Gustatory Cortex Neurons Research Articles

Cortical Coding of Gustatory and Thermal Signals in Active Licking Mice.

Eating behaviors are influenced by the integration of gustatory, olfactory, and somatosensory signals, which all contribute to the perception of flavor. Although extensive research has explored the neural correlates of taste in the gustatory cortex (GC), less is known about its role in encoding thermal information. This study investigates the encoding of oral thermal and chemosensory signals by GC neurons compared to the oral somatosensory cortex. In this study, we recorded the spiking activity of more than 900 GC neurons and 500 neurons from the oral somatosensory cortex in mice allowed to freely lick small drops of gustatory stimuli or deionized water at varying non-nociceptive temperatures. We then developed and used a Bayesian-based analysis technique to assess neural classification scores based on spike rate and phase timing within the lick cycle. Our results indicate that GC neurons rely predominantly on rate information, although phase information is needed to achieve maximum accuracy, to effectively encode both chemosensory and thermosensory signals. GC neurons can effectively differentiate between thermal stimuli, excelling in distinguishing both large contrasts (14°C vs. 36°C) and, although less effectively, more subtle temperature differences. Finally, a direct comparison of the decoding accuracy of thermosensory signals between the two cortices reveals that while the somatosensory cortex showed higher overall accuracy, the GC still encodes significant thermosensory information. These findings highlight the GC's dual role in processing taste and temperature, emphasizing the importance of considering temperature in future studies of taste processing.

Neuronal Activity in the Gustatory Cortex during Economic Choice.

An economic choice entails computing and comparing the values of individual offers. Offer values are represented in the orbitofrontal cortex (OFC)-an area that participates in value comparison-but it is unknown where offer values are computed in the first place. One possibility is that this computation takes place in OFC. Alternatively, offer values might be computed upstream of OFC. For choices between edible goods, a primary candidate is the gustatory region of the anterior insula (gustatory cortex, GC). Here we recorded from the GC of male rhesus monkeys choosing between different juice types. As a population, neurons in GC represented the flavor, the quantity, and the subjective value of the juice chosen by the animal. These variables were represented by distinct groups of cells and with different time courses. Specifically, chosen value signals emerged shortly after offer presentation, while neurons encoding the chosen juice and the chosen quantity peaked after juice delivery. Surprisingly, neurons in GC did not represent individual offer values in a systematic way. In a computational sense, the variables encoded in GC follow the process of value comparison. Thus our results argue against the hypothesis that offer values are computed in GC. At the same time, signals representing the subjective value of the expected reward indicate that responses in GC are not purely sensory. Thus neuronal responses in GC appear consummatory in nature.

Oral thermal processing in the gustatory cortex of awake mice.

Oral temperature is a sensory cue relevant to food preference and nutrition. To understand how orally sourced thermal inputs are represented in the gustatory cortex (GC), we recorded neural responses from the GC of male and female mice presented with deionized water at different innocuous temperatures (14 °C, 25 °C, and 36 °C) and taste stimuli (room temperature). Our results demonstrate that GC neurons encode orally sourced thermal information in the absence of classical taste qualities at the single neuron and population levels, as confirmed through additional experiments comparing GC neuron responses to water and artificial saliva. Analysis of thermal-evoked responses showed broadly tuned neurons that responded to temperature in a mostly monotonic manner. Spatial location may play a minor role regarding thermosensory activity; aside from the most ventral GC, neurons reliably responded to and encoded thermal information across the dorso-ventral and antero-postero cortical axes. Additional analysis revealed that more than half of the GC neurons that encoded chemosensory taste stimuli also accurately discriminated thermal information, providing additional evidence of the GC's involvement in processing thermosensory information important for ingestive behaviors. In terms of convergence, we found that GC neurons encoding information about both taste and temperature were broadly tuned and carried more information than taste-selective-only neurons; both groups encoded similar information about the palatability of stimuli. Altogether, our data reveal new details of the cortical code for the mammalian oral thermosensory system in behaving mice and pave the way for future investigations on GC functions and operational principles with respect to thermogustation.

Active Licking Shapes Cortical Taste Coding.

Neurons in the gustatory cortex (GC) represent taste through time-varying changes in their spiking activity. The predominant view is that the neural firing rate represents the sole unit of taste information. It is currently not known whether the phase of spikes relative to lick timing is used by GC neurons for taste encoding. To address this question, we recorded spiking activity from >500 single GC neurons in male and female mice permitted to freely lick to receive four liquid gustatory stimuli and water. We developed a set of data analysis tools to determine the ability of GC neurons to discriminate gustatory information and then to quantify the degree to which this information exists in the spike rate versus the spike timing or phase relative to licks. These tools include machine learning algorithms for classification of spike trains and methods from geometric shape and functional data analysis. Our results show that while GC neurons primarily encode taste information using a rate code, the timing of spikes is also an important factor in taste discrimination. A further finding is that taste discrimination using spike timing is improved when the timing of licks is considered in the analysis. That is, the interlick phase of spiking provides more information than the absolute spike timing itself. Overall, our analysis demonstrates that the ability of GC neurons to distinguish among tastes is best when spike rate and timing is interpreted relative to the timing of licks.SIGNIFICANCE STATEMENT Neurons represent information from the outside world via changes in their number of action potentials (spikes) over time. This study examines how neurons in the mouse gustatory cortex (GC) encode taste information when gustatory stimuli are experienced through the active process of licking. We use electrophysiological recordings and data analysis tools to evaluate the ability of GC neurons to distinguish tastants and then to quantify the degree to which this information exists in the spike rate versus the spike timing relative to licks. We show that the neuron's ability to distinguish between tastes is higher when spike rate and timing are interpreted relative to the timing of licks, indicating that the lick cycle is a key factor for taste processing.

LiCl-induced sickness modulates rat gustatory cortical responses.

Gustatory cortex (GC), a structure deeply involved in the making of consumption decisions, presumably performs this function by integrating information about taste, experiences, and internal states related to the animal's health, such as illness. Here, we investigated this assertion, examining whether illness is represented in GC activity, and how this representation impacts taste responses and behavior. We recorded GC single-neuron activity and local field potentials (LFPs) from healthy rats and rats made ill (via LiCl injection). We show (consistent with the extant literature) that the onset of illness-related behaviors arises contemporaneously with alterations in 7 to 12 Hz LFP power at approximately 12 min following injection. This process was accompanied by reductions in single-neuron taste response magnitudes and discriminability, and with enhancements in palatability-relatedness-a result reflecting the collapse of responses toward a simple "good-bad" code visible in the entire sample, but focused on a specific subset of GC neurons. Overall, our data show that a state (illness) that profoundly reduces consumption changes basic properties of the sensory cortical response to tastes, in a manner that can easily explain illness' impact on consumption.

ApoE4 attenuates cortical neuronal activity in young behaving apoE4 rats

The E4 allele of apolipoprotein E (apoE4) is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). However, apoE4 may cause innate brain abnormalities before the appearance of AD-related neuropathology. Understanding these primary dysfunctions is vital for the early detection of AD and the development of therapeutic strategies. Recently we reported impaired extra-hippocampal memory in young apoE4 mice, a deficit that was correlated with attenuated structural pre-synaptic plasticity in cortical and subcortical regions. Here we tested the hypothesis that these early structural deficits impact learning via changes in basal and stimuli evoked neuronal activity. We recorded extracellular neuronal activity from the gustatory cortex (GC) of three-month-old humanized apoE4 (hApoE4) and wildtype rats expressing rat apoE (rAE), before and after conditioned taste aversion (CTA) training. Despite normal sucrose drinking behavior before CTA, young hApoE4 rats showed impaired CTA learning, consistent with our previous results in target-replacement apoE4 mice. This behavioral deficit was correlated with decreased basal and taste-evoked firing rates in both putative excitatory and inhibitory GC neurons. Further taste coding analyses at the single neuron and ensemble levels revealed that GC neurons of the hApoE4 group correctly classified tastes, but were unable to undergo plasticity to support learning. These results suggest that apoE4 impacts brain excitability and plasticity early in life that may act as an initiator for later AD pathologies.

Layer- and Cell Type-Specific Response Properties of Gustatory Cortex Neurons in Awake Mice.

Studies in visual, auditory, and somatosensory cortices have revealed that different cell types as well as neurons located in different laminae display distinct stimulus response profiles. The extent to which these layer and cell type-specific distinctions generalize to gustatory cortex (GC) remains unknown. In this study, we performed extracellular recordings in adult female mice to monitor the activity of putative pyramidal and inhibitory neurons located in deep and superficial layers of GC. Awake, head-restrained mice were trained to lick different tastants (sucrose, salt, citric acid, quinine, and water) from a lick spout. We found that deep layer neurons show higher baseline firing rates (FRs) in GC with deep-layer inhibitory neurons displaying highest FRs at baseline and following the stimulus. GC's activity shows robust modulations before animals' contact with tastants, and this phenomenon is most prevalent in deep-layer inhibitory neurons. Furthermore, we show that licking activity strongly shapes the spiking pattern of GC pyramidal neurons, eliciting phase-locked spiking across trials and tastants. We demonstrate that there is a greater percentage of taste-coding neurons in deep versus superficial layers with chemosensitive neurons across all categories showing similar breadth of tuning, but different decoding performance. Lastly, we provide evidence for functional convergence in GC, with neurons that can show prestimulus activity, licking-related rhythmicity and taste responses. Overall, our results demonstrate that baseline and stimulus-evoked firing profiles of GC neurons and their processing schemes change as a function of cortical layer and cell type in awake mice.SIGNIFICANCE STATEMENT Sensory cortical areas show a laminar structure, with each layer composed of distinct cell types embedded in different circuits. While studies in other primary sensory areas have elucidated that pyramidal and inhibitory neurons belonging to distinct layers show distinct response properties, whether and how response properties of gustatory cortex (GC) neurons change as a function of their laminar position and cell type remains uninvestigated. Here, we show that there are several notable differences in baseline, prestimulus, and stimulus-evoked response profiles of pyramidal and inhibitory neurons belonging to deep and superficial layers of GC.

Cortical processing of chemosensory and hedonic features of taste in active licking mice.

In the last two decades, a considerable amount of work has been devoted to investigating the neural processing and dynamics of the primary taste cortex of rats. Surprisingly, much less information is available on cortical taste electrophysiology in awake mice, an animal model that is taking on a more prominent role in taste research. Here we present electrophysiological evidence demonstrating how the gustatory cortex (GC) encodes the basic taste qualities (sweet, salty, sour, and bitter) and water when stimuli are actively sampled through licking, the stereotyped behavior by which mice control the access of fluids in the mouth. Mice were trained to receive each stimulus on a fixed ratio schedule in which they had to lick a dry spout six times to receive a tastant on the seventh lick. Electrophysiological recordings confirmed that GC neurons encode both chemosensory and hedonic aspects of actively sampled tastants. In addition, our data revealed two other main findings: GC neurons rapidly encode information about taste qualities in as little as 120 ms, and nearly half of the recorded neurons exhibit spiking activity entrained to licking at rates up to 8 Hz. Overall, our results highlight how the GC of active licking mice rapidly encodes information about taste qualities as well as ongoing sampling behavior, expanding our knowledge on cortical taste processing.NEW & NOTEWORTHY Relatively little information is available on the neural dynamics of taste processing in the mouse gustatory cortex (GC). In this study we investigate how the GC encodes chemosensory and palatability features of a wide panel of gustatory stimuli when actively sampled through licking. Our results show that GC neurons broadly encode basic taste qualities but also process taste hedonics and licking information in a temporally dynamic manner.

Synaptic Integration of Thalamic and Limbic Inputs in Rodent Gustatory Cortex.

Neurons in the gustatory cortex (GC) process multiple aspects of a tasting experience, encoding not only the physiochemical identity of tastes, but also their anticipation and hedonic value. Information pertaining to these stimulus features is relayed to GC via the gustatory thalamus (VPMpc) and basolateral amygdala (BLA). It is not known whether these inputs drive separate groups of neurons, thus activating separate channels of information, or are integrated by neurons that receive both afferents. Here, we used anterograde labeling and in vivo intracellular recordings in anesthetized rats to assess the potential convergence of BLA and VPMpc inputs in GC, and to investigate the dynamics of integration of these inputs. We report substantial anatomic overlap of BLA and VPMpc axonal fields across GC, and identify a population of GC neurons receiving converging BLA and VPMpc inputs. Our data show that BLA modulates the gain of VPMpc-evoked responses in a time-dependent fashion and that this modulation is dependent on the recruitment of synaptic inhibition by both BLA and VPMpc. Our results suggest that BLA shapes cortical processing of thalamic inputs by dynamically gating the excitatory/inhibitory balance of the GC circuit.

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.

Processing of Intraoral Olfactory and Gustatory Signals in the Gustatory Cortex of Awake Rats.

Food perception and choice depend upon the concurrent processing of olfactory and gustatory signals from the mouth. The primary gustatory cortex has been proposed to integrate chemosensory stimuli; however, no study has examined the single-unit responses to intraoral odorant presentation. Here we found that neurons in gustatory cortex can respond either exclusively to tastants, exclusively to odorants, or to both (bimodal). Several differences exist between these groups' responses; notably, bimodal neurons code palatability significantly better than unimodal neurons. This group of neurons might represent a substrate for how odorants gain the quality of tastants.

Associative learning changes cross-modal representations in the gustatory cortex.

A growing body of literature has demonstrated that primary sensory cortices are not exclusively unimodal, but can respond to stimuli of different sensory modalities. However, several questions concerning the neural representation of cross-modal stimuli remain open. Indeed, it is poorly understood if cross-modal stimuli evoke unique or overlapping representations in a primary sensory cortex and whether learning can modulate these representations. Here we recorded single unit responses to auditory, visual, somatosensory, and olfactory stimuli in the gustatory cortex (GC) of alert rats before and after associative learning. We found that, in untrained rats, the majority of GC neurons were modulated by a single modality. Upon learning, both prevalence of cross-modal responsive neurons and their breadth of tuning increased, leading to a greater overlap of representations. Altogether, our results show that the gustatory cortex represents cross-modal stimuli according to their sensory identity, and that learning changes the overlap of cross-modal representations.

A whole animal-based biosensor for fast detection of bitter compounds using extracellular potentials in rat gustatory cortex

Bitterness detection has attracted increasing attention in science and industry. However, existing methods often suffer from drawbacks such as long detection time and low specificity. Mammalian gustatory systems have been acknowledged as valid chemosensing systems, and thus the potential of utilizing intact rat gustatory system is investigated in bitterness detection and screening. Rat’s gustatory cortex (GC) functions as the central processor of gustation, and GC neurons are coupled with microelectrode array under anesthesia to reduce moving artifacts. By recording extracellular potentials in GC, response patterns evoked by bitterness are widely discovered in both single neuron and neural network activities. As a result, signals are observed to carry abundant information about taste qualities within the first 4s after bitterness delivery, and the purpose of fast detection is achieved. Based on support vector machine, this biosensor can detect and recognize bitterness with an accuracy of 94.05%. Moreover, the high specificity to bitter compounds is guaranteed by single bitter responsive neuron which can generate highly specific firing patterns in spite of the existence of interference. Quantitative study also reveals that this in vivo system is sensitive enough for further applications. In conclusion, this whole animal-based biosensor is able to detect bitterness especially with strict constrains in time and provides new platform for bitterness screening with high specificity.

Sensory Cortical Activity Is Related to the Selection of a Rhythmic Motor Action Pattern.

Rats produce robust, highly distinctive orofacial rhythms in response to taste stimuli-responses that aid in the consumption of palatable tastes and the ejection of aversive tastes, and that are sourced in a multifunctional brainstem central pattern generator. Several pieces of indirect evidence suggest that primary gustatory cortex (GC) may be a part of a distributed forebrain circuit involved in the selection of particular consumption-related rhythms, although not in the production of individual mouth movements per se. Here, we performed a series of tests of this hypothesis. We first examined the temporal relationship between GC activity and orofacial behaviors by performing paired single-neuron and electromyographic recordings in awake rats. Using a trial-by-trial analysis, we found that a subset of GC neurons shows a burst of activity beginning before the transition between nondistinct and taste-specific (i.e., consumption-related) orofacial rhythms. We further showed that shifting the latency of consumption-related behavior by selective cueing has an analogous impact on the timing of GC activity. Finally, we showed the complementary result, demonstrating that optogenetic perturbation of GC activity has a modest but significant impact on the probability that a specific rhythm will be produced in response to a strongly aversive taste. GC appears to be a part of a distributed circuit that governs the selection of taste-induced orofacial rhythms. In many well studied (typically invertebrate) sensorimotor systems, top-down modulation helps motor-control regions "select" movement patterns. Here, we provide evidence that gustatory cortex (GC) may be part of the forebrain circuit that performs this function in relation to oral behaviors ("gapes") whereby a substance in the mouth is rejected as unpalatable. We show that GC palatability coding is well timed to play this role, and that the latency of these codes changes as the latency of gaping shifts with learning. We go on to show that by silencing these neurons, we can change the likelihood of gaping. These data help to break down the sensory/motor divide by showing a role for sensory cortex in the selection of motor behavior.

A Neural Mechanism of Taste Perception Modulated by Odor Information.

Taste perception is significantly affected by other sensory modalities such as vision, smell, and somatosensation. Such taste sensation elicited by integrating gustatory and other sensory information is referred to as flavor. Although experimental studies have demonstrated the characteristics of flavor perception influenced by other sensory modalities and the involved brain areas, it remains unknown how flavor emerges from the brain circuits. Of the involved brain areas, orbitofrontal cortex (OFC), as well as gustatory cortex (GC), plays a dominant role in flavor perception. We develop here a neural model of gustatory system which consists of GC and OFC networks and examine the neural mechanism of odor-induced taste perception. Using the model, we show that flavor perception is shaped by experience-dependent learning of foods with congruent taste-odor pairs, providing a unique representation of flavor through the interaction between OFC and GC neurons. Our model also shows that feedback signals from OFC to GC modulate the dynamic stability of taste attractors in GC, leading to the enhancement or suppression of taste responses by smells. Furthermore, modeling shows that spatial variability in GC activity evoked by tastants determines to what extent odor enhances congruent taste responses. The results suggest that flavor perception is deeply associated with dynamic stability of GC attractors through the interaction between GC and OFC.

Dynamic taste responses of parabrachial pontine neurons in awake rats.

The parabrachial nuclei of the pons (PbN) receive almost direct input from taste buds on the tongue and control basic taste-driven behaviors. Thus it is reasonable to hypothesize that PbN neurons might respond to tastes in a manner similar to that of peripheral receptors, i.e., that these responses might be narrow and relatively "dynamics free." On the other hand, the majority of the input to PbN descends from forebrain regions such as gustatory cortex (GC), which processes tastes with "temporal codes" in which firing reflects first the presence, then the identity, and finally the desirability of the stimulus. Therefore a reasonable alternative hypothesis is that PbN responses might be dominated by dynamics similar to those observed in GC. Here we examined simultaneously recorded single-neuron PbN (and GC) responses in awake rats receiving exposure to basic taste stimuli. We found that pontine taste responses were almost entirely confined to canonically identified taste-PbN (t-PbN). Taste-specificity was found, furthermore, to be time varying in a larger percentage of these t-PbN responses than in responses recorded from the tissue around PbN (including non-taste-PbN). Finally, these time-varying properties were a good match for those observed in simultaneously recorded GC neurons-taste-specificity appeared after an initial nonspecific burst of action potentials, and palatability emerged several hundred milliseconds later. These results suggest that the pontine taste relay is closely allied with the dynamic taste processing performed in forebrain.

A Multisensory Network for Olfactory Processing

Primary gustatory cortex (GC) is connected (both mono- and polysynaptically) to primary olfactory (piriform) cortex (PC)-connections that might be hypothesized to underlie the construction of a "flavor" percept when both gustatory and olfactory stimuli are present. Here we use multisite electrophysiology and optical inhibition of GC neurons (GCx, produced via infection with ArchT) to demonstrate that, indeed, during gustatory stimulation, taste-selective information is transmitted from GC to PC. We go on to show that these connections impact olfactory processing even in the absence of gustatory stimulation: GCx alters PC responses to olfactory stimuli presented alone, enhancing some and eliminating others, despite leaving the path from nasal epithelium to PC intact. Finally, we show the functional importance of this latter phenomenon, demonstrating that GCx renders rats unable to properly recognize odor stimuli. This sequence of findings suggests that sensory processing may be more intrinsically integrative than previously thought.

Detection and classification of tastants in vivo using a novel bioelectronic tongue in combination with brain-machine interface.

The mammalian gustatory system is acknowledged as one of the most valid chemosensing systems. The sense of taste particularly provides critical information about ingestion of toxic and noxious chemicals. Thus the potential of utilizing rats' gustatory system is investigated in detecting sapid substances. By recording electrical activities of neurons in gustatory cortex, a novel bioelectronic tongue system is developed in combination with brain-machine interface technology. Features are extracted in both spikes and local field potentials. By visualizing these features, classification is performed and the responses to different tastants can be prominently separated from each other. The results suggest that this in vivo bioelectronic tongue is capable of detecting tastants and will provide a promising platform for potential applications in evaluating palatability of food and beverages.

Encoding and tracking of outcome-specific expectancy in the gustatory cortex of alert rats.

In natural conditions, gustatory stimuli are typically expected. Anticipatory and contextual cues provide information that allows animals to predict the availability and the identity of the substance to be ingested. Recording in alert rats trained to self-administer tastants following a go signal revealed that neurons in the primary gustatory cortex (GC) can respond to anticipatory cues. These experiments were optimized to demonstrate that even the most general form of expectation can activate neurons in GC, and did not provide indications on whether cues predicting different tastants could be encoded selectively by GC neurons. Here we recorded single-neuron activity in GC of rats engaged in a task where one auditory cue predicted sucrose, while another predicted quinine. We found that GC neurons respond differentially to the two cues. Cue-selective responses develop in parallel with learning. Comparison between cue and sucrose responses revealed that cues could trigger the activation of anticipatory representations. Additional experiments showed that an expectation of sucrose leads a subset of neurons to produce sucrose-like responses even when the tastant was omitted. Altogether, the data show that primary sensory cortices can encode for cues predicting different outcomes, and that specific expectations result in the activation of anticipatory representations.

Neural dynamics in response to binary taste mixtures

Taste stimuli encountered in the natural environment are usually combinations of multiple tastants. Although a great deal is known about how neurons in the taste system respond to single taste stimuli in isolation, less is known about how the brain deals with such mixture stimuli. Here, we probe the responses of single neurons in primary gustatory cortex (GC) of awake rats to an array of taste stimuli including 100% citric acid (100 mM), 100% sodium chloride (100 mM), 100% sucrose (100 mM), and a range of binary mixtures (90/10, 70/30, 50/50, 30/70, and 10/90%). We tested for the presence of three different hypothetical response patterns: 1) responses varying monotonically as a function of concentration of sucrose (or acid) in the mixture (the "monotonic" pattern); 2) responses increasing or decreasing as a function of degree of mixture of the stimulus (the "mixture" pattern); and 3) responses that change abruptly from being similar to one pure taste to being similar the other (the "categorical" pattern). Our results demonstrate the presence of both monotonic and mixture patterns within responses of GC neurons. Specifically, further analysis (that included the presentation of 50 mM sucrose and citric acid) made it clear that mixture suppression reliably precedes a palatability-related pattern. The temporal dynamics of the emergence of the palatability-related pattern parallel the temporal dynamics of the emergence of preference behavior for the same mixtures as measured by a brief access test. We saw no evidence of categorical coding.