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.

Single and population coding of taste in the gustatory cortex of awake mice.

Electrophysiological analysis has revealed much about the broad coding and neural ensemble dynamics that characterize gustatory cortical (GC) taste processing in awake rats and about how these dynamics relate to behavior. With regard to mice, however, data concerning cortical taste coding have largely been restricted to imaging, a technique that reveals average levels of neural responsiveness but that (currently) lacks the temporal sensitivity necessary for evaluation of fast response dynamics; furthermore, the few extant studies have thus far failed to provide consensus on basic features of coding. We have recorded the spiking activity of ensembles of GC neurons while presenting representatives of the basic taste modalities (sweet, salty, sour, and bitter) to awake mice. Our first central result is the identification of similarities between rat and mouse taste processing: most mouse GC neurons (~66%) responded distinctly to multiple (3-4) tastes; temporal coding analyses further reveal, for the first time, that single mouse GC neurons sequentially code taste identity and palatability, the latter responses emerging ~0.5 s after the former, with whole GC ensembles transitioning suddenly and coherently from coding taste identity to coding taste palatability. The second finding is that spatial location plays very little role in any aspect of taste responses: neither between- (anterior-posterior) nor within-mouse (dorsal-ventral) mapping revealed anatomic regions with narrow or temporally simple taste responses. These data confirm recent results showing that mouse cortical taste responses are not "gustotopic" but also go beyond these imaging results to show that mice process tastes through time.NEW & NOTEWORTHY Here, we analyzed taste-related spiking activity in awake mouse gustatory cortical (GC) neural ensembles, revealing deep similarities between mouse cortical taste processing and that repeatedly demonstrated in rat: mouse GC ensembles code multiple aspects of taste in a coarse-coded, time-varying manner that is essentially invariant across the spatial extent of GC. These data demonstrate that, contrary to some reports, cortical network processing is distributed, rather than being separated out into spatial subregion.

Inhibiting gustatory thalamus or medial amygdala has opposing effects on taste neophobia.

Taste neophobia is a feeding system defense mechanism that limits consumption of an unknown, and therefore potentially dangerous, edible until the post-ingestive consequences are experienced. We found that transient pharmacological inhibition (induced with the GABA agonists baclofen and muscimol) of the gustatory thalamus (GT; Experiment 1), but not medial amygdala (MeA; Experiment 2), during exposure to a novel saccharin solution attenuated taste neophobia. In Experiment 3 we found that inhibition of MeA neurons (induced with the chemogenetic receptor hM4DGi) enhanced the expression of taste neophobia whereas excitation of MeA neurons (with hM3DGq) had no influence of taste neophobia. Overall, these results refine the temporal involvement of the GT in the occurrence of taste neophobia and support the hypothesis that neuronal excitation in the GT is necessary for taste neophobia. Conversely, we show that chemogenetically, but not pharmacologically, inhibiting MeA neurons is sufficient to exaggerate the expression of taste neophobia.

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.

Gustatory insular cortex, aversive taste memory and taste neophobia.

Prior research indicates a role for the gustatory insular cortex (GC) in taste neophobia. Rats with lesions of the GC show much weaker avoidance to a novel and potentially dangerous taste than do neurologically intact animals. The current study used the retention of conditioned taste aversion (CTA) as a tool to determine whether the GC modulates neophobia by processing taste novelty or taste danger. The results show that GC lesions attenuate CTA retention (Experiment 1) and impair taste neophobia (Experiment 2). Given that normal CTA retention does not involve the processing of taste novelty, the pattern of results suggests that the GC is involved in taste neophobia via its function in processing the danger conveyed by a taste stimulus.

Gustatory cortex: Taste coding and decision making in one.

A new study reveals that, as mice learn a taste discrimination task, taste responses in gustatory cortex undergo plasticity such that they reflect taste identity and predict the upcoming decision in separate response epochs.

Changes in taste palatability across the estrous cycle are modulated by hypothalamic estradiol signaling.

Food intake varies across the stages of a rat's estrous cycle. It is reasonable to hypothesize that this cyclic fluctuation in consumption reflects an impact of hormones on taste palatability/preference, but evidence for this hypothesis has been mixed, and critical within-subject experiments in which rats sample multiple tastes during each of the four main estrous phases (metestrus, diestrus, proestrus, and estrus) have been scarce. Here, we assayed licking for pleasant (sucrose, NaCl, saccharin) and aversive (quinine-HCl, citric acid) tastes each day for 5-10 days while tracking rats' estrous cycles through vaginal cytology. Initial analyses confirmed the previously-described increased consumption of pleasant stimuli 24-48 hours following the time of high estradiol. A closer look, however, revealed this effect to reflect a general magnification of palatability-higher than normal preferences for pleasant tastes and lower than normal preferences for aversive tastes-during metestrus. We hypothesized that this phenomenon might be related to estradiol processing in the lateral hypothalamus (LH), and tested this hypothesis by inhibiting LH estrogen receptor activity with ICI 182,780 during tasting. Control infusions replicated the metestrus magnification of palatability pattern; ICI infusions blocked this effect as predicted, but failed to render preferences "cycle free," instead delaying the palatability magnification until diestrus. Clearly, estrous phase mediates details of taste palatability in a manner involving hypothalamic actions of estradiol; further work will be needed to explain the lack of a flat response across the cycle with hypothalamic estradiol binding inhibited, a result which perhaps suggests dynamic interplay between brain regions or hormones. Significance Statement: Consummatory behaviors are impacted by many variables, including naturally circulating hormones. While it is clear that consumption is particularly high during the stages following the high-estradiol stage of the rodent's estrous (and human menstrual) cycle, it is as of yet unclear whether this phenomenon reflects cycle stage-specific palatability (i.e., whether pleasant tastes are particularly delicious, and aversive tastes particularly disgusting, at particular phases). Here we show that palatability is indeed modulated by estrous phase, and that this effect is governed, at least in part, by the action of estradiol within the lateral hypothalamus. These findings shed light on the mechanisms underlying the adverse impact on human welfare due to irregularities observed across the otherwise cyclic menstrual process.

Anisomycin infusions in the parabrachial nucleus and taste neophobia.

To investigate whether de novo protein synthesis in the parabrachial nucleus (PBN) is required for recovery from taste neophobia, anisomycin (a protein synthesis inhibitor) was infused immediately after consumption of a novel saccharin solution (Experiment 1). Unexpectedly, this PBN treatment caused a reduction in saccharin intake. In addition, we found that the anisomycin-induced suppression of tastant intake was attenuated by prior intra-PBN infusions of lidocaine (Experiment 2). This pattern of results raises concerns about using anisomycin to investigate memory consolidation processes in the PBN. Thus, a different manipulation may be needed to examine the nature of the neuroplastic changes that occur in the PBN during taste memory formation.

Cortical taste processing evolves through benign taste exposures.

Experience impacts learning and perception. Familiarity with stimuli that later become the conditioned stimulus (CS) in a learning paradigm, for instance, reduces the strength of that learning-a fact well documented in studies of conditioned taste aversion (CTA; De la Casa & Lubow, 1995; Lubow, 1973; Lubow & Moore, 1959). Recently, we have demonstrated that even experience with "incidental" (i.e., non-CS) stimuli influences CTA learning: Long Evans rats pre-exposed to salty and/or sour tastes later learn unusually strong aversions to novel sucrose (Flores et al., 2016), and exhibit enhanced sucrose-responsiveness after learning in gustatory cortex (GC; Flores et al., 2018). These findings suggest that incidental taste exposure (TE) may change spiking responses that have been shown to underlie the processing of tastes in GC. Here, we test this hypothesis, evaluating whether GC neuron spiking responses change across 3 days of taste exposure. Our results demonstrate that the discriminability of GC ensemble taste responses increases with this familiarization. Analysis of single-neuron responses recorded across multiple sessions reveals that taste exposure not only enriches identity and palatability information in taste-evoked activity but also enhances the discriminability of even novel tastes. These findings demonstrate that "mere" familiarization with incidental episodes of tasting changes the neural spiking responses of taste processing and provides specific insight into how such TE may impact later learning. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Schottky diode fabricated on a single crystalline diamond rod.

The fabrication process of Al/diamond Schottky diodes on single crystalline diamond rods (SCDRs) was demonstrated. SCDRs of submicron diameters were obtained by etching a polished polycrystalline diamond film in oxygen plasma. The as-scratched SCDR was confirmed to be single crystalline diamond by electron diffraction measurements showing the same fuzzy spot pattern at different parts of an SCDR. Each SCDR was extracted from a grain in the polycrystalline film where the grain size served as a limit of the length of an SCDR. Al/Ti and Al metals were deposited to form ohmic and Schottky contacts, respectively. A hydrogen plasma treatment is an essential step prior to the formation of an Al/diamond Schottky contact in order to improve the device performance. The submicron scale Al/diamond Schottky diode exhibits a very high current density of 1.4 × 10(4) A cm(-2) at a forward bias (V(F)) voltage of - 3 V.

Perturbation of amygdala-cortical projections reduces ensemble coherence of palatability coding in gustatory cortex.

Taste palatability is centrally involved in consumption decisions-we ingest foods that taste good and reject those that don't. Gustatory cortex (GC) and basolateral amygdala (BLA) almost certainly work together to mediate palatability-driven behavior, but the precise nature of their interplay during taste decision-making is still unknown. To probe this issue, we discretely perturbed (with optogenetics) activity in rats' BLA→GC axons during taste deliveries. This perturbation strongly altered GC taste responses, but while the perturbation itself was tonic (2.5 s), the alterations were not-changes preferentially aligned with the onset times of previously-described taste response epochs, and reduced evidence of palatability-related activity in the 'late-epoch' of the responses without reducing the amount of taste identity information available in the 'middle epoch.' Finally, BLA→GC perturbations changed behavior-linked taste response dynamics themselves, distinctively diminishing the abruptness of ensemble transitions into the late epoch. These results suggest that BLA 'organizes' behavior-related GC taste dynamics.

The function of groups of neurons changes from moment to moment.

Modern techniques that enable identification and targeted manipulation of neuron groups are frequently used to bolster theories that attribute specific behavioral functions to specific neuron types. These same techniques can also be used, however, to highlight limitations of such attribution, and to develop the argument that the question "what is the function of these neurons?" is ill-posed in the absence of temporal and network constraints. Here we do this, first reviewing evidence that neural responses are dynamic at multiple time scales, making the point that such changes in firing rates imply changes in what the neuron is doing. Studies involving brief perturbations of neural populations confirm this point, showing that the functions in which these populations participate change across seconds and even milliseconds. Based on these studies, we suggest that it is inappropriate to assign function to sets of neurons without contextualizing that assignment to specific times and network conditions.

Deletion of Stk11 and Fos in mouse BLA projection neurons alters intrinsic excitability and impairs formation of long-term aversive memory.

Conditioned taste aversion (CTA) is a form of one-trial learning dependent on basolateral amygdala projection neurons (BLApn). Its underlying cellular and molecular mechanisms remain poorly understood. RNAseq from BLApn identified changes in multiple candidate learning-related transcripts including the expected immediate early gene Fos and Stk11, a master kinase of the AMP-related kinase pathway with important roles in growth, metabolism and development, but not previously implicated in learning. Deletion of Stk11 in BLApn blocked memory prior to training, but not following it and increased neuronal excitability. Conversely, BLApn had reduced excitability following CTA. BLApn knockout of a second learning-related gene, Fos, also increased excitability and impaired learning. Independently increasing BLApn excitability chemogenetically during CTA also impaired memory. STK11 and C-FOS activation were independent of one another. These data suggest key roles for Stk11 and Fos in CTA long-term memory formation, dependent at least partly through convergent action on BLApn intrinsic excitability.

Anesthesia-inducing drugs also induce conditioned taste aversions.

Animals learn to reduce their intake of a tastant when its ingestion is followed by the administration of an anesthesia-inducing drug. To determine the nature of this intake suppression, the current study examined whether ketamine/xylazine (Experiment 1) and pentobarbital (Experiment 2) also conditionally reduce taste palatability. Using lick pattern analysis, we found that pairing saccharin with either drug reduced total licks, lick cluster size, and initial lick rate. Given that both lick cluster size and initial lick rate are indices of palatability, this pattern of results indicates that anesthesia-inducing drugs also induce conditioned taste aversions.

Conditioned taste aversions: From poisons to pain to drugs of abuse.

Learning what to eat and what not to eat is fundamental to our well-being, quality of life, and survival. In particular, the acquisition of conditioned taste aversions (CTAs) protects all animals (including humans) against ingesting foods that contain poisons or toxins. Counterintuitively, CTAs can also develop in situations in which we know with absolute certainty that the food did not cause the subsequent aversive systemic effect. Recent nonhuman animal research, analyzing palatability shifts, has indicated that a wider range of stimuli than has been traditionally acknowledged can induce CTAs. This article integrates these new findings with a reappraisal of some known characteristics of CTA and presents a novel conceptual analysis that is broader and more comprehensive than previous accounts of CTA learning.

Lactose malabsorption and taste aversion learning.

Consumption of foods can be suppressed by two feeding system defense mechanisms: conditioned taste aversion (CTA) or taste avoidance learning (TAL). There is a debate in the literature about which form of intake suppression is caused by various aversive stimuli. For instance, illness-inducing stimuli like lithium chloride are the gold standard for producing CTA and external (or peripheral) painful stimuli, such as footshock, are the traditional model of TAL. The distinction between CTA and TAL, which have identical effects on intake, is based on differential effects on palatability. That is, CTA involves a decrease in both intake and palatability, whereas TAL suppresses intake without influencing palatability. We evaluated whether lactose, which causes gastrointestinal pain in adult rats, produces CTA or TAL. Using lick pattern analysis to simultaneously measure intake and palatability (i.e., lick cluster size and initial lick rate), we found that pairing saccharin with intragastric infusions of lactose suppressed both the intake and palatability of saccharin. These results support the conclusion that gastrointestinal pain produced by lactose malabsorption produces a CTA, not TAL as had previously been suggested. Furthermore, these findings encourage the view that the CTA mechanism is broadly tuned to defend against the ingestion of foods with aversive post-ingestive effects.

The role of catecholamines in retention performance of a partially baited radial eight-arm maze for rats.

To assess the possible involvement of catecholaminergic neurotransmitters in maintenance of spatial cognition, the present work investigated the effects of dopaminergic and noradrenergic receptor antagonists on memory performance of rats in a partially baited radial eight-arm maze. Food-deprived rats were first trained to enter the arms baited with chocolate, and each subject was then randomly assigned to receive further training in either a place version or a cue version of the task. A specific pattern with four arms being baited was used throughout experimentation as the procedure for the place task; whereas four randomly chosen arms, each cued with a piece of sandpaper on the arm entrance, were baited from trial to trial as the procedure of the cue task. For drug evaluation, well-trained subjects were challenged with systemic injections of SCH23390, spiperone, haloperidol, prazosin, yohimbine, and propranolol. Regarding the place task, SCH23390, haloperidol, and propranolol, but not the other three drugs, significantly impaired behavioral performance by increasing the number of arm entries as well as the time to complete the task. The accuracy of performance as measured by the number of entries on the cue task was not significantly affected by any of these drugs tested. However, the times to complete the cue task were significantly increased with all drugs except yohimbine. These data show that blocking different catecholaminergic receptor subtypes produced distinct deficit patterns on the retention performance in a partially baited radial eight-arm maze. Evidently, both D1 and D2 dopamine receptors as well as beta noradrenergic receptors are important in expression of spatial memory.

Conditioned taste aversion, drugs of abuse and palatability.

We consider conditioned taste aversion to involve a learned reduction in the palatability of a taste (and hence in amount consumed) based on the association that develops when a taste experience is followed by gastrointestinal malaise. The present article evaluates the well-established finding that drugs of abuse, at doses that are otherwise considered rewarding and self-administered, cause intake suppression. Our recent work using lick pattern analysis shows that drugs of abuse also cause a palatability downshift and, therefore, support conditioned taste aversion learning.

Reduced palatability in pain-induced conditioned taste aversions.

The current study investigated whether internal pain-inducing agents can modulate palatability of a tastant in the same way as illness-inducing agents (e.g., lithium chloride). Similar to traditional conditioned taste aversion (CTA) experiments, during conditioning the rats were exposed to a saccharin solution followed by intraperitoneal injections of either gallamine (Experiment 1) or hypertonic sodium chloride (NaCl; Experiments 1 and 2). In addition to the total amount consumed, the time of each lick was recorded for lick pattern analysis. The results showed that both gallamine and hypertonic NaCl caused suppression in saccharin intake. Importantly, both lick cluster size and initial lick rate (the measures of taste palatability) were reduced as well. This pattern of results suggests that these pain-inducing agents reduce the hedonic value of the associated tastant and thus CTA is acquired. The current finding serves as evidence supporting the view that CTA is a broadly tuned mechanism that can be triggered by changes in internal body states following consummatory experience.

Amygdala-gustatory insular cortex connections and taste neophobia.

To examine whether communication between the amygdala and gustatory insular cortex (GC) is required for normal performance of taste neophobia, three experiments were conducted. In Experiment 1, rats with asymmetric unilateral lesions of the basolateral amygdala (BLA) and the GC displayed elevated intake of a novel saccharin solution relative to control subjects. However, an attenuation of neophobia was not found following asymmetric unilateral lesions of the GC and medial amygdala (MeA; Experiment 2) or of the MeA and BLA (Experiment 3). This pattern of results indicates that the BLA and GC functionally interact during expression of taste neophobia and that the MeA functionally interacts with neither the BLA nor the GC. Research is needed to further characterize the nature of the involvement of the MeA in taste neophobia and to determine the function of the BLA-GC interaction during exposure to a new taste.