measure by how hard an animal will work to obtain a reward, and by the preference for that reward compared to other rewards. Subjective pleasantness refers to the subjectively reported pleasantness of a stimulus.

Declarations

Acknowledgements

This work was supported by MRC intramural programme MC-A060-5PQ10.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
MRC Cognition and Brain Sciences Unit, Cambridge, UK
(2)
Department of Experimental Psychology, University of Oxford, Oxford, UK

References

  1. Adler E, Hoon MA, Mueller KL, Chandrashekar J, Ryba NJ, Zuker CS. A novel family of mammalian taste receptors. Cell. 2000;100(6):693–702.PubMedView ArticleGoogle Scholar
  2. Nelson G, Chandrashekar J, Hoon MA, Feng L, Zhao G, Ryba NJ, et al. An amino-acid taste receptor. Nature. 2002;416(6877):199–202. doi:10.1038/nature726.PubMedView ArticleGoogle Scholar
  3. Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS. Mammalian sweet taste receptors. Cell. 2001;106(3):381–90.PubMedView ArticleGoogle Scholar
  4. Margolskee RF. Molecular mechanisms of bitter and sweet taste transduction. J Biol Chem. 2002;277(1):1–4. doi:10.1074/jbc.R100054200.PubMedView ArticleGoogle Scholar
  5. Roper SD, Chaudhari N. Processing umami and other tastes in mammalian taste buds. Ann N Y Acad Sci. 2009;1170:60–5. doi:10.1111/j.1749-6632.2009.04107.x.PubMedPubMed CentralView ArticleGoogle Scholar
  6. Yarmolinsky DA, Zuker CS, Ryba NJ. Common sense about taste: from mammals to insects. Cell. 2009;139(2):234–44. doi:10.1016/j.cell.2009.10.001.PubMedPubMed CentralView ArticleGoogle Scholar
  7. Mattes RD. Physiologic responses to sensory stimulation by food: nutritional implications. J Am Diet Assoc. 1997;97(4):406–13. doi:10.1016/S0002-8223(97)00101-6.PubMedView ArticleGoogle Scholar
  8. Power ML, Schulkin J. Anticipatory physiological regulation in feeding biology: cephalic phase responses. Appetite. 2008;50(2–3):194–206. doi:10.1016/j.appet.2007.10.006.PubMedPubMed CentralView ArticleGoogle Scholar
  9. Smeets PA, Erkner A, de Graaf C. Cephalic phase responses and appetite. Nutr Rev. 2010;68(11):643–55. doi:10.1111/j.1753-4887.2010.00334.x.PubMedView ArticleGoogle Scholar
  10. Teff K. Nutritional implications of the cephalic-phase reflexes: endocrine responses. Appetite. 2000;34(2):206–13. doi:10.1006/appe.1999.0282.PubMedView ArticleGoogle Scholar
  11. Kokrashvili Z, Yee KK, Ilegems E, Iwatsuki K, Li Y, Mosinger B, et al. Endocrine taste cells. Br J Nutr. 2014;111 Suppl 1:S23–9. doi:10.1017/S0007114513002262.PubMedPubMed CentralView ArticleGoogle Scholar
  12. Depoortere I. Taste receptors of the gut: emerging roles in health and disease. Gut. 2014;63(1):179–90. doi:10.1136/gutjnl-2013-305112.PubMedView ArticleGoogle Scholar
  13. Dotson CD, Geraedts MC, Munger SD. Peptide regulators of peripheral taste function. Semin Cell Dev Biol. 2013;24(3):232–9. doi:10.1016/j.semcdb.2013.01.004.PubMedPubMed CentralView ArticleGoogle Scholar
  14. Shin YK, Martin B, Golden E, Dotson CD, Maudsley S, Kim W, et al. Modulation of taste sensitivity by GLP-1 signaling. J Neurochem. 2008;106(1):455–63. doi:10.1111/j.1471-4159.2008.05397.x.PubMedPubMed CentralView ArticleGoogle Scholar
  15. Shin YK, Martin B, Kim W, White CM, Ji S, Sun Y, et al. Ghrelin is produced in taste cells and ghrelin receptor null mice show reduced taste responsivity to salty (NaCl) and sour (citric acid) tastants. PLoS One. 2010;5(9):e12729. doi:10.1371/journal.pone.0012729.PubMedPubMed CentralView ArticleGoogle Scholar
  16. Kadohisa M, Rolls ET, Verhagen JV. Orbitofrontal cortex: neuronal representation of oral temperature and capsaicin in addition to taste and texture. Neuroscience. 2004;127(1):207–21. doi:10.1016/j.neuroscience.2004.04.037.PubMedView ArticleGoogle Scholar
  17. Rolls ET, Verhagen JV, Kadohisa M. Representations of the texture of food in the primate orbitofrontal cortex: neurons responding to viscosity, grittiness, and capsaicin. J Neurophysiol. 2003;90(6):3711–24. doi:10.1152/jn.00515.2003.PubMedView ArticleGoogle Scholar
  18. Verhagen JV, Kadohisa M, Rolls ET. Primate insular/opercular taste cortex: neuronal representations of the viscosity, fat texture, grittiness, temperature, and taste of foods. J Neurophysiol. 2004;92(3):1685–99. doi:10.1152/jn.00321.2004.PubMedView ArticleGoogle Scholar
  19. Hao S, Sternini C, Raybould HE. Role of CCK1 and Y2 receptors in activation of hindbrain neurons induced by intragastric administration of bitter taste receptor ligands. Am J Physiol Regul Integr Comp Physiol. 2008;294(1):R33–8. doi:10.1152/ajpregu.00675.2007.PubMedView ArticleGoogle Scholar
  20. Kokrashvili Z, Mosinger B, Margolskee RF. T1r3 and alpha-gustducin in gut regulate secretion of glucagon-like peptide-1. Ann N Y Acad Sci. 2009;1170:91–4. doi:10.1111/j.1749-6632.2009.04485.x.PubMedView ArticleGoogle Scholar
  21. Kokrashvili Z, Mosinger B, Margolskee RF. Taste signaling elements expressed in gut enteroendocrine cells regulate nutrient-responsive secretion of gut hormones. Am J Clin Nutr. 2009;90(3):822S–5S. doi:10.3945/ajcn.2009.27462T.PubMedPubMed CentralView ArticleGoogle Scholar
  22. Chen MC, Wu SV, Reeve Jr JR, Rozengurt E. Bitter stimuli induce Ca2+ signaling and CCK release in enteroendocrine STC-1 cells: role of L-type voltage-sensitive Ca2+ channels. Am J Physiol Cell Physiol. 2006;291(4):C726–39. doi:10.1152/ajpcell.00003.2006.PubMedView ArticleGoogle Scholar
  23. Janssen S, Laermans J, Verhulst PJ, Thijs T, Tack J, Depoortere I. Bitter taste receptors and alpha-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying. Proc Natl Acad Sci U S A. 2011;108(5):2094–9. doi:10.1073/pnas.1011508108.PubMedPubMed CentralView ArticleGoogle Scholar
  24. Jang HJ, Kokrashvili Z, Theodorakis MJ, Carlson OD, Kim BJ, Zhou J, et al. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci U S A. 2007;104(38):15069–74. doi:10.1073/pnas.0706890104.PubMedPubMed CentralView ArticleGoogle Scholar
  25. Blackshaw LA, Grundy D. Effects of cholecystokinin (CCK-8) on two classes of gastroduodenal vagal afferent fibre. J Auton Nerv Syst. 1990;31(3):191–201.PubMedView ArticleGoogle Scholar
  26. Hewson G, Leighton GE, Hill RG, Hughes J. The cholecystokinin receptor antagonist L364,718 increases food intake in the rat by attenuation of the action of endogenous cholecystokinin. Br J Pharmacol. 1988;93(1):79–84.PubMedPubMed CentralView ArticleGoogle Scholar
  27. Raybould HE, Gayton RJ, Dockray GJ. CNS effects of circulating CCK8: involvement of brainstem neurones responding to gastric distension. Brain Res. 1985;342(1):187–90.PubMedView ArticleGoogle Scholar
  28. Batterham RL, Bloom SR. The gut hormone peptide YY regulates appetite. Ann N Y Acad Sci. 2003;994:162–8.PubMedView ArticleGoogle Scholar
  29. McGowan BM, Bloom SR. Peptide YY and appetite control. Curr Opin Pharmacol. 2004;4(6):583–8. doi:10.1016/j.coph.2004.06.007.PubMedView ArticleGoogle Scholar
  30. Wren AM, Small CJ, Ward HL, Murphy KG, Dakin CL, Taheri S, et al. The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology. 2000;141(11):4325–8. doi:10.1210/endo.141.11.7873.PubMedView ArticleGoogle Scholar
  31. Wright EM, Loo DD, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev. 2011;91(2):733–94. doi:10.1152/physrev.00055.2009.PubMedView ArticleGoogle Scholar
  32. Raybould HE. Gut chemosensing: interactions between gut endocrine cells and visceral afferents. Auton Neurosci. 2010;153(1–2):41–6. doi:10.1016/j.autneu.2009.07.007.PubMedPubMed CentralView ArticleGoogle Scholar
  33. Kellett GL, Brot-Laroche E, Mace OJ, Leturque A. Sugar absorption in the intestine: the role of GLUT2. Annu Rev Nutr. 2008;28:35–54. doi:10.1146/annurev.nutr.28.061807.155518.PubMedView ArticleGoogle Scholar
  34. Roder PV, Geillinger KE, Zietek TS, Thorens B, Koepsell H, Daniel H. The role of SGLT1 and GLUT2 in intestinal glucose transport and sensing. PLoS One. 2014;9(2):e89977. doi:10.1371/journal.pone.0089977.PubMedPubMed CentralView ArticleGoogle Scholar
  35. Behrens M, Meyerhof W. Gustatory and extragustatory functions of mammalian taste receptors. Physiol Behav. 2011;105(1):4–13. doi:10.1016/j.physbeh.2011.02.010.PubMedView ArticleGoogle Scholar
  36. Green BG. Chemesthesis and the chemical senses as components of a "chemofensor complex". Chem Senses. 2012;37(3):201–6. doi:10.1093/chemse/bjr119.PubMedPubMed CentralView ArticleGoogle Scholar
  37. Fujita Y, Wideman RD, Speck M, Asadi A, King DS, Webber TD, et al. Incretin release from gut is acutely enhanced by sugar but not by sweeteners in vivo. Am J Physiol Endocrinol Metab. 2009;296(3):E473–9. doi:10.1152/ajpendo.90636.2008.PubMedView ArticleGoogle Scholar
  38. Ma J, Bellon M, Wishart JM, Young R, Blackshaw LA, Jones KL, et al. Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects. Am J Physiol Gastrointest Liver Physiol. 2009;296(4):G735–9. doi:10.1152/ajpgi.90708.2008.PubMedPubMed CentralView ArticleGoogle Scholar
  39. Ford HE, Peters V, Martin NM, Sleeth ML, Ghatei MA, Frost GS, et al. Effects of oral ingestion of sucralose on gut hormone response and appetite in healthy normal-weight subjects. Eur J Clin Nutr. 2011;65(4):508–13. doi:10.1038/ejcn.2010.291.PubMedView ArticleGoogle Scholar
  40. Margolskee RF, Dyer J, Kokrashvili Z, Salmon KS, Ilegems E, Daly K, et al. T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1. Proc Natl Acad Sci U S A. 2007;104(38):15075–80. doi:10.1073/pnas.0706678104.PubMedPubMed CentralView ArticleGoogle Scholar
  41. Berthoud HR. Vagal and hormonal gut-brain communication: from satiation to satisfaction. Neurogastroenterol Motil. 2008;20 Suppl 1:64–72. doi:10.1111/j.1365-2982.2008.01104.x.PubMedPubMed CentralView ArticleGoogle Scholar
  42. Rasoamanana R, Darcel N, Fromentin G, Tome D. Nutrient sensing and signalling by the gut. Proc Nutr Soc. 2012;71(4):446–55. doi:10.1017/S0029665112000110.PubMedView ArticleGoogle Scholar
  43. Hara T, Kashihara D, Ichimura A, Kimura I, Tsujimoto G, Hirasawa A. Role of free fatty acid receptors in the regulation of energy metabolism. Biochim Biophys Acta. 2014;1841(9):1292–300. doi:10.1016/j.bbalip.2014.06.002.PubMedView ArticleGoogle Scholar
  44. Niijima A. Nervous regulation of metabolism. Prog Neurobiol. 1989;33(2):135–47.PubMedView ArticleGoogle Scholar
  45. Tsurugizawa T, Uematsu A, Uneyama H, Torii K. Different BOLD responses to intragastric load of L-glutamate and inosine monophosphate in conscious rats. Chem Senses. 2011;36(2):169–76. doi:10.1093/chemse/bjq107.PubMedView ArticleGoogle Scholar
  46. Tsurugizawa T, Kondoh T, Torii K. Forebrain activation induced by postoral nutritive substances in rats. Neuroreport. 2008;19(11):1111–5. doi:10.1097/WNR.0b013e328307c414.PubMedView ArticleGoogle Scholar
  47. Tsurugizawa T, Uneyama H. Differences in BOLD responses to intragastrically infused glucose and saccharin in rats. Chem Senses. 2014;39(8):683–91. doi:10.1093/chemse/bju040.PubMedView ArticleGoogle Scholar
  48. Tomita S, Terao Y, Hatano T, Nishimura R. Subtotal glossectomy preserving half the tongue base prevents taste disorder in patients with tongue cancer. International journal of oral and maxillofacial surgery. 2014. doi:10.1016/j.ijom.2014.02.006
  49. Sclafani A, Marambaud P, Ackroff K. Sucrose-conditioned flavor preferences in sweet ageusic T1r3 and Calhm1 knockout mice. Physiol Behav. 2014;126:25–9. doi:10.1016/j.physbeh.2013.12.003.PubMedPubMed CentralView ArticleGoogle Scholar
  50. Beckstead RM, Norgren R. An autoradiographic examination of the central distribution of the trigeminal, facial, glossopharyngeal, and vagal nerves in the monkey. J Comp Neurol. 1979;184(3):455–72. doi:10.1002/cne.901840303.PubMedView ArticleGoogle Scholar
  51. Pritchard TC, Hamilton RB, Morse JR, Norgren R. Projections of thalamic gustatory and lingual areas in the monkey, Macaca fascicularis. J Comp Neurol. 1986;244(2):213–28. doi:10.1002/cne.902440208.PubMedView ArticleGoogle Scholar
  52. Pritchard TC. Gustatory system. In: Mai JK, Paxinos G, editors. The Human Nervous System. Thirdth ed. MA: Elservier; 2011. p. 1187–218.Google Scholar
  53. Turner BH, Mishkin M, Knapp M. Organization of the amygdalopetal projections from modality-specific cortical association areas in the monkey. J Comp Neurol. 1980;191(4):515–43. doi:10.1002/cne.901910402.PubMedView ArticleGoogle Scholar
  54. Mufson EJ, Mesulam MM. Insula of the old world monkey. II: afferent cortical input and comments on the claustrum. J Comp Neurol. 1982;212(1):23–37. doi:10.1002/cne.902120103.PubMedView ArticleGoogle Scholar
  55. Rolls ET, Baylis LL. Gustatory, olfactory, and visual convergence within the primate orbitofrontal cortex. J Neurosci. 1994;14(9):5437–52.PubMedGoogle Scholar
  56. Carmichael ST, Price JL. Limbic connections of the orbital and medial prefrontal cortex in macaque monkeys. J Comp Neurol. 1995;363(4):615–41. doi:10.1002/cne.903630408.PubMedView ArticleGoogle Scholar
  57. Beckstead RM, Morse JR, Norgren R. The nucleus of the solitary tract in the monkey: projections to the thalamus and brain stem nuclei. J Comp Neurol. 1980;190(2):259–82. doi:10.1002/cne.901900205.PubMedView ArticleGoogle Scholar
  58. Norgren R. Taste pathways to hypothalamus and amygdala. J Comp Neurol. 1976;166(1):17–30. doi:10.1002/cne.901660103.PubMedView ArticleGoogle Scholar
  59. Lundy Jr RF, Norgren R. Pontine gustatory activity is altered by electrical stimulation in the central nucleus of the amygdala. J Neurophysiol. 2001;85(2):770–83.PubMedGoogle Scholar
  60. Li CS, Cho YK, Smith DV. Modulation of parabrachial taste neurons by electrical and chemical stimulation of the lateral hypothalamus and amygdala. J Neurophysiol. 2005;93(3):1183–96. doi:10.1152/jn.00828.2004.PubMedView ArticleGoogle Scholar
  61. Lundy Jr RF, Norgren R. Activity in the hypothalamus, amygdala, and cortex generates bilateral and convergent modulation of pontine gustatory neurons. J Neurophysiol. 2004;91(3):1143–57. doi:10.1152/jn.00840.2003.PubMedView ArticleGoogle Scholar
  62. Norita M, Kawamura K. Subcortical afferents to the monkey amygdala: an HRP study. Brain Res. 1980;190(1):225–30.PubMedView ArticleGoogle Scholar
  63. Pritchard TC, Hamilton RB, Norgren R. Projections of the parabrachial nucleus in the old world monkey. Exp Neurol. 2000;165(1):101–17. doi:10.1006/exnr.2000.7450.PubMedView ArticleGoogle Scholar
  64. Carmichael ST, Price JL. Connectional networks within the orbital and medial prefrontal cortex of macaque monkeys. J Comp Neurol. 1996;371(2):179–207. doi:10.1002/(SICI)1096-9861(19960722)371:2<179::AID-CNE1>3.0.CO;2-#.PubMedView ArticleGoogle Scholar
  65. Carmichael ST, Price JL. Sensory and premotor connections of the orbital and medial prefrontal cortex of macaque monkeys. J Comp Neurol. 1995;363(4):642–64. doi:10.1002/cne.903630409.PubMedView ArticleGoogle Scholar
  66. Chikama M, McFarland NR, Amaral DG, Haber SN. Insular cortical projections to functional regions of the striatum correlate with cortical cytoarchitectonic organization in the primate. J Neurosci. 1997;17(24):9686–705.PubMedGoogle Scholar
  67. Haber SN, Kunishio K, Mizobuchi M, Lynd-Balta E. The orbital and medial prefrontal circuit through the primate basal ganglia. J Neurosci. 1995;15(7 Pt 1):4851–67.PubMedGoogle Scholar
  68. Selemon LD, Goldman-Rakic PS. Longitudinal topography and interdigitation of corticostriatal projections in the rhesus monkey. J Neurosci. 1985;5(3):776–94.PubMedGoogle Scholar
  69. Haber SN, Knutson B. The reward circuit: linking primate anatomy and human imaging. Neuropsychopharmacology. 2010;35(1):4–26. doi:10.1038/npp.2009.129.PubMedPubMed CentralView ArticleGoogle Scholar
  70. Haber SN, Kim KS, Mailly P, Calzavara R. Reward-related cortical inputs define a large striatal region in primates that interface with associative cortical connections, providing a substrate for incentive-based learning. J Neurosci. 2006;26(32):8368–76. doi:10.1523/JNEUROSCI.0271-06.2006.PubMedView ArticleGoogle Scholar
  71. Huda MS, Wilding JP, Pinkney JH. Gut peptides and the regulation of appetite. Obes Rev. 2006;7(2):163–82. doi:10.1111/j.1467-789X.2006.00245.x.PubMedView ArticleGoogle Scholar
  72. Kalra SP, Dube MG, Pu S, Xu B, Horvath TL, Kalra PS. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr Rev. 1999;20(1):68–100. doi:10.1210/edrv.20.1.0357.PubMedGoogle Scholar
  73. Banks WA. The blood-brain barrier as a regulatory interface in the gut-brain axes. Physiol Behav. 2006;89(4):472–6. doi:10.1016/j.physbeh.2006.07.004.PubMedView ArticleGoogle Scholar
  74. Suzuki K, Simpson KA, Minnion JS, Shillito JC, Bloom SR. The role of gut hormones and the hypothalamus in appetite regulation. Endocr J. 2010;57(5):359–72.PubMedView ArticleGoogle Scholar
  75. Begg DP, Woods SC. The endocrinology of food intake. Nat Rev Endocrinol. 2013;9(10):584–97. doi:10.1038/nrendo.2013.136.PubMedView ArticleGoogle Scholar
  76. Simpson K, Parker J, Plumer J, Bloom S. CCK, PYY and PP: the control of energy balance. Handb Exp Pharmacol. 2012;209:209–30. doi:10.1007/978-3-642-24716-3_9.PubMedView ArticleGoogle Scholar
  77. Druce MR, Small CJ, Bloom SR. Minireview: gut peptides regulating satiety. Endocrinology. 2004;145(6):2660–5. doi:10.1210/en.2004-0089.PubMedView ArticleGoogle Scholar
  78. Konturek PC, Konturek JW, Czesnikiewicz-Guzik M, Brzozowski T, Sito E, Konturek SJ. Neuro-hormonal control of food intake: basic mechanisms and clinical implications. J Physiol Pharmacol. 2005;56 Suppl 6:5–25.Google Scholar
  79. Scott TR, Yaxley S, Sienkiewicz ZJ, Rolls ET. Gustatory responses in the frontal opercular cortex of the alert cynomolgus monkey. J Neurophysiol. 1986;56(3):876–90.PubMedGoogle Scholar
  80. Yaxley S, Rolls ET, Sienkiewicz ZJ. The responsiveness of neurons in the insular gustatory cortex of the macaque monkey is independent of hunger. Physiol Behav. 1988;42(3):223–9.PubMedView ArticleGoogle Scholar
  81. Scott TR, Plata-Salaman CR, Smith VL, Giza BK. Gustatory neural coding in the monkey cortex: stimulus intensity. J Neurophysiol. 1991;65(1):76–86.PubMedGoogle Scholar
  82. Ito S, Ogawa H. Neural activities in the fronto-opercular cortex of macaque monkeys during tasting and mastication. Jpn J Physiol. 1994;44(2):141–56.PubMedView ArticleGoogle Scholar
  83. Rolls ET, Scott TR, Sienkiewicz ZJ, Yaxley S. The responsiveness of neurones in the frontal opercular gustatory cortex of the macaque monkey is independent of hunger. J Physiol. 1988;397:1–12.PubMedPubMed CentralView ArticleGoogle Scholar
  84. Yaxley S, Rolls ET, Sienkiewicz ZJ, Scott TR. Satiety does not affect gustatory activity in the nucleus of the solitary tract of the alert monkey. Brain Res. 1985;347(1):85–93.PubMedView ArticleGoogle Scholar
  85. Giza BK, Scott TR, Vanderweele DA. Administration of satiety factors and gustatory responsiveness in the nucleus tractus solitarius of the rat. Brain Res Bull. 1992;28(4):637–9.PubMedView ArticleGoogle Scholar
  86. Scott TR, Small DM. The role of the parabrachial nucleus in taste processing and feeding. Ann N Y Acad Sci. 2009;1170:372–7. doi:10.1111/j.1749-6632.2009.03906.x.PubMedView ArticleGoogle Scholar
  87. Rolls ET. Emotion and decision-making explained. Oxford, UK: Oxford University Press; 2014.Google Scholar
  88. Rolls ET. Taste, olfactory, and food reward value processing in the brain. Progress in neurobiology. 2015;127-128C:64–90. doi:10.1016/j.pneurobio.2015.03.002.
  89. Rolls ET. Functions of the anterior insula in taste, autonomic, and related functions. Brain and cognition. 2015. doi:10.1016/j.bandc.2015.07.002.
  90. Yasoshima Y, Yamamoto T. Short-term and long-term excitability changes of the insular cortical neurons after the acquisition of taste aversion learning in behaving rats. Neuroscience. 1998;84(1):1–5.PubMedView ArticleGoogle Scholar
  91. Bermudez-Rattoni F. The forgotten insular cortex: its role on recognition memory formation. Neurobiol Learn Mem. 2014;109:207–16. doi:10.1016/j.nlm.2014.01.001.PubMedView ArticleGoogle Scholar
  92. Miranda MI, Ferreira G, Ramirez-Lugo L, Bermudez-Rattoni F. Role of cholinergic system on the construction of memories: taste memory encoding. Neurobiol Learn Mem. 2003;80(3):211–22.PubMedView ArticleGoogle Scholar
  93. Scott TR. Learning through the taste system. Front Syst Neurosci. 2011;5:87. doi:10.3389/fnsys.2011.00087.PubMedPubMed CentralView ArticleGoogle Scholar
  94. Bermudez-Rattoni F, McGaugh JL. Insular cortex and amygdala lesions differentially affect acquisition on inhibitory avoidance and conditioned taste aversion. Brain Res. 1991;549(1):165–70.PubMedView ArticleGoogle Scholar
  95. Kaada BR, Pribram KH, Epstein JA. Respiratory and vascular responses in monkeys from temporal pole, insula, orbital surface and cingulate gyrus; a preliminary report. J Neurophysiol. 1949;12(5):347–56.PubMedGoogle Scholar
  96. Thorpe SJ, Rolls ET, Maddison S. The orbitofrontal cortex: neuronal activity in the behaving monkey. Exp Brain Res. 1983;49(1):93–115.PubMedView ArticleGoogle Scholar
  97. Takagi SF. The olfactory nervous system of the old world monkey. Jpn J Physiol. 1984;34(4):561–73.PubMedView ArticleGoogle Scholar
  98. Neafsey EJ. Prefrontal cortical control of the autonomic nervous system: anatomical and physiological observations. Prog Brain Res. 1990;85:147–65. discussion 65–6.PubMedView ArticleGoogle Scholar
  99. Rolls ET, Yaxley S, Sienkiewicz ZJ. Gustatory responses of single neurons in the caudolateral orbitofrontal cortex of the macaque monkey. J Neurophysiol. 1990;64(4):1055–66.PubMedGoogle Scholar
  100. Rolls ET, Critchley HD, Mason R, Wakeman EA. Orbitofrontal cortex neurons: role in olfactory and visual association learning. J Neurophysiol. 1996;75(5):1970–81.PubMedGoogle Scholar
  101. Verhagen JV, Rolls ET, Kadohisa M. Neurons in the primate orbitofrontal cortex respond to fat texture independently of viscosity. J Neurophysiol. 2003;90(3):1514–25. doi:10.1152/jn.00320.2003.PubMedView ArticleGoogle Scholar
  102. Carmichael ST, Price JL. Architectonic subdivision of the orbital and medial prefrontal cortex in the macaque monkey. J Comp Neurol. 1994;346(3):366–402. doi:10.1002/cne.903460305.PubMedView ArticleGoogle Scholar
  103. Ongur D, An X, Price JL. Prefrontal cortical projections to the hypothalamus in macaque monkeys. J Comp Neurol. 1998;401(4):480–505.PubMedView ArticleGoogle Scholar
  104. Kadohisa M, Rolls ET, Verhagen JV. Neuronal representations of stimuli in the mouth: the primate insular taste cortex, orbitofrontal cortex and amygdala. Chem Senses. 2005;30(5):401–19. doi:10.1093/chemse/bji036.PubMedView ArticleGoogle Scholar
  105. Padoa-Schioppa C, Assad JA. Neurons in the orbitofrontal cortex encode economic value. Nature. 2006;441(7090):223–6. doi:10.1038/nature04676.PubMedPubMed CentralView ArticleGoogle Scholar
  106. Tremblay L, Schultz W. Relative reward preference in primate orbitofrontal cortex. Nature. 1999;398(6729):704–8. doi:10.1038/19525.PubMedView ArticleGoogle Scholar
  107. Morrison SE, Salzman CD. The convergence of information about rewarding and aversive stimuli in single neurons. J Neurosci. 2009;29(37):11471–83. doi:10.1523/JNEUROSCI.1815-09.2009.PubMedPubMed CentralView ArticleGoogle Scholar
  108. Critchley HD, Rolls ET. Olfactory neuronal responses in the primate orbitofrontal cortex: analysis in an olfactory discrimination task. J Neurophysiol. 1996;75(4):1659–72.PubMedGoogle Scholar
  109. Critchley HD, Rolls ET. Hunger and satiety modify the responses of olfactory and visual neurons in the primate orbitofrontal cortex. J Neurophysiol. 1996;75(4):1673–86.PubMedGoogle Scholar
  110. Rolls ET, Sienkiewicz ZJ, Yaxley S. Hunger modulates the responses to gustatory stimuli of single neurons in the caudolateral orbitofrontal cortex of the macaque monkey. Eur J Neurosci. 1989;1(1):53–60.PubMedView ArticleGoogle Scholar
  111. Morrison SE, Saez A, Lau B, Salzman CD. Different time courses for learning-related changes in amygdala and orbitofrontal cortex. Neuron. 2011;71(6):1127–40. doi:10.1016/j.neuron.2011.07.016.PubMedPubMed CentralView ArticleGoogle Scholar
  112. Delgado JM, Livingston RB. Some respiratory, vascular and thermal responses to stimulation of orbital surface of frontal lobe. J Neurophysiol. 1948;11(1):39–55.PubMedGoogle Scholar
  113. Bailey P, Sweet WH. Effects on respiration, blood pressure and gastric motility of stimulation of orbital surface of frontal lobe. Neurophysiology. 1940;3:276–81.Google Scholar
  114. Gabbott PL, Warner TA, Jays PR, Bacon SJ. Areal and synaptic interconnectivity of prelimbic (area 32), infralimbic (area 25) and insular cortices in the rat. Brain Res. 2003;993(1–2):59–71.PubMedView ArticleGoogle Scholar
  115. Price JL, Amaral DG. An autoradiographic study of the projections of the central nucleus of the monkey amygdala. J Neurosci. 1981;1(11):1242–59.PubMedGoogle Scholar
  116. Barbas H, Saha S, Rempel-Clower N, Ghashghaei T. Serial pathways from primate prefrontal cortex to autonomic areas may influence emotional expression. BMC Neurosci. 2003;4:25. doi:10.1186/1471-2202-4-25.PubMedPubMed CentralView ArticleGoogle Scholar
  117. Rolls ET. Functions of the orbitofrontal and pregenual cingulate cortex in taste, olfaction, appetite and emotion. Acta Physiol Hung. 2008;95(2):131–64. doi:10.1556/APhysiol.95.2008.2.1.PubMedView ArticleGoogle Scholar
  118. Jezzini A, Mazzucato L, La Camera G, Fontanini A. Processing of hedonic and chemosensory features of taste in medial prefrontal and insular networks. J Neurosci. 2013;33(48):18966–78. doi:10.1523/JNEUROSCI.2974-13.2013.PubMedPubMed CentralView ArticleGoogle Scholar
  119. Bouret S, Richmond BJ. Ventromedial and orbital prefrontal neurons differentially encode internally and externally driven motivational values in monkeys. J Neurosci. 2010;30(25):8591–601. doi:10.1523/JNEUROSCI.0049-10.2010.PubMedPubMed CentralView ArticleGoogle Scholar
  120. Niki H, Watanabe M. Prefrontal and cingulate unit activity during timing behavior in the monkey. Brain Res. 1979;171(2):213–24.PubMedView ArticleGoogle Scholar
  121. Matsumoto M, Matsumoto K, Abe H, Tanaka K. Medial prefrontal cell activity signaling prediction errors of action values. Nat Neurosci. 2007;10(5):647–56. doi:10.1038/nn1890.PubMedView ArticleGoogle Scholar
  122. Smith WK. The functional significance of the rostral cingular cortex as revealed by its responses to electrical excitation. Neurophysiology. 1945;8:241–55.Google Scholar
  123. Ward Jr AA. The cingular gyrus, area 24. J Neurophysiol. 1948;11(1):13–23.PubMedGoogle Scholar
  124. Kennerley SW, Walton ME, Behrens TE, Buckley MJ, Rushworth MF. Optimal decision making and the anterior cingulate cortex. Nat Neurosci. 2006;9(7):940–7. doi:10.1038/nn1724.PubMedView ArticleGoogle Scholar
  125. Bernard JF, Alden M, Besson JM. The organization of the efferent projections from the pontine parabrachial area to the amygdaloid complex: a Phaseolus vulgaris leucoagglutinin (PHA-L) study in the rat. J Comp Neurol. 1993;329(2):201–29. doi:10.1002/cne.903290205.PubMedView ArticleGoogle Scholar
  126. Saper CB. The central autonomic nervous system: conscious visceral perception and autonomic pattern generation. Annu Rev Neurosci. 2002;25:433–69. doi:10.1146/annurev.neuro.25.032502.111311.PubMedView ArticleGoogle Scholar
  127. Aggleton JP, Burton MJ, Passingham RE. Cortical and subcortical afferents to the amygdala of the rhesus monkey (Macaca mulatta). Brain Res. 1980;190(2):347–68.PubMedView ArticleGoogle Scholar
  128. Mufson EJ, Mesulam MM, Pandya DN. Insular interconnections with the amygdala in the rhesus monkey. Neuroscience. 1981;6(7):1231–48.PubMedView ArticleGoogle Scholar
  129. Amaral DG, Price JL. Amygdalo-cortical projections in the monkey (Macaca fascicularis). J Comp Neurol. 1984;230(4):465–96. doi:10.1002/cne.902300402.PubMedView ArticleGoogle Scholar
  130. Pitkanen A, Amaral DG. Organization of the intrinsic connections of the monkey amygdaloid complex: projections originating in the lateral nucleus. J Comp Neurol. 1998;398(3):431–58.PubMedView ArticleGoogle Scholar
  131. Fudge JL, Kunishio K, Walsh P, Richard C, Haber SN. Amygdaloid projections to ventromedial striatal subterritories in the primate. Neuroscience. 2002;110(2):257–75.PubMedView ArticleGoogle Scholar
  132. Scott TR, Karadi Z, Oomura Y, Nishino H, Plata-Salaman CR, Lenard L, et al. Gustatory neural coding in the amygdala of the alert macaque monkey. J Neurophysiol. 1993;69(6):1810–20.PubMedGoogle Scholar
  133. Kadohisa M, Verhagen JV, Rolls ET. The primate amygdala: neuronal representations of the viscosity, fat texture, temperature, grittiness and taste of foods. Neuroscience. 2005;132(1):33–48. doi:10.1016/j.neuroscience.2004.12.005.PubMedView ArticleGoogle Scholar
  134. Balleine BW, Killcross S. Parallel incentive processing: an integrated view of amygdala function. Trends Neurosci. 2006;29(5):272–9. doi:10.1016/j.tins.2006.03.002.PubMedView ArticleGoogle Scholar
  135. Corbit LH, Balleine BW. Double dissociation of basolateral and central amygdala lesions on the general and outcome-specific forms of pavlovian-instrumental transfer. J Neurosci. 2005;25(4):962–70. doi:10.1523/JNEUROSCI.4507-04.2005.PubMedView ArticleGoogle Scholar
  136. Yasoshima Y, Shimura T, Yamamoto T. Single unit responses of the amygdala after conditioned taste aversion in conscious rats. Neuroreport. 1995;6(17):2424–8.PubMedView ArticleGoogle Scholar
  137. Nishijo H, Ono T, Nishino H. Single neuron responses in amygdala of alert monkey during complex sensory stimulation with affective significance. J Neurosci. 1988;8(10):3570–83.PubMedGoogle Scholar
  138. Paton JJ, Belova MA, Morrison SE, Salzman CD. The primate amygdala represents the positive and negative value of visual stimuli during learning. Nature. 2006;439(7078):865–70. doi:10.1038/nature04490.PubMedPubMed CentralView ArticleGoogle Scholar
  139. Sanghera MK, Rolls ET, Roper-Hall A. Visual responses of neurons in the dorsolateral amygdala of the alert monkey. Exp Neurol. 1979;63(3):610–26.PubMedView ArticleGoogle Scholar
  140. Wellman LL, Gale K, Malkova L. GABAA-mediated inhibition of basolateral amygdala blocks reward devaluation in macaques. J Neurosci. 2005;25(18):4577–86. doi:10.1523/JNEUROSCI.2257-04.2005.PubMedView ArticleGoogle Scholar
  141. Yan J, Scott TR. The effect of satiety on responses of gustatory neurons in the amygdala of alert cynomolgus macaques. Brain Res. 1996;740(1–2):193–200.PubMedView ArticleGoogle Scholar
  142. Rempel-Clower NL, Barbas H. Topographic organization of connections between the hypothalamus and prefrontal cortex in the rhesus monkey. J Comp Neurol. 1998;398(3):393–419.PubMedView ArticleGoogle Scholar
  143. Morecraft RJ, Geula C, Mesulam MM. Cytoarchitecture and neural afferents of orbitofrontal cortex in the brain of the monkey. J Comp Neurol. 1992;323(3):341–58. doi:10.1002/cne.903230304.PubMedView ArticleGoogle Scholar
  144. Tanabe T, Yarita H, Iino M, Ooshima Y, Takagi SF. An olfactory projection area in orbitofrontal cortex of the monkey. J Neurophysiol. 1975;38(5):1269–83.PubMedGoogle Scholar
  145. Aponte Y, Atasoy D, Sternson SM. AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training. Nat Neurosci. 2011;14(3):351–5. doi:10.1038/nn.2739.PubMedPubMed CentralView ArticleGoogle Scholar
  146. Atasoy D, Betley JN, Su HH, Sternson SM. Deconstruction of a neural circuit for hunger. Nature. 2012;488(7410):172–7. doi:10.1038/nature11270.PubMedPubMed CentralView ArticleGoogle Scholar
  147. Krashes MJ, Shah BP, Madara JC, Olson DP, Strochlic DE, Garfield AS, et al. An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger. Nature. 2014;507(7491):238–42. doi:10.1038/nature12956.PubMedPubMed CentralView ArticleGoogle Scholar
  148. O'Malley D, Reimann F, Simpson AK, Gribble FM. Sodium-coupled glucose cotransporters contribute to hypothalamic glucose sensing. Diabetes. 2006;55(12):3381–6. doi:10.2337/db06-0531.PubMedPubMed CentralView ArticleGoogle Scholar
  149. Burton MJ, Rolls ET, Mora F. Effects of hunger on the responses of neurons in the lateral hypothalamus to the sight and taste of food. Exp Neurol. 1976;51(3):668–77.PubMedView ArticleGoogle Scholar
  150. Rolls ET, Murzi E, Yaxley S, Thorpe SJ, Simpson SJ. Sensory-specific satiety: food-specific reduction in responsiveness of ventral forebrain neurons after feeding in the monkey. Brain Res. 1986;368(1):79–86.PubMedView ArticleGoogle Scholar
  151. Baxter MG, Parker A, Lindner CC, Izquierdo AD, Murray EA. Control of response selection by reinforcer value requires interaction of amygdala and orbital prefrontal cortex. J Neurosci. 2000;20(11):4311–9.PubMedGoogle Scholar
  152. Pears A, Parkinson JA, Hopewell L, Everitt BJ, Roberts AC. Lesions of the orbitofrontal but not medial prefrontal cortex disrupt conditioned reinforcement in primates. J Neurosci. 2003;23(35):11189–201.PubMedGoogle Scholar
  153. Faurion A, Cerf B, Le Bihan D, Pillias AM. fMRI study of taste cortical areas in humans. Ann N Y Acad Sci. 1998;855:535–45.PubMedView ArticleGoogle Scholar
  154. de Araujo IE, Kringelbach ML, Rolls ET, Hobden P. Representation of umami taste in the human brain. J Neurophysiol. 2003;90(1):313–9. doi:10.1152/jn.00669.2002.PubMedView ArticleGoogle Scholar
  155. Critchley HD. Neural mechanisms of autonomic, affective, and cognitive integration. J Comp Neurol. 2005;493(1):154–66. doi:10.1002/cne.20749.PubMedView ArticleGoogle Scholar
  156. O'Doherty J, Rolls ET, Francis S, Bowtell R, McGlone F. Representation of pleasant and aversive taste in the human brain. J Neurophysiol. 2001;85(3):1315–21.PubMedGoogle Scholar
  157. Small DM, Gregory MD, Mak YE, Gitelman D, Mesulam MM, Parrish T. Dissociation of neural representation of intensity and affective valuation in human gustation. Neuron. 2003;39(4):701–11.PubMedView ArticleGoogle Scholar
  158. Small DM, Bender G, Veldhuizen MG, Rudenga K, Nachtigal D, Felsted J. The role of the human orbitofrontal cortex in taste and flavor processing. Ann N Y Acad Sci. 2007;1121:136–51. doi:10.1196/annals.1401.002.PubMedView ArticleGoogle Scholar
  159. Kringelbach ML, O'Doherty J, Rolls ET, Andrews C. Activation of the human orbitofrontal cortex to a liquid food stimulus is correlated with its subjective pleasantness. Cereb Cortex. 2003;13(10):1064–71.PubMedView ArticleGoogle Scholar
  160. Batterham RL, Ffytche DH, Rosenthal JM, Zelaya FO, Barker GJ, Withers DJ, et al. PYY modulation of cortical and hypothalamic brain areas predicts feeding behaviour in humans. Nature. 2007;450(7166):106–9. doi:10.1038/nature06212.PubMedView ArticleGoogle Scholar
  161. Malik S, McGlone F, Bedrossian D, Dagher A. Ghrelin modulates brain activity in areas that control appetitive behavior. Cell Metab. 2008;7(5):400–9. doi:10.1016/j.cmet.2008.03.007.PubMedView ArticleGoogle Scholar
  162. Grabenhorst F, Rolls ET, Bilderbeck A. How cognition modulates affective responses to taste and flavor: top-down influences on the orbitofrontal and pregenual cingulate cortices. Cereb Cortex. 2008;18(7):1549–59. doi:10.1093/cercor/bhm185.PubMedView ArticleGoogle Scholar
  163. Grabenhorst F, Rolls ET. Selective attention to affective value alters how the brain processes taste stimuli. Eur J Neurosci. 2008;27(3):723–9. doi:10.1111/j.1460-9568.2008.06033.x.PubMedView ArticleGoogle Scholar
  164. Allman JM, Hakeem A, Erwin JM, Nimchinsky E, Hof P. The anterior cingulate cortex. The evolution of an interface between emotion and cognition. Ann N Y Acad Sci. 2001;935:107–17.PubMedView ArticleGoogle Scholar
  165. Grabenhorst F, Rolls ET. Value, pleasure and choice in the ventral prefrontal cortex. Trends Cogn Sci. 2011;15(2):56–67. doi:10.1016/j.tics.2010.12.004.PubMedView ArticleGoogle Scholar
  166. Sheth SA, Mian MK, Patel SR, Asaad WF, Williams ZM, Dougherty DD, et al. Human dorsal anterior cingulate cortex neurons mediate ongoing behavioural adaptation. Nature. 2012;488(7410):218–21. doi:10.1038/nature11239.PubMedPubMed CentralView ArticleGoogle Scholar
  167. Walton ME, Devlin JT, Rushworth MF. Interactions between decision making and performance monitoring within prefrontal cortex. Nat Neurosci. 2004;7(11):1259–65. doi:10.1038/nn1339.PubMedView ArticleGoogle Scholar
  168. Cassady BA, Considine RV, Mattes RD. Beverage consumption, appetite, and energy intake: what did you expect? Am J Clin Nutr. 2012;95(3):587–93. doi:10.3945/ajcn.111.025437.PubMedPubMed CentralView ArticleGoogle Scholar
  169. Provencher V, Polivy J, Herman CP. Perceived healthiness of food. If it’s healthy, you can eat more! Appetite. 2009;52(2):340–4. doi:10.1016/j.appet.2008.11.005.PubMedView ArticleGoogle Scholar
  170. Schioth HB, Ferriday D, Davies SR, Benedict C, Elmstahl H, Brunstrom JM, et al. Are you sure? Confidence about the satiating capacity of a food affects subsequent food intake. Nutrients. 2015;7(7):5088–97. doi:10.3390/nu7075088.PubMedPubMed CentralView ArticleGoogle Scholar
  171. Nicolaidis S, Rowland N. Intravenous self-feeding: long-term regulation of energy balance in rats. Science. 1977;195(4278):589–91.PubMedView ArticleGoogle Scholar
  172. Sclafani A. Oral and postoral determinants of food reward. Physiol Behav. 2004;81(5):773–9. doi:10.1016/j.physbeh.2004.04.031.PubMedView ArticleGoogle Scholar
  173. Booth DA. Food-conditioned eating preferences and aversions with interoceptive elements: conditioned appetites and satieties. Ann N Y Acad Sci. 1985;443:22–41.PubMedView ArticleGoogle Scholar
  174. Sclafani A. Gut-brain nutrient signaling. Appetition vs satiation Appetite. 2013;71:454–8. doi:10.1016/j.appet.2012.05.024.PubMedView ArticleGoogle Scholar
  175. Gibbs J, Falasco JD. Sham feeding in the rhesus monkey. Physiol Behav. 1978;20(3):245–9.PubMedView ArticleGoogle Scholar
  176. Gibbs J, Maddison SP, Rolls ET. Satiety role of the small intestine examined in sham-feeding rhesus monkeys. J Comp Physiol Psychol. 1981;95(6):1003–15.PubMedView ArticleGoogle Scholar
  177. Rolls ET. Central nervous mechanisms related to feeding and appetite. Br Med Bull. 1981;37(2):131–4.PubMedGoogle Scholar
  178. Raynor HA, Epstein LH. Dietary variety, energy regulation, and obesity. Psychol Bull. 2001;127(3):325–41.PubMedView ArticleGoogle Scholar
  179. Yamamoto T. Taste responses of cortical neurons. Prog Neurobiol. 1984;23(4):273–315.PubMedView ArticleGoogle Scholar
  180. Davis CM, Riley AL. Conditioned taste aversion learning: implications for animal models of drug abuse. Ann N Y Acad Sci. 2010;1187:247–75. doi:10.1111/j.1749-6632.2009.05147.x.PubMedView ArticleGoogle Scholar
  181. Guzman-Ramos K, Bermudez-Rattoni F. Post-learning molecular reactivation underlies taste memory consolidation. Front Syst Neurosci. 2011;5:79. doi:10.3389/fnsys.2011.00079.PubMedPubMed CentralView ArticleGoogle Scholar
  182. Lin JY, Arthurs J, Reilly S. Conditioned taste aversion, drugs of abuse and palatability. Neurosci Biobehav Rev. 2014;45C:28–45. doi:10.1016/j.neubiorev.2014.05.001.View ArticleGoogle Scholar
  183. Logue AW, Ophir I, Strauss KE. The acquisition of taste aversions in humans. Behav Res Ther. 1981;19(4):319–33.PubMedView ArticleGoogle Scholar
  184. Ackroff K, Sclafani A. Energy density and macronutrient composition determine flavor preference conditioned by intragastric infusions of mixed diets. Physiol Behav. 2006;89(2):250–60. doi:10.1016/j.physbeh.2006.06.003.PubMedView ArticleGoogle Scholar
  185. Ackroff K, Sclafani A. Rapid post-oral stimulation of intake and flavor conditioning in rats by glucose but not a non-metabolizable glucose analog. Physiol Behav. 2014;133:92–8. doi:10.1016/j.physbeh.2014.04.042.PubMedPubMed CentralView ArticleGoogle Scholar
  186. de Araujo IE, Ferreira JG, Tellez LA, Ren X, Yeckel CW. The gut-brain dopamine axis: a regulatory system for caloric intake. Physiol Behav. 2012;106(3):394–9. doi:10.1016/j.physbeh.2012.02.026.PubMedPubMed CentralView ArticleGoogle Scholar
  187. Zukerman S, Ackroff K, Sclafani A. Rapid post-oral stimulation of intake and flavor conditioning by glucose and fat in the mouse. Am J Physiol Regul Integr Comp Physiol. 2011;301(6):R1635–47. doi:10.1152/ajpregu.00425.2011.PubMedPubMed CentralView ArticleGoogle Scholar
  188. Sclafani A, Glass DS, Margolskee RF, Glendinning JI. Gut T1R3 sweet taste receptors do not mediate sucrose-conditioned flavor preferences in mice. Am J Physiol Regul Integr Comp Physiol. 2010;299(6):R1643–50. doi:10.1152/ajpregu.00495.2010.PubMedPubMed CentralView ArticleGoogle Scholar
  189. Sclafani A, Ackroff K, Schwartz GJ. Selective effects of vagal deafferentation and celiac-superior mesenteric ganglionectomy on the reinforcing and satiating action of intestinal nutrients. Physiol Behav. 2003;78(2):285–94.PubMedView ArticleGoogle Scholar
  190. Zukerman S, Ackroff K, Sclafani A. Post-oral appetite stimulation by sugars and nonmetabolizable sugar analogs. Am J Physiol Regul Integr Comp Physiol. 2013;305(7):R840–53. doi:10.1152/ajpregu.00297.2013.PubMedPubMed CentralView ArticleGoogle Scholar
  191. Sclafani A, Fanizza LJ, Azzara AV. Conditioned flavor avoidance, preference, and indifference produced by intragastric infusions of galactose, glucose, and fructose in rats. Physiol Behav. 1999;67(2):227–34.PubMedView ArticleGoogle Scholar
  192. Ackroff K, Touzani K, Peets TK, Sclafani A. Flavor preferences conditioned by intragastric fructose and glucose: differences in reinforcement potency. Physiol Behav. 2001;72(5):691–703.PubMedView ArticleGoogle Scholar
  193. Sclafani A, Ackroff K. Flavor preferences conditioned by intragastric glucose but not fructose or galactose in C57BL/6 J mice. Physiol Behav. 2012;106(4):457–61. doi:10.1016/j.physbeh.2012.03.008.PubMedPubMed CentralView ArticleGoogle Scholar
  194. Yiin YM, Ackroff K, Sclafani A. Flavor preferences conditioned by intragastric nutrient infusions in food restricted and free-feeding rats. Physiol Behav. 2005;84(2):217–31. doi:10.1016/j.physbeh.2004.11.008.PubMedView ArticleGoogle Scholar
  195. Rolls BJ, Hetherington M, Laster LJ. Comparison of the effects of aspartame and sucrose on appetite and food intake. Appetite. 1988;11 Suppl 1:62–7.PubMedView ArticleGoogle Scholar
  196. O'Doherty J, Rolls ET, Francis S, Bowtell R, McGlone F, Kobal G, et al. Sensory-specific satiety-related olfactory activation of the human orbitofrontal cortex. Neuroreport. 2000;11(4):893–7.PubMedView ArticleGoogle Scholar
  197. Gottfried JA, O'Doherty J, Dolan RJ. Encoding predictive reward value in human amygdala and orbitofrontal cortex. Science. 2003;301(5636):1104–7. doi:10.1126/science.1087919.PubMedView ArticleGoogle Scholar
  198. Midkiff EE, Bernstein IL. Targets of learned food aversions in humans. Physiol Behav. 1985;34(5):839–41.PubMedView ArticleGoogle Scholar
  199. Arwas S, Rolnick A, Lubow RE. Conditioned taste aversion in humans using motion-induced sickness as the US. Behav Res Ther. 1989;27(3):295–301.PubMedView ArticleGoogle Scholar
  200. Okifuji A, Friedman AG. Experimentally induced taste aversions in humans: effects of overshadowing on acquisition. Behav Res Ther. 1992;30(1):23–32.PubMedView ArticleGoogle Scholar
  201. Gibson EL, Wainwright CJ, Booth DA. Disguised protein in lunch after low-protein breakfast conditions food-flavor preferences dependent on recent lack of protein intake. Physiol Behav. 1995;58(2):363–71.PubMedView ArticleGoogle Scholar
  202. Drewnowski A, Massien C, Louis-Sylvestre J, Fricker J, Chapelot D, Apfelbaum M. Comparing the effects of aspartame and sucrose on motivational ratings, taste preferences, and energy intakes in humans. Am J Clin Nutr. 1994;59(2):338–45.PubMedGoogle Scholar
  203. Birch LL, McPhee L, Steinberg L, Sullivan S. Conditioned flavor preferences in young children. Physiol Behav. 1990;47(3):501–5.PubMedView ArticleGoogle Scholar
  204. Kern DL, McPhee L, Fisher J, Johnson S, Birch LL. The postingestive consequences of fat condition preferences for flavors associated with high dietary fat. Physiol Behav. 1993;54(1):71–6.PubMedView ArticleGoogle Scholar
  205. Masic U, Yeomans MR. Umami flavor enhances appetite but also increases satiety. Am J Clin Nutr. 2014;100(2):532–8. doi:10.3945/ajcn.113.080929.PubMedView ArticleGoogle Scholar
  206. van Avesaat M, Troost FJ, Ripken D, Peters J, Hendriks HF, Masclee AA. Intraduodenal infusion of a combination of tastants decreases food intake in humans. Am J Clin Nutr. 2015;102(4):729–35. doi:10.3945/ajcn.115.113266.PubMedView ArticleGoogle Scholar
  207. Yeomans MR, Gould NJ, Mobini S, Prescott J. Acquired flavor acceptance and intake facilitated by monosodium glutamate in humans. Physiol Behav. 2008;93(4–5):958–66. doi:10.1016/j.physbeh.2007.12.009.PubMedView ArticleGoogle Scholar
  208. Brooks SJ, O'Daly O, Uher R, Friederich HC, Giampietro V, Brammer M, et al. Thinking about eating food activates visual cortex with reduced bilateral cerebellar activation in females with anorexia nervosa: an fMRI study. PLoS One. 2012;7(3):e34000. doi:10.1371/journal.pone.0034000.PubMedPubMed CentralView ArticleGoogle Scholar
  209. Kaye WH, Wierenga CE, Bailer UF, Simmons AN, Bischoff-Grethe A. Nothing tastes as good as skinny feels: the neurobiology of anorexia nervosa. Trends Neurosci. 2013;36(2):110–20. doi:10.1016/j.tins.2013.01.003.PubMedView ArticleGoogle Scholar
  210. Small DM, Scott TR. Symposium overview: what happens to the pontine processing? Repercussions of interspecies differences in pontine taste representation for tasting and feeding. Ann N Y Acad Sci. 2009;1170:343–6. doi:10.1111/j.1749-6632.2009.03918.x.PubMedPubMed CentralView ArticleGoogle Scholar
  211. Passingham RE, Wise SP. The neurobiology of prefrontal cortex. Anatomy, evolution, and the origin of insight. Oxford: Oxford University Press; 2012.View ArticleGoogle Scholar

Copyright

© Kadohisa. 2015

Advertisement

Flavour

ISSN: 2044-7248