Gustatory Cortex Research Articles

Recognizing Taste: Coding Patterns Along the Neural Axis in Mammals.

The gustatory system encodes information about chemical identity, nutritional value, and concentration of sensory stimuli before transmitting the signal from taste buds to central neurons that process and transform the signal. Deciphering the coding logic for taste quality requires examining responses at each level along the neural axis-from peripheral sensory organs to gustatory cortex. From the earliest single-fiber recordings, it was clear that some afferent neurons respond uniquely and others to stimuli of multiple qualities. There is frequently a "best stimulus" for a given neuron, leading to the suggestion that taste exhibits "labeled line coding." In the extreme, a strict "labeled line" requires neurons and pathways dedicated to single qualities (e.g., sweet, bitter, etc.). At the other end of the spectrum, "across-fiber," "combinatorial," or "ensemble" coding requires minimal specific information to be imparted by a single neuron. Instead, taste quality information is encoded by simultaneous activity in ensembles of afferent fibers. Further, "temporal coding" models have proposed that certain features of taste quality may be embedded in the cadence of impulse activity. Taste receptor proteins are often expressed in nonoverlapping sets of cells in taste buds apparently supporting "labeled lines." Yet, taste buds include both narrowly and broadly tuned cells. As gustatory signals proceed to the hindbrain and on to higher centers, coding becomes more distributed and temporal patterns of activity become important. Here, we present the conundrum of taste coding in the light of current electrophysiological and imaging techniques at several levels of the gustatory processing pathway.

Gustation and Olfaction: The Importance of Place and Time

Animals can smell odors from the external environment or from their mouth via two routes: orthonasal and retronasal, respectively. Little is known about how the brain processes orthonasal and retronasal odors associated with taste, but a new study has revealed an important role for the gustatory cortex in such odor processing.

Retronasal Odor Perception Requires Taste Cortex, but Orthonasal Does Not

Smells can arise from a source external to the body and stimulate the olfactory epithelium upon inhalation through the nares (orthonasal olfaction). Alternatively, smells may arise from inside the mouth during consumption, stimulating the epithelium upon exhalation (retronasal olfaction). Both ortho- and retronasal olfaction produce highly salient percepts, but the two percepts have very different behavioral implications. Here, we use optogenetic manipulation in the context of a flavor preference learning paradigm to investigate differences in the neural circuits that process information in these two submodalities of olfaction. Our findings support a view in which retronasal, but not orthonasal, odors share processing circuitry commonly associated with taste. First, our behavioral results reveal that retronasal odors induce rapid preference learning and have a potentiating effect on orthonasal preference learning. Second, we demonstrate that inactivation of the insular gustatory cortex selectively impairs expression of retronasal preferences. Thus, orally sourced (retronasal) olfactory input is processed by a brain region responsible for taste processing, whereas externally sourced (orthonasal) olfactory input is not.

Sucrose intensity coding and decision-making in rat gustatory cortices.

Sucrose's sweet intensity is one attribute contributing to the overconsumption of high-energy palatable foods. However, it is not known how sucrose intensity is encoded and used to make perceptual decisions by neurons in taste-sensitive cortices. We trained rats in a sucrose intensity discrimination task and found that sucrose evoked a widespread response in neurons recorded in posterior-Insula (pIC), anterior-Insula (aIC), and Orbitofrontal cortex (OFC). Remarkably, only a few Intensity-selective neurons conveyed the most information about sucrose's intensity, indicating that for sweetness the gustatory system uses a compact and distributed code. Sucrose intensity was encoded in both firing-rates and spike-timing. The pIC, aIC, and OFC neurons tracked movement direction, with OFC neurons yielding the most robust response. aIC and OFC neurons encoded the subject's choices, whereas all three regions tracked reward omission. Overall, these multimodal areas provide a neural representation of perceived sucrose intensity, and of task-related information underlying perceptual decision-making.

Experience-Dependent c-Fos Expression in the Mediodorsal Thalamus Varies With Chemosensory Modality.

The mediodorsal thalamus is a higher order thalamic nucleus critical for many cognitive behaviors. Defined by its reciprocal connections with the prefrontal cortex, the mediodorsal thalamus receives strong projections from chemosensory cortical areas for taste and smell, gustatory cortex and piriform cortex. Recent studies indicate the mediodorsal thalamus is involved in experience-dependent chemosensory processes, including olfactory attention and discrimination and the hedonic perception of odor-taste mixtures. How novel and familiar chemosensory stimuli are represented within this structure remains unclear. Here, we compared the expression of c-Fos in the mediodorsal thalami of rats familiar with an odor, a taste, or an odor-taste mixture with those that sampled the stimuli for the first time. We found that familiar tastes or odor-taste mixtures induced significantly greater c-Fos expression in the mediodorsal thalamus than novel tastes or odor-taste mixtures, whereas novel odors induced greater c-Fos expression than familiar odors. These experience-dependent and modality-specific differences in c-Fos expression may relate to the behavioral relevance of the chemosensory stimulus, including odor neophobia. In a two-bottle brief-access preference task, rats preferred water to isoamyl acetate-odorized water over multiple days. However, after experience with isoamyl acetate mixed with sucrose (odor-taste mixture), the preference for water was eliminated. These findings demonstrate that experience with chemosensory stimuli modulates responses in the mediodorsal thalamus, suggesting this structure plays an integral role in communicating behaviorally relevant chemosensory information to higher order areas to guide food-related behaviors.

The role of the gustatory cortex in incidental experience-evoked enhancement of later taste learning.

The strength of learned associations between pairs of stimuli is affected by multiple factors, the most extensively studied of which is prior experience with the stimuli themselves. In contrast, little data is available regarding how experience with “incidental” stimuli (independent of any conditioning situation) impacts later learning. This lack of research is striking given the importance of incidental experience to survival. We have recently begun to fill this void using conditioned taste aversion (CTA), wherein an animal learns to avoid a taste that has been associated with malaise. We previously demonstrated that incidental exposure to salty and sour tastes (taste preexposure—TPE) enhances aversions learned later to sucrose. Here, we investigate the neurobiology underlying this phenomenon. First, we use immediate early gene (c-Fos) expression to identify gustatory cortex (GC) as a site at which TPE specifically increases the neural activation caused by taste-malaise pairing (i.e., TPE did not change c-Fos induced by either stimulus in isolation). Next, we use site-specific infection with the optical silencer Archaerhodopsin-T to show that GC inactivation during TPE inhibits the expected enhancements of both learning and CTA-related c-Fos expression, a full day later. Thus, we conclude that GC is almost certainly a vital part of the circuit that integrates incidental experience into later associative learning.

Gustatory responses in macaque monkeys revealed with fMRI: Comments on taste, taste preference, and internal state

Studies of the neural mechanisms underlying value-based decision making typically employ food or fluid rewards to motivate subjects to perform cognitive tasks. Rewards are often treated as interchangeable, but it is well known that the specific tastes of foods and fluids and the values associated with their taste sensations influence choices and contribute to overall levels of food consumption. Accordingly, we characterized the gustatory system in three macaque monkeys (Macaca mulatta) and examined whether gustatory responses were modulated by preferences and hydration status. To identify taste-responsive cortex, we delivered small quantities (0.1 ml) of sucrose (sweet), citric acid (sour), or distilled water in random order without any predictive cues while scanning monkeys using event-related fMRI. Neural effects were evaluated by using each session in each monkey as a data point in a second-level analysis. By contrasting BOLD responses to sweet and sour tastes with those from distilled water in a group level analysis, we identified taste responses in primary gustatory cortex area G, an adjacent portion of the anterior insular cortex, and prefrontal cortex area 12o. Choice tests administered outside the scanner revealed that all three monkeys strongly preferred sucrose to citric acid or water. BOLD responses in the ventral striatum, ventral pallidum, and amygdala reflected monkeys’ preferences, with greater BOLD responses to sucrose than citric acid. Finally, we examined the influence of hydration level by contrasting BOLD responses to receipt of fluids when monkeys were thirsty and after ad libitum water consumption. BOLD responses in area G and area 12o in the left hemisphere were greater following full hydration. By contrast, BOLD responses in portions of medial frontal cortex were reduced after ad libitum water consumption. These findings highlight brain regions involved in representing taste, taste preference and internal state.

A2011 Increased salt intake is associated with enhancement of neural salty preference in obesity

Objectives: Obesity and high intake of salt are major risk factors for hypertension and cardiometabolic diseases. Obese individuals often consume more dietary salt. We examined the neural effects underlying obesity-related high salt intake. Methods: A multi-center, random-order, double-blind taste study was conducted in the communities of four cities in China (n = 537). In addition,an interventional study was done in a local community in Chongqing, China, using positron emission tomography/computed tomography of the brain (n = 32). Results: Overweight/obese individuals tended to have a higher daily salt intake (2.0 g/day higher compared with normal-weight individuals after multivariable adjustment, 95% CI, 1.2–2.8 g/day, P < 0.001)and they exhibited reduced salt sensitivity and higher salt preference. Overweight/obese individuals had a higher prevalence of hypertension (33.3% vs. 12.9%, P < 0.001) and increased systolic blood pressure (132 ± 18 vs. 120 ± 16 mmHg, P < 0.001) and diastolic blood pressure (81 ± 12 vs. 74 ± 10 mmHg, P < 0.001) compared with normal-weight individuals. No sex-based differences were found for the body mass index, salt intake, or salt sensitivity. The altered salty taste and salty preference in overweight/obese individuals was related to increased activity in the orbitofrontal cortex (r = 0.44, P = 0.01), insula (0.38,0.03), and parahippocampus (0.37,0.04). Conclusion: Increased salt intake among overweight/obese individuals is associated with altered salt sensitivity and preferences related to abnormal activity of the gustatory cortex. It could be associated with the increased blood pressure observed in obesity.

Experience-dependent c-Fos expression in the primary chemosensory cortices of the rat

Eating a new food is a unique event that guides future food choices. A key element for these choices is the perception of flavor (odor-taste associations), a multisensory process dependent upon taste and smell. The two primary cortical areas for taste and smell, gustatory cortex and piriform cortex, are thought to be crucial regions for processing and responding to odor-taste mixtures. To determine how previous experience impacts the primary chemosensory cortices, we compared the expression of the immediate early gene, c-Fos, between rats presented with a taste, an odor, or an odor-taste mixture for the first-time with rats that had many days of prior experience. Compared to rats with prior experience, we found that first-time sampling of all three chemosensory stimuli led to significantly greater c-Fos expression in gustatory cortex. In piriform cortex, only the novel chemosensory stimuli containing odors showed greater c-Fos expression. These results indicate that prior experience with taste, odor, or odor-taste stimuli habituates responses in the primary chemosensory cortices and adds further evidence supporting gustatory cortex as a fundamental node for the integration of gustatory and olfactory signals.

Multisensory and Motor Representations in Rat Oral Somatosensory Cortex

In mammals, a complex array of oral sensors assess the taste, temperature and haptic properties of food. Although the representation of taste has been extensively studied in the gustatory cortex, it is unclear how the somatosensory cortex encodes information about the properties of oral stimuli. Moreover, it is poorly understood how different oral sensory modalities are integrated and how sensory responses are translated into oral motor actions. To investigate whether oral somatosensory cortex processes food-related sensations and movements, we performed in vivo whole-cell recordings and motor mapping experiments in rats. Neurons in oral somatosensory cortex showed robust post-synaptic and sparse action potential responses to air puffs. Membrane potential showed that cold water evoked larger responses than room temperature or hot water. Most neurons showed no clear tuning of responses to bitter, sweet and neutral gustatory stimuli. Finally, motor mapping experiments with histological verification revealed an initiation of movements related to food consumption behavior, such as jaw opening and tongue protrusions. We conclude that somatosensory cortex: (i) provides a representation of the temperature of oral stimuli, (ii) does not systematically encode taste information and (iii) influences orofacial movements related to food consummatory behavior.

Gustatory pathway in humans: A review of models of taste perception and their potential lateralization.

The focus of this review is to interpret recent advances in human gustatory pathways with respect to the laterality of gustatory responses. Psychophysical, neuroimaging, and clinical anatomical studies published in peer reviewed scientific journals were examined. From the anatomical and neuroimaging studies a total of six models are outlined and discussed in the light of some recent psychophysical and clinical results. In the specific of the salt condition and right preferred hand the outcomes have revealed a predominant left ipsilateral pathway with evidences of ipsilateral projection from the left primary gustatory cortex (PGC) to the orbitofrontal cortex, while a bilateral projection from the right oral cavity to the left and right insula seems to be more consistent. Also, the right side predominance of the chemosensory perception is objected. Additionally, the gustatory response appears to be dependent on the taste quality, supporting the idea of a chemotopical organization of the PGC as well as the Labelled-Line Model theory of peripheral taste quality encoding. However, where the fibers branch along the ascending pathway is not unequivocally established. Interestingly, factors like handedness appear to be remarkable when studying the lateralization of brain functions. Finally we suggest that further studies must include handedness and taste quality as distinctive factors that can help to interpret the results in a unique way.

The effects of amygdala and cortical inactivation on taste neophobia.

The current study examined the effects of transient inactivation of the basolateral amygdala (BLA; Experiment 1) and gustatory cortex (GC; Experiment 2) on the expression of taste neophobia and its recovery. We found that inactivation (induced by infusions of baclofen/muscimol) of each structure before exposure to a novel saccharin (0.5%) solution elevated intake on Trial 1 (i.e., taste neophobia was attenuated) and, surprisingly, decreased intake on Trial 2. It seems unlikely that this intake reduction on Trial 2 can be attributed to taste aversion learning caused by drug infusions because in the subsequent experiments with the same set of the implanted animals, the rats did not decrease intake when baclofen/muscimol was infused after taste presentation on Trial 1. The latter result suggests that BLA or GC inactivation that attenuates taste neophobia may also impair memory consolidation of a safe taste experience.

FMRI-Based Brain Responses to Quinine and Sucrose Gustatory Stimulation for Nutrition Research in the Minipig Model: A Proof-of-Concept Study.

The minipig model is of high interest for brain research in nutrition and associated pathologies considering the similarities to human nutritional physiology, brain structures, and functions. In the context of a gustatory stimulation paradigm, fMRI can provide crucial information about the sensory, cognitive, and hedonic integration of exteroceptive stimuli in healthy and pathological nutritional conditions. Our aims were (i) to validate the experimental setup, i.e., fMRI acquisition and SPM-based statistical analysis, with a visual stimulation; (ii) to implement the fMRI procedure in order to map the brain responses to different gustatory stimulations, i.e., sucrose (5%) and quinine (10 mM), and (ii) to investigate the differential effects of potentially aversive (quinine) and appetitive/pleasant (sucrose) oral stimulation on brain responses, especially in the limbic and reward circuits. Six Yucatan minipigs were imaged on an Avanto 1.5-T MRI under isoflurane anesthesia and mechanical ventilation. BOLD signal was recorded during visual or gustatory (artificial saliva, sucrose, or quinine) stimulation with a block paradigm. With the visual stimulation, brain responses were detected in the visual cortex, thus validating our experimental and statistical setup. Quinine and sucrose stimulation promoted different cerebral activation patterns that were concordant, to some extent, to results from human studies. The insular cortex (i.e., gustatory cortex) was activated with both sucrose and quinine, but other regions were specifically activated by one or the other stimulation. Gustatory stimulation combined with fMRI analysis in large animals such as minipigs is a promising approach to investigate the integration of gustatory stimulation in healthy or pathological conditions such as obesity, eating disorders, or dysgeusia. To date, this is the first intent to describe gustatory stimulation in minipigs using fMRI.

Encoding of Conditioned Taste Aversion in Cortico-Amygdala Circuits

Avoidance of potentially toxic food by means of conditioned taste aversion is critical for survival of many animals. However, the underlying neuronal mechanisms are poorly understood. Here, using two-photon calcium imaging of defined gustatory cortex neurons invivo, we show that conditioned taste aversion dynamically shifts neuronal population coding by stimulus-specific recruitment of neurons that project to the basolateral amygdala.

Adolescents at high risk of obesity show greater striatal response to increased sugar content in milkshakes

Children of overweight or obese parents are at a high risk of developing obesity. This study sought to examine the underlying neural factors related to parental obesity risk and the relative impact of sugar and fat when consuming a palatable food, as well as the impact of obesity risk status on brain response to appetizing food images. With the use of functional MRI, the responses of 108 healthy-weight adolescents [mean ± SD body mass index (kg/m2): 20.9±1.9; n=53 who were at high risk by virtue of parental obesity status, n=55 who were low risk] to food stimuli were examined. Stimuli included 4 milkshakes, which systematically varied in sugar and fat content, a calorie-free tasteless solution, and images of appetizing foods and glasses of water. High-risk compared with low-risk adolescents showed greater blood oxygen-dependent response to milkshakes (all variants collapsed) compared with the tasteless solution in the primary gustatory and oral somatosensory cortices (P-family-wise error rate <0.05), replicating a previous report. Notably, high-risk adolescents showed greater caudate, gustatory, and oral somatosensory responses to the high-sugar milkshake than to the tasteless solution; however, no effect of risk status was observed in the high-fat milkshake condition. Responses to food images were not related to obesity risk status. Collectively, the data presented here suggest that parental weight status is associated with greater striatal, gustatory, and somatosensory responses to palatable foods-in particular, high-sugar foods-in their adolescent offspring, which theoretically contributes to an increased risk of future overeating. This trial was registered at www.clinicaltrials.gov as NCT01949636.

Different Neural Processing of Umami and Salty Taste Determined by Umami Identification Ability Independent of Repeated Umami Exposure

There is a large inter-individual variation for umami taste perception. However the neural mechanism for this variability is not well understood. This study investigated brain responses to umami and salty taste among individuals with different umami identification abilities and the effect of repeated oral umami exposure on umami identification and neural processing of taste perceptions. Fifteen participants with high umami identification ability (“High Tasters, HT) and fifteen with low umami identification ability (“Low Tasters”, LT) underwent three weeks of controlled exposure to umami taste (umami training). Prior to and after the training, participants underwent fMRI scans during which the umami taste solution and a control taste (salty) solution were delivered to their mouth using a gustometer. Taste intensity and pleasantness were rated after each scan. Umami taste identification was assessed before and after the umami training using “Taste Strips” test. Neuroimaging results showed different central processing of umami and salty taste based on umami identification ability, in which the umami LT had stronger activation in the thalamus and hippocampus while the umami HT showed stronger activation in the primary gustatory cortex. In addition, umami identification was significantly improved after umami training for LT. However, it was not reflected in changes in neural activation. The current study shows that attention and association/memory related brain structures play a significant role in the perception of umami taste; and with reference to the results of repeated umami exposure, the presence of very subtle changes regarding the neural processing.

Anatomical Inputs From the Sensory and Value Structures to the Tail of the Rat Striatum.

The caudal region of the rodent striatum, called the tail of the striatum (TS), is a relatively small area but might have a distinct function from other striatal subregions. Recent primate studies showed that this part of the striatum has a unique function in encoding long-term value memory of visual objects for habitual behavior. This function might be due to its specific connectivity. We identified inputs to the rat TS and compared those with inputs to the dorsomedial striatum (DMS) in the same animals. The TS directly received anatomical inputs from both sensory structures and value-coding regions, but the DMS did not. First, inputs from the sensory cortex and sensory thalamus to the TS were found; visual, auditory, somatosensory and gustatory cortex and thalamus projected to the TS but not to the DMS. Second, two value systems innervated the TS; dopamine and serotonin neurons in the lateral part of the substantia nigra pars compacta (SNc) and dorsal raphe nucleus projected to the TS, respectively. The DMS received inputs from the separate group of dopamine neurons in the medial part of the SNc. In addition, learning-related regions of the limbic system innervated the TS; the temporal areas and the basolateral amygdala selectively innervated the TS, but not the DMS. Our data showed that both sensory and value-processing structures innervated the TS, suggesting its plausible role in value-guided sensory-motor association for habitual behavior.

Distribution of Fos-immunoreactive neurons in the gustatory cortex elicited by intra-oral infusion of taste solutions in conscious rats

The location of neurons in the gustatory cortex (GC) activated by intra-oral infusion of solutions in conscious rats was mapped using Fos immunohistochemistry. Groups of adult male Wistar rats (N's = 5) received an infusion of one of the following: dH2O, 0.1 or 1.0 M NaCl, 0.1 or 1.0 M sucrose, 0.32 M MSG (with 100 µM amiloride and 2.5 M inosine 5′-monophosphate), 0.03 M HCl, or 0.003 M QHCl delivered via an intra-oral cannula (0.233 ml/min for 5 min). Unstimulated control rats received no infusion. Taste reactivity (TR) behaviors were videotaped and scored. The number of Fos-immunoreactive (Fos-IR) neurons was counted in eight sections throughout the anterior-posterior extent of the GC in the medial and lateral halves of the granular (GI), dysgranular (DI), and dorsal (AID) and ventral (AIV) agranular insular cortices. Intra-oral infusion of dH2O, NaCl, or sucrose altered the number of Fos-IR neurons in only specific subareas of the GC and the effects of these tastants were concentration-dependent. For example, 1.0 M NaCl increased Fos-IR neurons in the posterior lateral AID and DI and elicited more aversive TR responses than 0.1 M NaCl. Compared to dH2O, infusions of HCl or QHCl increased the total number of Fos-IR neurons in many subareas of the GC throughout its anterior-posterior extent and increased aversive TR behaviors. Linear regression analyses suggested that neurons in the medial AID of the posterior GC may influence aversive behavioral responses to HCl and QHCl while neurons in the posterior lateral AID and DI may play a role in aversive TR responses to 1.0 M NaCl.

Neural correlates of taste reactivity in autism spectrum disorder

Selective or ‘picky’ eating habits are common among those with autism spectrum disorder (ASD). These behaviors are often related to aberrant sensory experience in individuals with ASD, including heightened reactivity to food taste and texture. However, very little is known about the neural mechanisms that underlie taste reactivity in ASD. In the present study, food-related neural responses were evaluated in 21 young adult and adolescent males diagnosed with ASD without intellectual disability, and 21 typically-developing (TD) controls. Taste reactivity was assessed using the Adolescent/Adult Sensory Profile, a clinical self-report measure. Functional magnetic resonance imaging was used to evaluate hemodynamic responses to sweet (vs. neutral) tastants and food pictures. Subjects also underwent resting-state functional connectivity scans.The ASD and TD individuals did not differ in their hemodynamic response to gustatory stimuli. However, the ASD subjects, but not the controls, exhibited a positive association between self-reported taste reactivity and the response to sweet tastants within the insular cortex and multiple brain regions associated with gustatory perception and reward. There was a strong interaction between diagnostic group and taste reactivity on tastant response in brain regions associated with ASD pathophysiology, including the bilateral anterior superior temporal sulcus (STS). This interaction of diagnosis and taste reactivity was also observed in the resting state functional connectivity between the anterior STS and dorsal mid-insula (i.e., gustatory cortex).These results suggest that self-reported heightened taste reactivity in ASD is associated with heightened brain responses to food-related stimuli and atypical functional connectivity of primary gustatory cortex, which may predispose these individuals to maladaptive and unhealthy patterns of selective eating behavior.Trial registration(clinicaltrials.gov identifier) NCT01031407. Registered: December 14, 2009.

Salt Appetite, and the Influence of Opioids.

Due to the biological importance of sodium and its relative scarcity within many natural environments, 'salt appetite' has evolved whereby dietary salt is highly sought after and palatable when tasted. In addition to peripheral responses, salt depletion is detected within the brain via circumventricular organs and 11β-hydroxysteroid dehydrogenase type 2 (HSD2) neurons to increase salt appetite. Salt appetite is comprised of two main components. One component is the incentive salience or motivation for salt (i.e. how much salt is 'wanted'). Incentive salience is dynamic and largely depends on internal homeostatic conditions in combination with the detection of relevant cues. It involves the mesolimbic system and structures such as the central amygdala, and opioid signalling within these regions can increase salt intake in rodents. A second key feature is the hedonic palatability of salt (i.e. how much it is 'liked') when it is tasted. After detection on the tongue, gustatory information passes through the brainstem nucleus of the solitary tract and thalamus, before being consciously detected within the gustatory cerebral cortex. The positive or negative hedonic value of this stimulus is also dynamic, and is encoded by a network including the nucleus accumbens, ventral pallidum, and lateral parabrachial nucleus. Opioid signalling within these areas can alter salt intake, and 'liking'. The overconsumption of dietary salt likely contributes to hypertension and associated diseases, and hence further characterising the role played by opioid signalling has important implications for human health.