Appetitive Stimuli Research Articles

The dual-feature approach-avoidance task: validity, training efficacy, and the role of contingency awareness in changing food preference

ABSTRACT The approach-avoidance task (AAT) probes tendencies contributing to unwanted behaviours, like excessive snacking, by measuring RT differences between approach and avoidance responses to different stimuli. It retrains such tendencies using repeated avoidance of appetitive stimuli and approach of healthy alternatives. The most common paradigm, the irrelevant-feature AAT, conceals these stimulus-response contingencies by requiring approach or avoidance based on features irrelevant to the tendencies (e.g. frame colour). Unfortunately, it is an unreliable measure and not always successful as a training, likely because the stimuli can be ignored. In the novel dual-feature AAT, the combination of stimulus and irrelevant feature determines responses: participants approach foods and avoid objects surrounded by frame A, and vice versa given frame B. We trained 219 online participants to approach fruit and avoid chocolate using active (7:1 stimulus-to-frame contingency) and sham (1:1 stimulus-to-frame contingency) versions of these two trainings. Compared to sham, active irrelevant-feature training was associated with more selection and desire to eat fruit, and active dual-feature training increased approach bias for fruit. Participants’ perceived rate of approaching fruit versus chocolate correlated with many outcome measures, suggesting contingency awareness plays a major role in AAT training effectiveness, challenging implicit accounts. While the dual-feature paradigm shows potential, its high error rates, RTs, and difficulty mandate improvement.

Reward and punishment contingency shifting reveals distinct roles for VTA dopamine and GABA neurons in behavioral flexibility.

In dynamic environments where stimuli predicting rewarding or aversive outcomes unexpectedly change, it is critical to flexibly update behavior while preserving recollection of previous associations. Dopamine and GABA neurons in the ventral tegmental area (VTA) are implicated in reward and punishment learning, yet little is known about how each population adapts when the predicted outcome valence changes. We measured VTA dopamine and GABA population activity while male and female rats learned to associate three discrete auditory cues to three distinct outcomes: reward, punishment, or no outcome within the same session. After learning, the reward and punishment cue-outcome contingencies were reversed, and subsequently rereversed. As expected, the dopamine population rapidly adapted to learning and contingency reversals by increasing the response to appetitive stimuli and decreasing the response to aversive stimuli. In contrast, the GABA population increased activity to all sensory events regardless of valence, including the neutral cue. Reversing learned contingencies selectively influenced GABA responses to the reward-predictive cue, prolonging increased activity within and across sessions. The observed valence-specific dissociations in the directionality and temporal progression of VTA dopamine and GABA calcium activity indicates that these populations are independently recruited and serve distinct roles during appetitive and aversive associative learning and contingency reversal.

Inhibitory mechanisms in the prefrontal-cortex differentially mediate Putamen activity during valence-based learning.

Learning from appetitive and aversive stimuli involves interactions between the prefrontal cortex and subcortical structures. Preclinical and theoretical studies indicate that inhibition is essential in regulating the relevant neural circuitry. Here, we demonstrate that GABA, the main inhibitory neurotransmitter in the central nervous system, differentially affects how the dACC interacts with subcortical structures during appetitive and aversive learning in humans. Participants engaged in tasks involving appetitive and aversive learning, while using functional magnetic resonance spectroscopy (MRS) at 7T to track GABA concentrations in the dACC, alongside whole-brain fMRI scans to assess BOLD activation. During appetitive learning, dACC GABA concentrations were negatively correlated with learning performance and BOLD activity measured from the dACC and the Putamen. These correlations were absent during aversive learning, where dACC GABA concentrations negatively correlated with the connectivity between the dACC and the Putamen. Our results show that inhibition in the dACC mediates appetitive and aversive learning in humans through distinct mechanisms.

Examining Brain Activity Responses during Rat Ultrasonic Vocalization Playback: Insights from a Novel fMRI Translational Paradigm.

Despite decades of preclinical investigation, there remains limited understanding of the etiology and biological underpinnings of anxiety disorders. Sensitivity to potential threat is characteristic of anxiety-like behavior in humans and rodents, but traditional rodent behavioral tasks aimed to assess threat responsiveness lack translational value, especially with regard to emotionally valenced stimuli. Therefore, development of novel preclinical approaches to serve as analogues to patient assessments is needed. In humans, the fearful face task is widely used to test responsiveness to socially communicated threat signals. In rats, ultrasonic vocalizations (USVs) are analogous social cues associated with positive or negative affective states that can elicit behavioral changes in the receiver. It is therefore likely that when rats hear aversive alarm call USVs (22 kHz), they evoke translatable changes in brain activity comparable with the fearful face task. We used functional magnetic resonance imaging in male and female rats to assess changes in BOLD activity induced by exposure to aversive 22 kHz alarm calls emitted in response to threatening stimuli, prosocial (55 kHz) USVs emitted in response to appetitive stimuli, or a computer-generated 22 kHz tone. Results show patterns of regional activation that are specific to each USV stimulus. Notably, limbic regions clinically relevant to psychiatric disorders (e.g., amygdala, bed nucleus of the stria terminalis) are preferentially activated by either aversive 22 kHz or appetitive 55 kHz USVs. These results support the use of USV playback as a promising translational tool to investigate affective processing under conditions of distal threat in preclinical rat models.

Environmental enrichment enhances ethanol preference over social reward in male swiss mice: Involvement of oxytocin-dopamine interactions

The impact of environmental enrichment (EE) on natural rewards, including social and appetitive rewards, was investigated in male Swiss mice. EE, known for providing animals with various stimuli, was assessed for its effects on conditioned place preference (CPP) associated with ethanol and social stimuli. We previously demonstrated that EE increased the levels of the prosocial neuropeptide oxytocin (OT) in the hypothalamus and enhanced ethanol rewarding effects via an oxytocinergic mechanism. This study also investigated the impact of EE on social dominance and motivation for rewards, measured OT-mediated phospholipase C (PLC) activity in striatal membranes, and assessed OT expression in the hypothalamus. The role of dopamine in motivating rewards was considered, along with the interaction between OT and D1 receptors (DR) in the nucleus accumbens (NAc). Results showed that EE mice exhibited a preference for ethanol reward over social reward, a pattern replicated by the OT analogue Carbetocin. EE mice demonstrated increased social dominance and reduced motivation for appetitive taste stimuli. Higher OT mRNA levels in the hypothalamus were followed by diminished OT receptor (OTR) signaling activity in the striatum of EE mice. Additionally, EE mice displayed elevated D1R expression, which was attenuated by the OTR antagonist (L-368-889). The findings underscore the reinforcing effect of EE on ethanol and social rewards through an oxytocinergic mechanism. Nonetheless, they suggest that mechanisms other than the prosocial effect of EE may contribute to the ethanol pro-rewarding effect of EE and Carbetocin. They also point towards an OT-dopamine interaction potentially underlying some of these effects.

Mechanisms underlying food devaluation after response inhibition to food

Multiple studies reveal that a requirement to stop a response to appetitive food stimuli causes devaluation of these stimuli. However, the mechanism underlying food devaluation after stopping is still under debate. The immediate-affect theory suggests that an increase in negative affect after stopping a response is the driving force for food devaluation. A competing value-updating theory presumes that food devaluation after stopping occurs through the need to align behavior with goals. The current study assessed how food devaluation after response inhibition is influenced by negative emotional reactivity and behavior-goal alignment on a trial-by-trial basis. The study included 60 healthy participants who completed a Food-Stop-Signal-Emotion task. Participants categorized high vs. low-calorie food stimuli and stopped their response upon encountering a stop signal. Subsequently, participants made subjective negativity ratings of negative- or neutral-valenced emotional images, and rated their desire to eat the previously depicted food. In contrast to predictions made by the immediate-affect account, food devaluation after stopping was not mediated nor moderated via changes in negative emotional reactivity after stopping. In support of the value-updating account, food devaluation was modulated by behavior-goal alignment, indicated by larger food devaluation after successful vs. failed stopping. In agreement with this theory, the findings indicate that devaluation occurs more strongly when performance aligns with the task requirement. This study sheds light on the mechanism that likely underlies food devaluation after stopping. Implications regarding applied use of food-inhibition trainings are discussed.

The pharyngeal taste organ of a blood-feeding insect functions in food recognition

BackgroundObligate blood-feeding insects obtain the nutrients and water necessary to ensure survival from the vertebrate blood. The internal taste sensilla, situated in the pharynx, evaluate the suitability of the ingested food. Here, through multiple approaches, we characterized the pharyngeal organ (PO) of the hematophagous kissing bug Rhodnius prolixus to determine its role in food assessment. The PO, located antero-dorsally in the pharynx, comprises eight taste sensilla that become bathed with the incoming blood.ResultsWe showed that these taste sensilla house gustatory receptor neurons projecting their axons through the labral nerves to reach the subesophageal zone in the brain. We found that these neurons are electrically activated by relevant appetitive and aversive gustatory stimuli such as NaCl, ATP, and caffeine. Using RNA-Seq, we examined the expression of sensory-related gene families in the PO. We identified gustatory receptors, ionotropic receptors, transient receptor potential channels, pickpocket channels, opsins, takeouts, neuropeptide precursors, neuropeptide receptors, and biogenic amine receptors. RNA interference assays demonstrated that the salt-related pickpocket channel Rproppk014276 is required during feeding of an appetitive solution of NaCl and ATP.ConclusionsWe provide evidence of the role of the pharyngeal organ in food evaluation. This work shows a comprehensive characterization of a pharyngeal taste organ in a hematophagous insect.

A peripheral subepithelial network for chemotactile processing in the predatory sea slug Pleurobranchaea californica.

Many soft-bodied animals have extensive peripheral nervous systems (PNS) with significant sensory roles. One such, the sea slug Pleurobranchaea californica, uses PNS computations in its chemotactile oral veil (OV) in prey tracking, averaging olfactory stimuli across the OV to target likely source direction, or "stimulus place". This suggests a peripheral subepithelial network (SeN) interconnecting sensory sites to compute the directional average. We pursued anatomy and connectivity of previously described ciliated putative sensory cells on OV papillae. Scanning electron microscopy (SEM) confirmed paddle-shaped cilia in clusters. Anti-tubulin and phalloidin staining showed connections to branching nervelets and muscle fibers for contraction and expansion of papillae. Ciliary cell processes could not be traced into nerves, consistent with sensory transmission to CNS via secondary afferents. Anti-tyrosine hydroxylase-stained ciliated cells in clusters and revealed an at least partially dopaminergic subepithelial network interconnecting clusters near and distant, connections consistent with PNS averaging of multiple stimulated loci. Other, unidentified, SeN neurotransmitters are likely. Confirming chemotactile functions, perfusible suction electrodes recorded ciliary spiking excited by both mechanical and appetitive chemical stimuli. Stimuli induced sensory nerve spiking like that encoding stimulus place. Sensory nerve spikes and cilia cluster spikes were not identifiable as generated by the same neurons. Ciliary clusters likely drive the sensory nerve spikes via SeN, mediating appetitive and stimulus place codes to CNS. These observations may facilitate future analyses of the PNS in odor discrimination and memory, and also suggest such SeNs as potential evolutionary precursors of CNS place-coding circuitry in the segmented, skeletonized protostomes and deuterostomes.

Hypothalamic CRF neurons facilitate brain reward function

Aversive stimuli activate corticotropin-releasing factor (CRF)-expressing neurons in the paraventricular nucleus of hypothalamus (PVNCRF neurons) and other brain stress systems to facilitate avoidance behaviors. Appetitive stimuli also engage the brain stress systems, but their contributions to reward-related behaviors are less well understood. Here, we show that mice work vigorously to optically activate PVNCRF neurons in an operant chamber, indicating a reinforcing nature of these neurons. The reinforcing property of these neurons is not mediated by activation of the hypothalamic-pituitary-adrenal (HPA) axis. We found that PVNCRF neurons send direct projections to the ventral tegmental area (VTA), and selective activation of these projections induced robust self-stimulation behaviors, without activation of the HPA axis. Similar to the PVNCRF cell bodies, self-stimulation of PVNCRF-VTA projection was dramatically attenuated by systemic pretreatment of CRF receptor 1 or dopamine D1 receptor (D1R) antagonist and augmented by corticosterone synthesis inhibitor metyrapone, but not altered by dopamine D2 receptor (D2R) antagonist. Furthermore, we found that activation of PVNCRF-VTA projections increased c-Fos expression in the VTA dopamine neurons and rapidly triggered dopamine release in the nucleus accumbens (NAc), and microinfusion of D1R or D2R antagonist into the NAc decreased the self-stimulation of these projections. Together, our findings reveal an unappreciated role of PVNCRF neurons and their VTA projections in driving reward-related behaviors, independent of their core neuroendocrine functions. As activation of PVNCRF neurons is the final common path for many stress systems, our study suggests a novel mechanism underlying the positive reinforcing effect of stressful stimuli.

Precise sensorimotor control impacts reproductive fitness of C. elegans in 3D environments.

The ability of animals to sense and navigate towards relevant cues in complex and elaborate habitats is paramount for their survival and reproductive success. The nematode Caenorhabditis elegans uses a simple and elegant sensorimotor program to track odors in its environments. Whether this allows the worm to effectively navigate a complex environment and increase its evolutionary success has not been tested yet. We designed an assay to test whether C. elegans can track odors in a complex 3D environment. We then used a previously established 3D cultivation system to test whether defect in tracking odors to find food in a complex environment affected their brood size. We found that wild-type worms can accurately migrate toward a variety of odors in 3D. However, mutants of the muscarinic acetylcholine receptor GAR-3 which have a sensorimotor integration defect that results in a subtle navigational defect steering towards attractive odors, display decreased chemotaxis to the odor butanone not seen in the traditional 2D assay. We also show that the decreased ability to locate appetitive stimuli in 3D leads to reduced brood size not observed in the standard 2D culture conditions. Our study shows that mutations in genes previously overlooked in 2D conditions can have a significant impact in the natural habitat, and highlights the importance of considering the evolutionary selective pressures that have shaped the behavior, as well as the underlying genes and neural circuits.

Better together: isolation impedes memory formation for configural learning in Lymnaea stagnalis.

Social interactions play an important role in learning and memory. There is great variability in the literature regarding the effects of social isolation on cognition. Here, we investigated how memory formation was affected when Lymnaea stagnalis, our model system, were socially isolated at three different time periods: before, during or after the configural learning training procedure. Each group of snails underwent configural learning where we recorded and compared their feeding behaviour before and after the pairing of an appetitive food stimulus with predator kairomones (i.e. the training procedure). We found that isolating snails before the training procedure had no effect on their learning and memory. However, when snails were isolated either during the training procedure or immediately after the training procedure, they no longer formed memory. These data provide further insight into how isolation impacts cognitive functioning in the context of higher-order learning.

Basolateral amygdala corticotropin releasing factor receptor 2 interacts with nonmuscle myosin II to destabilize memory in males

Preclinical studies show that inhibiting the actin motor ATPase nonmuscle myosin II (NMII) with blebbistatin (Blebb) in the basolateral amgydala (BLA) depolymerizes actin, resulting in an immediate, retrieval-independent disruption of methamphetamine (METH)-associated memory in male and female adult and adolescent rodents. The effect is highly selective, as NMII inhibition has no effect in other relevant brain regions (e.g., dorsal hippocampus [dPHC], nucleus accumbens [NAc]), nor does it interfere with associations for other aversive or appetitive stimuli, including cocaine (COC). To understand the mechanisms responsible for drug specific selectivity we began by investigating, in male mice, the pharmacokinetic differences in METH and COC brain exposure . Replicating METH’s longer half-life with COC did not render the COC association susceptible to disruption by NMII inhibition. Therefore, we next assessed transcriptional differences. Comparative RNA-seq profiling in the BLA, dHPC and NAc following METH or COC conditioning identified crhr2, which encodes the corticotropin releasing factor receptor 2 (CRF2), as uniquely upregulated by METH in the BLA. CRF2 antagonism with Astressin-2B (AS2B) had no effect on METH-associated memory after consolidation, allowing for determination of CRF2 influences on NMII-based susceptibility. Pretreatment with AS2B prevented the ability of Blebb to disrupt an established METH-associated memory. Alternatively, combining CRF2 overexpression and agonist treatment, urocortin 3 (UCN3), in the BLA during conditioning rendered COC-associated memory susceptible to disruption by NMII inhibition, mimicking the Blebb-induced, retrieval-independent memory disruption seen with METH. These results suggest that BLA CRF2 receptor activation during memory formation in male mice can prevent stabilization of the actin-myosin cytoskeleton supporting the memory, rendering it vulnerable to disruption by NMII inhibition. CRF2 represents an interesting target for BLA-dependent memory destabilization via downstream effects on NMII.

Evaluation of behavioural selection processes in conflict scenarios using a newly developed mouse behavioural paradigm

Selecting an appropriate behaviour is critical for survival in conflict scenarios, wherein animals face both appetitive and aversive stimuli. Behavioural selection consists of multiple processes: (1) animals remain quiet in a safe place to avoid aversive stimuli (suspension), (2) once they decide to take risks to approach appetitive stimuli, they assess the risks (risk assessment), and (3) they act to reach the reward. However, most studies have not addressed these distinct behavioural processes separately. Here, we developed a new experimental paradigm called the three-compartment conflict task to quantitatively evaluate conflict processes. Our apparatus consisted of start, flat, and grid compartments. Mice needed to explore the grid compartment, where they might receive foot shocks while trying to obtain sucrose. Applying foot shocks increased sucrose acquisition latency in subsequent trials, reflecting elevated conflict levels throughout trials. The time spent in the start compartment and the number of retreats were determined to measure the conflict levels in suspension and risk assessment, respectively. Foot shocks increased these parameters, whereas diazepam decreased them. Our new paradigm is valuable for quantitatively evaluating distinct behavioural processes and contributes to developing effective treatments for psychiatric disorders associated with maladaptive behaviours in conflict scenarios.

Representation of rewards differing in their hedonic valence in the caudate nucleus correlates with the performance in a problem-solving task in dogs (Canis familiaris)

We have investigated dogs’ (Canis familiaris) abilities in associating different sounds with appetitive stimuli of different incentive values. The association’s establishment was first tested on family dogs (n = 20) in a problem-solving behavioural paradigm (experiment 1), then in a problem-solving behavioural paradigm as well as an fMRI study on specially trained family dogs (n = 20) (experiment 2). The aim was to show behavioural and parallel neural effects of the association formed between the two sounds and two different associated appetitive stimuli. The latency of solving the problem was considered an indicator of the motivational state. In our first experiment, where only behaviour was studied, we found that dogs were quicker in solving a problem upon hearing the sound associated with food higher in reward value, suggesting that they have successfully associated the sounds with the corresponding food value. In our second experiment, this behaviour difference was not significant. In the fMRI study, the cerebral response to the two sounds was compared both before and after the associative training. Two bilateral regions of interest were explored: the caudate nucleus and the amygdala. After the associative training, the response in the caudate nucleus was higher to the sound related to a higher reward value food than to the sound related to a lower reward value food, which difference was not present before the associative training. We found an increase in the amygdala response to both sounds after the training. In a whole-brain representational similarity analysis, we found that cerebral patterns in the caudate nucleus to the two sounds were different only after the training. Moreover, we found a positive correlation between the dissimilarity index in the caudate nucleus for activation responses to the two sounds and the difference in latencies (i.e. high reward value associated sound condition latency—low reward value associated sound condition latency) to solve the behavioural task: the bigger the difference between the conditions in latency to solve the task, the greater the difference in the neural representation of the two sounds was. In summary, family dogs’ brain activation patterns reflected their expectations based on what they learned about the relationship between two sounds and their associated appetitive stimuli.

Decision making and executive functions in problematic pornography use.

Previous research on cognitive functions in Compulsive Sexual Behavior Disorder (CSBD) and problematic pornography use (PPU) reported inconsistent findings and mostly included sexual pictures in the used tasks. The role of general executive functions and cognitive competences (without the presence of appetitive stimuli) in the context of PPU is largely unexplored. This study investigated differences between individuals with high versus low problem severity of PPU regarding decision making and executive functions. The sample of the laboratory study consisted of N = 102 male adults. Besides measures of trait impulsivity, we used standard neuropsychological tests (Trail Making Test and three-back working memory task) and an intertemporal risky choice paradigm, the Cards & Lottery Task (CLT). The results show heightened impulsivity (urgency and deficits in perseverance) in individuals with high PPU, but no differences regarding performance in the CLT and executive function tasks. The findings indicate that PPU might be associated with impulsive behavior when experiencing strong emotions (urgency) and deficient cognitive performance especially in the presence of sexual stimuli but not in general.

Blocking μ-opioid receptors attenuates reinstatement of responding to an alcohol-predictive conditioned stimulus through actions in the ventral hippocampus.

The µ-opioid system is involved in the reinstatement of responding that is immediately evoked by alcohol-predictive cues. The extent of its involvement in reinstatement observed in a new model that evaluates the delayed effects of re-exposure to alcohol, however, is unclear. The current study investigated the role of µ-opioid receptors (MORs) in the delayed reinstatement of an extinguished, Pavlovian conditioned response that was evoked 24 h after alcohol re-exposure. Female and male Long-Evans rats received Pavlovian conditioning in which a conditioned stimulus (CS) was paired with the delivery of an appetitive unconditioned stimulus (US; Experiments 1, 2, 4: 15% v/v alcohol; Experiment 3: 10% w/v sucrose) that was delivered into a fluid port for oral intake. During subsequent extinction sessions, the CS was presented as before but without the US. Next, the US was delivered but without the CS. A reinstatement test was conducted 24 h later, during which the CS was presented in the absence of the US. Silencing MORs via systemic naltrexone (0.3 or 1.0 mg/kg) attenuated reinstatement of port entries elicited by an alcohol-CS, but not those elicited by a sucrose-CS. Finally, blocking MORs in the ventral hippocampus via bilateral microinfusion of D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP; 2.5 or 5.0 µg/hemisphere) prevented reinstatement of port alcohol-CS port entries. These data show that MORs are involved in the delayed reinstatement of a Pavlovian conditioned response in an alcohol-specific manner. Importantly, these data illustrate, for the first time, that MORs in the ventral hippocampus are necessary for responding to an alcohol-predictive cue.

Five-minute exposure to a novel appetitive food substance is sufficient time for a microRNA-dependent long-term memory to form.

The Garcia effect is a unique form of conditioned taste aversion which requires that a novel food stimulus be followed sometime later by a sickness state associated with the novel food stimulus. The long-lasting associative memory resulting from the Garcia effect ensures that organisms avoid toxic foods in their environment. Considering its ecological relevance, we sought to investigate whether a brief encounter (5min) with a novel, appetitive food stimulus can cause a persisting long-term memory (LTM) to form that would in turn block the Garcia effect in Lymnaea stagnalis. Furthermore, we wanted to explore whether that persisting LTM could be modified by the alteration of microRNAs via an injection of poly-L-lysine (PLL), an inhibitor of Dicer-mediated microRNA biogenesis. The Garcia effect procedure involved two observations of feeding behavior in carrot separated by a heat stress (30°C for 1h). Exposing snails to carrot for 5min caused a LTM to form and persist for 1week, effectively preventing the Garcia effect in snails. In contrast, PLL injection following the 5-min carrot exposure impaired LTM formation, allowing the Garcia effect to occur. These results provide more insight into LTM formation and the Garcia effect, an important survival mechanism.

Parsing patterns of reward responsiveness: Initial evidence from latent profile analysis.

Variation in reward responsiveness has been linked to psychopathology. Reward responsiveness is a complex phenomenon that encompasses different temporal dimensions (i.e., reward anticipation or consumption) that can be measured using multiple appetitive stimuli. Furthermore, distinct measures, such as neural and self-report measures, reflect related but distinct aspects of reward responsiveness. To understand reward responsiveness more comprehensively and better identify deficits in reward responsiveness implicated in psychopathology, we examined ways multiple measures of reward responsiveness jointly contribute to distinct psychological problems by using latent profile analysis. Specifically, we identified three profiles of reward responsiveness among 139 female participants based on their neural responses to money, food, social acceptance, and erotic images and self-reported responsiveness to reward anticipation and consumption. Profile 1 (n = 30) exhibited blunted neural responses to social rewards and erotic images, low self-reported reward responsiveness, but average neural responses to monetary and food rewards. Profile 2 (n = 71) showed elevated neural response to monetary rewards, average neural responses to other stimuli, and average self-reported reward responsiveness. Profile 3 (n = 38) showed more variable neural responses to reward (e.g., hypersensitivity to erotic images, hyposensitivity to monetary rewards), and high self-reported reward responsiveness. These profiles were differentially associated with variables generally linked to aberrations in reward responsiveness. For example, Profile 1 was most strongly associated with anhedonic depression and social dysfunction, whereas Profile 3 was associated with risk-taking behaviors. These preliminary findings may help to elucidate ways different measures of reward responsiveness manifest within and across individuals and identify specific vulnerabilities for distinct psychological problems.

Imaging Olfactory Learning-Induced Plasticity in Vivo in the Drosophila Brain.

In vivo imaging of brain activity in Drosophila allows the dissection of numerous types of biologically important neuronal events. A common paradigm involves imaging neuronal Ca2+ transients, often in response to sensory stimuli. These Ca2+ transients correlate with neuronal spiking activity, which generates voltage-sensitive Ca2+ influx. In addition, there is a range of genetically encoded reporters of membrane voltage and of other signaling molecules, such as second-messenger signaling cascade enzymes and neurotransmitters, enabling optical access to a range of cellular processes. Moreover, sophisticated gene expression systems enable access to virtually any single neuron or neuronal group in the fly brain. The in vivo imaging approach enables the study of these processes and how they change during salient sensory-driven events such as olfactory associative learning, when an animal (fly) is presented an odor (a conditioned stimulus) paired with an unconditioned stimulus (an aversive or appetitive stimulus) and forms an associative memory of this pairing. Optical access to neuronal events in the brain allows one to image learning-induced plasticity following the formation of associative memory, dissecting the mechanisms of memory formation, maintenance, and recall.

The Human Centromedial Amygdala Contributes to Negative Prediction Error Signaling during Appetitive and Aversive Pavlovian Gustatory Learning.

Prediction error (PE) is the mismatch between a prior expectation and reality, and it lies at the core of associative learning about aversive and appetitive stimuli. Human studies on fear learning have linked the amygdala to aversive PEs. In contrast, the relationship between the amygdala and PE in appetitive settings and stimuli, unlike those that induce fear, has received less research attention. Animal studies show that the amygdala is a functionally heterogeneous structure. Nevertheless, the role of the amygdala nuclei in PE signaling remains unknown in humans. To clarify the role of two subdivisions of the human amygdala, the centromedial amygdala (CMA) and basolateral amygdala (BLA), in appetitive and aversive PE signaling, we used gustatory pavlovian learning involving eating-related naturalistic outcomes. Thirty-eight right-handed individuals (19 females) participated in the study. We found that surprise with neutral feedback when a reward is expected triggers activity within the left and right CMA. When an aversive outcome is expected, surprise with neutral feedback triggers activity only within the left CMA. Notably, the BLA was not activated by those conditions. Thus, the CMA engages in negative PE signaling during appetitive and aversive gustatory pavlovian learning, whereas the BLA is not critical for this process. In addition, PE-related activity within the left CMA during aversive learning is negatively correlated with neuroticism and positively correlated with extraversion. The findings indicate the importance of the CMA in gustatory learning when the value of outcomes changes and have implications for understanding psychological conditions that manifest perturbed processing of negative PEs.SIGNIFICANCE STATEMENT A discrepancy between a prediction and an actual outcome (PE) plays a crucial role in learning. Learning improves when an outcome is more significant than expected (positive PE) and worsens when it is smaller than expected (negative PE). We found that the negative PE during appetitive and aversive taste learning is associated with increased activity of the CMA, which suggests that the CMA controls taste learning. Our findings may have implications for understanding psychological states associated with deficient learning from negative PEs, such as obesity and addictive behaviors.