Search

Rationale: The importance of reward-associated cues in eliciting behavior is well established, with stimuliassociated with drugs of abuse known to play a crucial role in recidivism. Recently, Redish (2004) proposed that drugs,acting as unconditional stimuli (US), remain associable even after being fully predicted by a conditional stimulus (CS),meaning that they are not susceptible to the blocking effect [1]; if correct, this may represent a possible mechanism toexplain exaggerated cue-controlled drug-seeking and reinstatement in nicotine dependence and substance dependenceproblems in general.Objectives: We tested whether pairings between nicotine and an environmental CS would convey conditionedreinforcement properties onto the CS, even when nicotine’s rewarding effects were already fully predicted by another cue(whether there was an absence of the blocking effect).Methods: 134 male Long-Evans rats were implanted with jugular catheters and assigned to either food- or nicotine-reward(0.06 mg/kg/inf) conditions. Each group was exposed to paired or unpaired presentations of their respective reward withone CS in 10 daily sessions; subsequently, they were exposed to 4 more daily sessions of paired presentations of thereward paired with a compound CS composed of the original CS and a second CS. Tests of the conditioned reinforcingvalue of both CSs using the active-lever-presses to total-presses ratio as an outcome were conducted following training.Results: Pressing for a blocked second CS (µ = 0.59, SD = 0.21) was significantly lower than pressing for an unblockedsecond CS (µ = 0.69, SD = 0.14) in the food-reward condition, but not in nicotine-rewarded animals, verifying thehypothesis that nicotine, but not food, is resilient to the blocking effect.Conclusion: The absence of blocking when nicotine is the reward may explain the powerful role for cues in supportingtobacco dependenceby allowing for the extension of nicotine’s rewarding value across numerous associated cues.acting as unconditional stimuli (US), remain associable even after being fully predicted by a conditional stimulus (CS),meaning that they are not susceptible to the blocking effect [1]; if correct, this may represent a possible mechanism toexplain exaggerated cue-controlled drug-seeking and reinstatement in nicotine dependence and substance dependenceproblems in general.

Basolateral amygdala (BLA) neurons are engaged by emotionally salient stimuli. An area of increasing interest is how BLA dynamics relate to evolving reward-seeking behavior, especially under situations of uncertainty or ambiguity. Here, we recorded the activity of individual BLA neurons in male rats across the acquisition and extinction of conditioned reward seeking. We assessed ongoing neural dynamics in a task where long reward cue presentations preceded an unpredictable, variably time reward delivery. We found that, with training, BLA neurons discriminated the CS+ and CS- cues with sustained cue-evoked activity that correlated with behavior and terminated only after reward receipt. BLA neurons were bidirectionally modulated, with a majority showing prolonged inhibition during cued reward seeking. Strikingly, population-level analyses revealed that neurons showing cue-evoked inhibitions and those showing excitations similarly represented the CS+ and behavioral state. This sustained population code rapidly extinguished in parallel with conditioned behavior. We next assessed the contribution of the orbitofrontal cortex (OFC), amajor reciprocal partner to the BLA. Inactivation of the OFC while simultaneously recording in the BLA revealed a blunting of sustained cue-evoked activity in the BLA that accompanied reduced reward seeking. Optogenetic disruption of BLA activity and OFC terminals in the BLA also reduced reward seeking. Our data indicate that the BLA represents reward-seeking states via sustained, bidirectional cue-driven neural encoding. This code is regulated by cortical input and is important for the maintenance of vigilant reward-seeking behavior. [ABSTRACT FROM AUTHOR]

Cues paired with alcohol can be potent drivers of craving, alcohol-seeking, consumption, and relapse. While the ventral pallidum is implicated in appetitive and consummatory responses across several reward classes and types of behaviors, its role in behavioral responses to Pavlovian alcohol cues has not previously been established. Here, we tested the impact of optogenetic inhibition of ventral pallidum on Pavlovian-conditioned alcohol-seeking in male Long Evans rats. Rats underwent Pavlovian conditioning with an auditory cue predicting alcohol delivery to a reward port and a control cue predicting no alcohol delivery, until they consistently entered the reward port more during the alcohol cue than the control cue. We then tested the within-session effects of optogenetic inhibition during 50 % of cue presentations. We found that optogenetic inhibition of ventral pallidum during the alcohol cue reduced port entry likelihood and time spent in the port, and increased port entry latency. Overall, these results suggest that normal ventral pallidum activity is necessary for Pavlovian alcohol-seeking.

Background: Sensitivity to the adverse post‐ingestive effects of ethanol likely serves as a deterrent to initiate alcohol consumption early in drinking and later may contribute to efforts to remain abstinent. Administering ethanol to naïve rats prior to Pavlovian conditioning procedures elicits robust ethanol‐conditioned taste and place avoidance (CTA; CPA) mediated by its subjective interoceptive properties. The insular cortex (IC) has been implicated as a region involved in mediating sensitivity to the interoceptive properties of ethanol. Here, we examined whether bilateral lesions of the IC affect the acquisition and expression of taste and place avoidance in ethanol‐induced CTA and CPA paradigms. Methods: Adult male and female Wistar rats received bilateral excitotoxic lesions (ibotenic acid; 20 mg/mL; 0.3 μL) of the IC prior to conditioning procedures. Subsequently, rats were conditioned to associate a novel taste stimulus (0.1% saccharin) and context with the effects of ethanol (1.0 g/kg) in a combined CTA/CPP procedure. Conditioning occurred over 8 alternating CS+/CS− days, followed by tests for expression of taste and place preferences. Data from IC‐lesioned rats were compared with neurologically intact rats. Results: Our findings revealed that neurologically intact rats showed a significantly stronger ethanol‐induced CTA than IC‐lesioned rats. There were no significant differences in total fluid intake when rats consumed water (CS−). As with CTA effects, intact rats showed a strong CPA, marked by a greater reduction in time spent on the drug‐paired context, while IC‐lesioned rats failed to display CPA to ethanol. Conclusion: These results indicate that proper IC functioning is necessary for responding to the adverse interoceptive properties of ethanol regardless of which Pavlovian paradigm is used to assess interoceptive responsivity to ethanol. Blunted IC functioning from chronic ethanol use may reduce interoceptive signaling specifically of ethanol's adverse effects thus contributing to increased alcohol use. [ABSTRACT FROM AUTHOR]

"Pavlovian" or "motivational" biases describe the phenomenon that the valence of prospective outcomes modulates action invigoration: Reward prospect invigorates action, whereas punishment prospect suppresses it. The adaptive role of these biases in decision-making is still unclear. One idea is that they constitute a fast-and-frugal decision strategy in situations characterized by high arousal, e.g., in presence of a predator, which demand a quick response. In this pre-registered study (N = 35), we tested whether such a situation—induced via subliminally presented angry versus neutral faces—leads to increased reliance on Pavlovian biases. We measured trial-by-trial arousal by tracking pupil diameter while participants performed an orthogonalized Motivational Go/NoGo Task. Pavlovian biases were present in responses, reaction times, and even gaze, with lower gaze dispersion under aversive cues reflecting "freezing of gaze." The subliminally presented faces did not affect responses, reaction times, or pupil diameter, suggesting that the arousal manipulation was ineffective. However, pupil dilations reflected facets of bias suppression, specifically the physical (but not cognitive) effort needed to overcome aversive inhibition: Particularly strong and sustained dilations occurred when participants managed to perform Go responses to aversive cues. Conversely, no such dilations occurred when they managed to inhibit responses to Win cues. These results suggest that pupil diameter does not reflect response conflict per se nor the inhibition of prepotent responses, but specifically effortful action invigoration as needed to overcome aversive inhibition. We discuss our results in the context of the "value of work" theory of striatal dopamine. [ABSTRACT FROM AUTHOR]

The modern obesogenic environment contains an abundance of food cues (e.g., sight, smell of food) as well cues that are associated with food through learning and memory processes. Food cue exposure can lead to food seeking and excessive consumption in otherwise food-sated individuals, and a high level of food cue responsivity is a risk factor for overweight and obesity. Similar food cue responses are observed in experimental rodent models, and these models are therefore useful for mechanistically identifying the neural circuits mediating food cue responsivity. This review draws from both experimental rodent models and human data to characterize the behavioral and biological processes through which food-associated stimuli contribute to overeating and weight gain. Two rodent models are emphasized - cue-potentiated feeding and Pavlovian-instrumental transfer - that provide insight in the neural circuits and peptide systems underlying food cue responsivity. Data from humans are highlighted that reveal physiological, psychological, and neural mechanisms that connect food cue responsivity with overeating and weight gain. The collective literature identifies connections between heightened food cue responsivity and obesity in both rodents and humans, and identifies underlying brain regions (nucleus accumbens, amygdala, orbitofrontal cortex, hippocampus) and endocrine systems (ghrelin) that regulate food cue responsivity in both species. These species similarities are encouraging for the possibility of mechanistic rodent model research and further human research leading to novel treatments for excessive food cue responsivity in humans.

Pavlovian fear conditioning has been extensively used to study the behavioral and neural basis of defensive systems. In a typical procedure, a cue is paired with foot shock, and subsequent cue presentation elicits freezing, a behavior theoretically linked to predator detection. Studies have since shown a fear conditioned cue can elicit locomotion, a behavior that – in addition to jumping, and rearing – is theoretically linked to imminent or occurring predation. A criticism of studies observing fear conditioned cue-elicited locomotion is that responding is non-associative. We gave rats Pavlovian fear discrimination over a baseline of reward seeking. TTL-triggered cameras captured 5 behavior frames/s around cue presentation. Experiment 1 examined the emergence of danger-specific behaviors over fear acquisition. Experiment 2 examined the expression of danger-specific behaviors in fear extinction. In total, we scored 112,000 frames for nine discrete behavior categories. Temporal ethograms show that during acquisition, a fear conditioned cue suppresses reward seeking and elicits freezing, but also elicits locomotion, jumping, and rearing – all of which are maximal when foot shock is imminent. During extinction, a fear conditioned cue most prominently suppresses reward seeking, and elicits locomotion that is timed to shock delivery. The independent expression of these behaviors in both experiments reveals a fear conditioned cue to orchestrate a temporally organized suite of behaviors.

Previous work has demonstrated the importance of the prelimbic cortex (PL) in contextual control of operant behavior. However, the associated neural circuitry responsible for providing contextual information to the PL is not well understood. In Pavlovian fear conditioning the ventral hippocampus (vH) and its projection to the PL have been shown to be important in supporting the effects of context on learning. The present experiments used chemogenetic inhibition of the direct vH-PL projection or the vH to determine involvement in expression of contextspecific operant behavior. Rats were injected with an inhibitory DREADD (hM4Di) or mCherry-only into the vH, and subsequently trained to perform a lever press response for a food pellet in a distinct context. The DREADD ligand clozapinen-oxide (CNO) was then delivered directly into the PL (experiment 1) and then systemically (experiment 2) prior to tests of the response in the training context as well as an equally familiar but untrained context. vH (systemic CNO) but not vH-PL (intra-PL CNO) inhibition was found to attenuate operant responding in its acquisition context. A third experiment, using the same rats, showed that chemogenetic inhibition of vH also reduced Pavlovian contextual fear. The present results suggest that multisynapatic connections between the vH and PL may be responsible for integration of contextual information with operant behavior. [ABSTRACT FROM AUTHOR]

In this manuscript, we report on the paramagnetic Ho2O3-based synaptic resistive random-access memory device for the implementation of neuronal functionalities such as long-term potentiation, long-term depression and spike timing dependent plasticity respectively. The plasticity of the artificial synapse is also studied by varying pulse amplitude, pulse width, and pulse interval. In addition, we could classify handwritten Modified National Institute of Standards and Technology data set (MNIST) using a fully connected neural network (FCN). The device-based FCN records a high classification accuracy of 93.47% which is comparable to the software-based test accuracy of 97.97%. This indicates the highly optimized behavior of our synaptic device for hardware neuromorphic applications. Successful emulation of Pavlovian classical conditioning for associative learning of the biological brain is achieved. We believe that the present device consists the potential to utilize in neuromorphic applications. [ABSTRACT FROM AUTHOR]

Rationale: The importance of reward-associated cues in eliciting behavior is well established, with stimuliassociated with drugs of abuse known to play a crucial role in recidivism. Recently, Redish (2004) proposed that drugs,acting as unconditional stimuli (US), remain associable even after being fully predicted by a conditional stimulus (CS),meaning that they are not susceptible to the blocking effect [1]; if correct, this may represent a possible mechanism toexplain exaggerated cue-controlled drug-seeking and reinstatement in nicotine dependence and substance dependenceproblems in general.Objectives: We tested whether pairings between nicotine and an environmental CS would convey conditionedreinforcement properties onto the CS, even when nicotine’s rewarding effects were already fully predicted by another cue(whether there was an absence of the blocking effect).Methods: 134 male Long-Evans rats were implanted with jugular catheters and assigned to either food- or nicotine-reward(0.06 mg/kg/inf) conditions. Each group was exposed to paired or unpaired presentations of their respective reward withone CS in 10 daily sessions; subsequently, they were exposed to 4 more daily sessions of paired presentations of thereward paired with a compound CS composed of the original CS and a second CS. Tests of the conditioned reinforcingvalue of both CSs using the active-lever-presses to total-presses ratio as an outcome were conducted following training.Results: Pressing for a blocked second CS (µ = 0.59, SD = 0.21) was significantly lower than pressing for an unblockedsecond CS (µ = 0.69, SD = 0.14) in the food-reward condition, but not in nicotine-rewarded animals, verifying thehypothesis that nicotine, but not food, is resilient to the blocking effect.Conclusion: The absence of blocking when nicotine is the reward may explain the powerful role for cues in supportingtobacco dependenceby allowing for the extension of nicotine’s rewarding value across numerous associated cues.acting as unconditional stimuli (US), remain associable even after being fully predicted by a conditional stimulus (CS),meaning that they are not susceptible to the blocking effect [1]; if correct, this may represent a possible mechanism toexplain exaggerated cue-controlled drug-seeking and reinstatement in nicotine dependence and substance dependenceproblems in general.

Previous work has demonstrated the importance of the prelimbic cortex (PL) in contextual control of operant behavior. However, the associated neural circuitry responsible for providing contextual information to the PL is not well understood. In Pavlovian fear conditioning the ventral hippocampus (vH) and its projection to the PL have been shown to be important in supporting the effects of context on learning. The present experiments used chemogenetic inhibition of the direct vH-PL projection or the vH to determine involvement in expression of context-specific operant behavior. Rats were injected with an inhibitory DREADD (hM4Di) or mCherry-only into the vH, and subsequently trained to perform a lever press response for a food pellet in a distinct context. The DREADD ligand clozapine-n-oxide (CNO) was then delivered directly into the PL (experiment 1) and then systemically (experiment 2) prior to tests of the response in the training context as well as an equally familiar but untrained context. vH (systemic CNO) but not vH-PL (intra-PL CNO) inhibition was found to attenuate operant responding in its acquisition context. A third experiment, using the same rats, showed that chemogenetic inhibition of vH also reduced Pavlovian contextual fear. The present results suggest that multisynapatic connections between the vH and PL may be responsible for integration of contextual information with operant behavior.

Goal-directed behavior relies on accurate mental representations of the value of expected outcomes. Disruptions to this process are a central feature of several neuropsychiatric disorders, including addiction. Goal-directed behavior is most frequently studied using instrumental paradigms paired with outcome devaluation, but cue-evoked behaviors in Pavlovian settings can also be goaldirected and therefore sensitive to changes in outcome value. Emerging literature suggests that male and female rats may differ in the degree to which their Pavlovian-conditioned responses are goal-directed, but interpretation of these findings is complicated by the tendency of female and male rats to engage in distinct types of Pavlovian responses when trained with localizable cues. Here, we used outcome devaluation via sensory-specific satiety to assess the behavioral responses in male and female Long Evans rats trained to respond to an auditory CS (conditioned stimulus) in a Pavlovian-conditioning paradigm. We found that satiety-induced devaluation led to a decrease in behavioral responding to the reward-predictive CS, with males showing an effect on both port entry latency and probability and females showing an effect only on port entry probability. Overall, our results suggest that outcome devaluation affects Pavlovian-conditioned responses in both male and female rats, but that females may be less sensitive to outcome devaluation. [ABSTRACT FROM AUTHOR]

The paper addresses the understanding of the complexity in intentional and random manipulation with deceased human bodies in the Mid-Upper Paleolithic in Eurasia. A series of single or multiple anatomic modern human burials at open air-sites, in caves or under rock shelters have been documented. Some of them are decorated and covered by extra-large sized mammal bones for protection. Beside these ritually buried individuals, isolated human cranial and postcranial fragments are scattered through the cultural and other depositional layers, many of them being identified during the post-excavation processing of faunal remains (e.g. Dolní Věstonice I, II and Pavlov I sites in the Czech Republic). These bits and pieces often lack direct evidence of predator or human manipulation (except intentionally perforated human teeth), which raises the question of a differential mortuary practice employed by our ancestors and/or the presence of specific depositional and post-depositional taphonomic conditions in the preservation of human remains. The paper addresses ethnoarcheological observations in different types of treatment of deceased human bodies among recent Arctic and sub-Arctic hunter-gatherers and reindeer herders in Eurasia with a special emphasis on the burial rites among the Nenets from northwestern Siberia. The work aims at the author's own social and economic scope, in which inappropriate or partial manipulation with the deceased human body presents a disputable, unethical and even illegal act. [ABSTRACT FROM AUTHOR]

Goal-directed behavior relies on accurate mental representations of the value of expected outcomes. Disruptions to this process are a central feature of several neuropsychiatric disorders, including addiction. Goal-directed behavior is most frequently studied using instrumental paradigms paired with outcome devaluation, but cue-evoked behaviors in Pavlovian settings can also be goal-directed and therefore sensitive to changes in outcome value. Emerging literature suggests that male and female rats may differ in the degree to which their Pavlovian-conditioned responses are goal-directed, but interpretation of these findings is complicated by the tendency of female and male rats to engage in distinct types of Pavlovian responses when trained with localizable cues. Here, we used outcome devaluation via sensory-specific satiety to assess the behavioral responses in male and female Long Evans rats trained to respond to an auditory CS (conditioned stimulus) in a Pavlovian-conditioning paradigm. We found that satiety-induced devaluation led to a decrease in behavioral responding to the reward-predictive CS, with males showing an effect on both port entry latency and probability and females showing an effect only on port entry probability. Overall, our results suggest that outcome devaluation affects Pavlovian-conditioned responses in both male and female rats, but that females may be less sensitive to outcome devaluation.

Copyright of Študijné Zvesti AU SAV is the property of Institute of Archaeology SAS and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Sign-tracking (ST) rats show enhanced cue sensitivity before drug experience that predicts greater discrete cue-induced drug seeking compared with goal-tracking or intermediate rats. Cue-evoked dopamine in the nucleus accumbens (NAc) is a neurobiological signa)ture of sign-tracking behaviors. Here, we examine a critical regulator of the dopamine system, endocannabinoids, which bind the cannabinoid receptor-1 (CB1R) in the ventral tegmental area (VTA) to control cue-evoked striatal dopamine levels. We use cell type)specific optogenetics, intra-VTA pharmacology, and fiber photometry to test the hypothesis that VTA CB1R receptor signaling regu)lates NAc dopamine levels to control sign tracking. We trained male and female rats in a Pavlovian lever autoshaping (PLA) task to determine their tracking groups before testing the effect of VTA fi NAc dopamine inhibition. We found that this circuit is critical for mediating the vigor of the ST response. Upstream of this circuit, intra-VTA infusions of rimonabant, a CB1R inverse agonist, dur)ing PLA decrease lever and increase food cup approach in sign-trackers. Using fiber photometry to measure fluorescent signals from a dopamine sensor, GRABDA (AAV9-hSyn-DA2m), we tested the effects of intra-VTA rimonabant on NAc dopamine dynamics during autoshaping in female rats. We found that intra-VTA rimonabant decreased sign-tracking behaviors, which was associated with increases in NAc shell, but not core, dopamine levels during reward delivery [unconditioned stimulus (US)]. Our results suggest that CB1R signaling in the VTA influences the balance between the conditioned stimulus-evoked and US-evoked dopamine responses in the NAc shell and biases behavioral responding to cues in sign-tracking rats. [ABSTRACT FROM AUTHOR]

A recent study by Saunders, Richard, Margolis, and Janak (2018) shows that there is a great deal left to learn about what different mesotelencephalic dopamine circuits contribute to learning about the motivational significance of reward-related cues. Their findings suggest that nigrostriatal and mesolimbic dopamine pathways support distinct reinforcement processes that independently push and pull animals toward their goals.

Rationale: The medial subregion of the orbitofrontal cortex (mOFC) is thought to play an important role representing the expected outcome of a given course of action, as lesioning or inactivating this cortical region results in the adoption of choice strategies based more on observable (rather than previously learned) information. Despite this, its role in mediating basic associative learning remains to be fully clarified. Objective: The present series of experiments examined the role of the mOFC in (1) Pavlovian conditioned approach, (2) conditioned reinforcement, (3) extinction, and (4) cue-induced reinstatement of food-seeking behavior. Methods: Separate cohorts of rats went through Pavlovian or instrumental training. Intra-mOFC infusions of either saline or GABA agonists (to temporarily inactivate neural activity) were given prior to Pavlovian approach, conditioned reinforcement, first or second day of instrumental extinction training, or cue-induced reinstatement test days. Results: mOFC inactivation increased lever-CS contacts in Pavlovian conditioned approach and (2) had no effect on conditioned reinforcement. These manipulations (3) accelerated within-session instrumental extinction during the initial extinction session, but impaired subsequent extinction learning on drug-free days. (4) mOFC inactivation induced differential effects on reinstatement that depended on baseline performance. mOFC inactivation abolished reinstatement in "Reinstater" rats (who displayed robust responding under control conditions) and robustly increased reinstatement in "Non-Reinstater" rats (who showed little reinstatement under control conditions) suggesting that individual differences in reinstatement may be supported by differences in mOFC mediated representations of expected outcomes. Conclusions: These findings have important implications for understanding how the mOFC uses stimulus-outcome and action-outcome expectancies to guide behavior, and how dysfunction within this region may contribute to pathological patterns of reward seeking. [ABSTRACT FROM AUTHOR]

Adaptive behavior in a dynamic environmental context often requires rapid revaluation of stimuli that deviates from well-learned associations. The divergence between stable value-encoding and appropriate behavioral output remains a critical component of theories of dopamine's function in learning, motivation, and motor control. Yet, how dopamine neurons are involved in the revaluation of cues when the world changes, to alter our behavior, remains unclear. Here, we make use of a complementary set of in vivo approaches to clarify the contributions of the mesolimbic dopamine system to the dynamic reorganization of reward- seeking behavior. Male and female rats were trained to discriminate when a conditioned stimulus would be followed by a sucrose reward by exploiting the prior, non-overlapping presentation of a another discrete cue-an occasion setter. Only when the occasion setter's presentation preceded the conditioned stimulus did the conditioned stimulus predict sucrose delivery, dissociating the average value of the conditioned stimulus from its immediate value, on a trial-to-trial basis. Activity of ventral tegmental area dopamine neurons was essential for rats to successfully update behavioral response to the occasion setter. Moreover, dopamine release in the nucleus accumbens following the conditioned stimulus only occurred when the occasion setter indicated it would predict reward and did not reflect its average expected value. Downstream of dopamine release, we found that neurons in the nucleus accumbens dynamically tracked the value of the conditioned stimulus. Together, these results help refine notions of dopamine function, revealing a prominent contribution of the mesolimbic dopamine system to the rapid revaluation of motivation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Reward predictive cues can selectively motivate instrumental behaviors that predict the same rewarding outcomes, an effect known as specific Pavlovian-to-instrumental transfer (PIT). This selective effect is thought to be mediated by a representation of the sensory specific properties of an outcome, that has become associated with both the Pavlovian cue and the instrumental response during initial learning. Specific satiety is a common method of outcome devaluation that reduces an outcome's value but might also lead to the habituation of the outcome's sensory properties. Previous research has demonstrated that specific PIT is insensitive to changes in specific outcome value following taste aversion devaluation, as well as general satiety manipulations, and therefore specific satiety should not disrupt specific PIT by reducing outcome value. The present rodent experiments used a specific satiety devaluation procedure immediately prior to a specific PIT test to show that habituation of these outcome specific sensory representations can disrupt its efficacy as a stimulus and abolish the specific PIT effect. Experiment 1 employed a two-lever choice test to show that a non-devalued stimulus supports specific PIT, whereas a devalued stimulus abolished the specific PIT effect. Experiment 2 replicated this procedure while controlling for response competition by using a single-lever test to confirm that a devalued stimulus abolishes the specific PIT effect. These findings demonstrate that specific satiety can disrupt the ability of an outcome specific representation to support specific PIT. Given previous findings that specific PIT is insensitive to changes in outcome value by general satiety and taste aversion devaluation, this suggests that specific satiety devaluation might disrupt the use of sensory specific outcome representations to guide behavior via a mechanism that is independent of the outcome's current value. [ABSTRACT FROM AUTHOR]

Reward predictive cues can selectively motivate instrumental behaviors that predict the same rewarding outcomes, an effect known as specific Pavlovian-to-instrumental transfer (PIT). This selective effect is thought to be mediated by a representation of the sensory specific properties of an outcome, that has become associated with both the Pavlovian cue and the instrumental response during initial learning. Specific satiety is a common method of outcome devaluation that reduces an outcome's value but might also lead to the habituation of the outcome's sensory properties. Previous research has demonstrated that specific PIT is insensitive to changes in specific outcome value following taste aversion devaluation, as well as general satiety manipulations, and therefore specific satiety should not disrupt specific PIT by reducing outcome value. The present rodent experiments used a specific satiety devaluation procedure immediately prior to a specific PIT test to show that habituation of these outcome specific sensory representations can disrupt its efficacy as a stimulus and abolish the specific PIT effect. Experiment 1 employed a two-lever choice test to show that a non-devalued stimulus supports specific PIT, whereas a devalued stimulus abolished the specific PIT effect. Experiment 2 replicated this procedure while controlling for response competition by using a single-lever test to confirm that a devalued stimulus abolishes the specific PIT effect. These findings demonstrate that specific satiety can disrupt the ability of an outcome specific representation to support specific PIT. Given previous findings that specific PIT is insensitive to changes in outcome value by general satiety and taste aversion devaluation, this suggests that specific satiety devaluation might disrupt the use of sensory specific outcome representations to guide behavior via a mechanism that is independent of the outcome's current value.

Conditioned stimuli (CS) associated with alcohol ingestion are thought to play a role in relapse by producing a craving that in turn increases motivation to drink which increases ethanol-seeking and disrupts other ongoing behavior. Alternatively, such CS may provide information indicating a likely increase in the density of the paired unconditioned stimulus and simultaneously elicit behavior that may be incompatible with other ongoing behavior, i.e., approach toward the CS. To explore these possibilities, rats were trained to respond for ethanol or food in two different components of the same session after which a light above the ethanol-lever was lighted twice during each component and each light presentation was followed by ethanol delivery. The duration of this CS was 10 s initially and then increased to 30 s, then to 100 s, and finally returned to 30 s. The change in responding for ethanol or food was compared to a matched period immediately preceding CS presentation. The CS presentation increased responding to ethanol, and this effect increases with longer CS presentations. In contrast, the CS presentation decreased responding to food, and this effect decreases with longer CS presentations. These results appear to support the informational account of CS action rather than simply a change in the motivation to seek and consume ethanol. This suggests that craving as it is commonly understood likely represents multiple behavioral processes, not simply increased desire for alcohol and that reports of craving likely reflect labeling based upon past experiences rather than a cause of future drug-taking. [ABSTRACT FROM AUTHOR]

The nucleus accumbens (NAc) core plays an important role in processing of events related to food reward, such as conditioned cues, approach or consumption. Nonetheless, there is lack of clarity regarding whether NAc core processes these separable events differently. We used the high temporal and spatial resolution of single unit recording with trial‐by‐trial video analysis to examine firing during three distinct categories termed cue, approach and consumption in a Pavlovian task. We had three goals. First, we sought to precisely define task‐related behaviour in terms of distinct phases, in order to compare neural activity between motorically matched behaviours. We found that cue‐evoked firing did not distinguish between trials on which animals initiated an approach versus ones on which they did not. Firing associated with consumption was greater than firing associated with motorically similar uncued head entry, indicating that previously reported decreases in NAc core firing during consumption relative to approach or baseline may reflect differences in motor behaviour. Secondly, we assessed changes in firing over the course of training. We found that NAc core neurons acquired a response to the tone cue within three sessions but did not change further across 10 total sessions. Thirdly, we correlated individual neuron firing during a given event with its firing during the same event on subsequent sessions. We found substantial variation in processing of cue and approach but not consumption, indicating that a given neuron may process certain events differently from session to session, while maintaining more stable processing of appetitive reward. [ABSTRACT FROM AUTHOR]

Reward-seeking actions can be guided by external cues that signal reward availability. For instance, when confronted with a stimulus that signals sugar, rats will prefer an action that produces sugar over a second action that produces grain pellets. Action selection is also sensitive to changes in the incentive value of potential rewards. Thus, rats that have been prefed a large meal of sucrose will prefer a grain-seeking action to a sucrose-seeking action. The current study investigated the dependence of these different aspects of action selection on cholinergic transmission. Hungry rats were given differential training with two unique stimulus-outcome (S1-O1 and S2-O2) and action-outcome (A1-O1 and A2-O2) contingencies during separate training phases. Rats were then given a series of Pavlovian-to-instrumental transfer tests, an assay of cue-triggered responding. Before each test, rats were injected with scopolamine (0, 0.03, or 0.1 mg/kg, intraperitoneally), a muscarinic receptor antagonist, or mecamylamine (0, 0.75, or 2.25 mg/kg, intraperitoneally), a nicotinic receptor antagonist. Although the reward-paired cues were capable of biasing action selection when rats were tested off-drug, both anticholinergic treatments were effective in disrupting this effect. During a subsequent round of outcome devaluation testing-used to assess the sensitivity of action selection to a change in reward value--we found no effect of either scopolamine or mecamylamine. These results reveal that cholinergic signaling at both muscarinic and nicotinic receptors mediates action selection based on Pavlovian reward expectations, but is not critical for flexibly selecting actions using current reward values.

Dopamine neurotransmission has been ascribed multiple functions with respect to both motivational and associative processes in reward-based learning, though these have proven difficult to tease apart. In order to better describe the role of dopamine in associative learning, this series of experiments examined the potential of dopamine D1- and D2-receptor antagonism (or combined antagonism) to influence the ability of rats to learn neutral valence stimulus-stimulus associations. Using a sensory preconditioning task, rats were first exposed to pairings of two neutral stimuli (S2-S1). Subsequently, S1 was paired with a mild foot-shock and resulting fear to both S1 (directly conditioned) and S2 (preconditioned) was examined. Initial experiments demonstrated the validity of the procedure in that measures of sensory preconditioning were shown to be contingent on pairings of the two sensory stimuli. Subsequent experiments indicated that systemic administration of dopamine D1- or D2-receptor antagonists attenuated learning when administered prior to S2-S1 pairings. However, the administration of a more generic D1R/D2R antagonist was without effect. These effects remained constant regardless of the affective valence of the conditioning environment and did not differ between male and female rats. The results are discussed in the context of recent suggestions that dopaminergic systems encode more than a simple reward prediction error, and provide potential avenues for future investigation.

Dopamine neurotransmission has been ascribed multiple functions with respect to both motivational and associative processes in reward-based learning, though these have proven difficult to tease apart. In order to better describe the role of dopamine in associative learning, this series of experiments examined the potential of dopamine D1- and D2-receptor antagonism (or combined antagonism) to influence the ability of rats to learn neutral valence stimulus-stimulus associations. Using a sensory preconditioning task, rats were first exposed to pairings of two neutral stimuli (S2-S1). Subsequently, S1 was paired with a mild foot-shock and resulting fear to both S1 (directly conditioned) and S2 (preconditioned) was examined. Initial experiments demonstrated the validity of the procedure in that measures of sensory preconditioning were shown to be contingent on pairings of the two sensory stimuli. Subsequent experiments indicated that systemic administration of dopamine D1- or D2-receptor antagonists attenuated learning when administered prior to S2-S1 pairings. However, the administration of a more generic D1R/D2R antagonist was without effect. These effects remained constant regardless of the affective valence of the conditioning environment and did not differ between male and female rats. The results are discussed in the context of recent suggestions that dopaminergic systems encode more than a simple reward prediction error, and provide potential avenues for future investigation. [ABSTRACT FROM AUTHOR]

Copyright of Študijné Zvesti AU SAV is the property of Institute of Archaeology SAS and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The orbitofrontal cortex (OFC) is a critical structure in the flexible control of value-based behaviors. OFC dysfunction is typically only detected when task or environmental contingencies change, against a backdrop of apparently intact initial acquisition and behavior. While intact acquisition following OFC lesions in simple Pavlovian cue-outcome conditioning is often predicted by models of OFC function, this predicted null effect has not been thoroughly investigated. Here, we test the effects of lesions and temporary muscimol inactivation of the rodent lateral OFC on the acquisition of a simple single cue-outcome relationship. Surprisingly, pretraining lesions significantly enhanced acquisition after overtraining, whereas post-training lesions and inactivation significantly impaired acquisition. This impaired acquisition to the cue reflects a disruption of behavioral control and not learning since the cue could also act as an effective blocking stimulus in an associative blocking procedure. These findings suggest that even simple cue-outcome representations acquired in the absence of OFC function are impoverished. Therefore, while OFC function is often associated with flexible behavioral control in complex environments, it is also involved in very simple Pavlovian acquisition where complex cue-outcome relationships are irrelevant to task performance. [ABSTRACT FROM AUTHOR]

Rationale: Checking is a functional behaviour that provides information to guide behaviour. However, in obsessive-compulsive disorder (OCD), checking may escalate to dysfunctional levels. The processes underpinning the transition from functional to dysfunctional checking are unclear but may be associated with individual differences that support the development of maladaptive behaviour. We examined one such predisposition, sign-tracking to a pavlovian conditioned stimulus, which we previously found associated with dysfunctional checking. How sign-tracking interacts with another treatment with emerging translational validity for OCD-like checking, chronic administration of the dopamine D2 receptor agonist quinpirole, is unknown. Objectives: We tested how functional and dysfunctional checking in the rat observing response task (ORT) was affected by chronic quinpirole administration in non-autoshaped controls and autoshaped animals classified as sign-trackers or goal-trackers. Methods: Sign-trackers or goal-trackers were trained on the ORT before the effects of chronic quinpirole administration on checking were assessed. Subsequently, the effects on checking of different behavioural challenges, including reward omission and the use of unpredictable reinforcement schedules, were tested. Results: Prior autoshaping increased checking. Sign-trackers and goal-trackers responded differently to quinpirole sensitization, reward omission and reinforcement uncertainty. Sign-trackers showed greater elevations in dysfunctional checking, particularly during uncertainty. By contrast, goal-trackers predominantly increased functional checking responses, possibly in response to reduced discrimination accuracy in the absence of cues signalling which lever was currently active. Conclusions: The results are discussed in terms of how pavlovian associations influence behaviour that becomes compulsive in OCD and how this may be dependent on striatal dopamine D2 receptors. [ABSTRACT FROM AUTHOR]

• Increased c-Fos expression in the lateral habenula after unpaired training. • More c-Fos–positive signals in the LHb-projecting dopaminergic midbrain of unpaired rats compared with paired rats. • LHb-lesioned animals exhibit normal performances in the paired and unpaired training. Neurons in the lateral habenula (LHb) are activated by reward omission and inhibited by reward delivery-reward processing functions opposite those of midbrain dopaminergic neurons. To further explore this, we examined the role of the LHb in associating a conditioned stimulus (CS) with the absence of an unconditioned stimulus (US) in an appetitive Pavlovian-conditioning paradigm. Rats underwent training in which a CS (light) was either paired (100% CS–US contingency) or unpaired (0% CS–US contiguity and negative contingency) with an US (food). Rats in the paired group exhibited steady acquisition of conditioned food-cup behaviors, while rats in the unpaired group showed low levels of response throughout training. After training, c-Fos levels were measured in the LHb, substantia nigra pars compacta (SNc), and ventral tegmental area (VTA) of rats in all groups. c-Fos levels were higher in the SNc/VTA of the paired group and the LHb of the unpaired group compared with the group with graded excitatory conditioning due to 50% of the CSs paired with USs and a low rate of USs presented during the intertrial interval and control groups for non-associative factors. The number of c-Fos–positive signals in LHb neurons projecting to dopaminergic midbrain neurons was higher in the unpaired group than in the paired group. Excitotoxic LHb lesions did not affect the acquisition of conditioned behaviors in the association of a CS with the presence or absence of an US. Significant increases in the numbers of c-Fos–positive neurons in the unpaired group suggest that LHb neurons engage in the process that associates a CS with the absence of an US. [ABSTRACT FROM AUTHOR]

The main features of the Shuttle Box Active Avoidance paradigm (e.g., the use of simple locomotor response as an operant and electrical current as a primary reinforcer) make this task easily automated. However, learning in this paradigm cannot be easily separated from the specificity of fear motivation. Punishment and negative reinforcement highly affect behavior in this task and complicate learning. In the present study, we describe a novel computer-controlled appetitive task in a shuttle box and compare it with active avoidance. The appetitive task was performed in the same shuttle box apparatus, additionally equipped with food dispensers in each compartment, and using a similar protocol. The reinforced reaction included the transition to the feeder in the opposite compartment in response to a stimulus. Animals mastered the appetitive task faster than the active avoidance task in the shuttle box. Other major differences between the models were the number and dynamics of intertrial responses (ITRs). Whereas in active avoidance the number of ITRs was low during learning, in the appetitive task rates were higher and they persisted throughout learning. Overall, the findings demonstrate some benefits of the appetitive task as a control condition to active avoidance: the use of a similar reaction and apparatus, no prior habituation, and fast acquisition. [ABSTRACT FROM AUTHOR]

Background: Excessive alcohol consumption produces changes in the brain that often lead to cognitive impairments. One fundamental form of learning, eyeblink classical conditioning (EBC), has been widely used to study the neurobiology of learning and memory. Participants with alcohol use disorders (AUD) have consistently shown a behavioral deficit in EBC. The present functional magnetic resonance imaging (fMRI) study is the first to examine brain function during conditioning in abstinent AUD participants and healthy participants. Methods: AUD participants met DSM‐IV criteria for alcohol dependence, had at least a 10‐year history of heavy drinking, and were abstinent from alcohol for at least 30 days. During fMRI, participants received auditory tones that predicted the occurrence of corneal airpuffs. Anticipatory eyeblink responses to these tones were monitored during the experiment to assess learning‐related changes. Results: Behavioral results indicate that AUD participants showed significant conditioning deficits and that their history of lifetime drinks corresponded to these deficits. Despite this learning impairment, AUD participants showed hyperactivation in several key cerebellar structures (including lobule VI) during conditioning. For all participants, history of lifetime drinks corresponded with their lobule VI activity. Conclusions: These findings suggest that excessive alcohol consumption is associated with abnormal cerebellar hyperactivation and conditioning impairments. [ABSTRACT FROM AUTHOR]

The endogenous opioid peptides and their receptors play important roles in Pavlovian fear conditioning in many species, including mice, rats, and humans. These roles are best viewed as regulating the conditions for fear learning by determining the actions of predictive error on association formation. Evidence will be reviewed showing such roles for opioid receptors in ventrolateral quadrant of the midbrain periaqueductal gray (vlPAG). These roles are shared across mammalian species because many of the effects of opioid receptor manipulations on fear learning first reported in rodents have now been documented in humans.

The dopamine system responds to reward-predictive cues to reflect a prospective estimation of reward value, although its role in encoding retrospective reward-related information is unclear. We report that cue-evoked dopamine release in the nucleus accumbens core encodes the time elapsed since the previous reward or rather the wait time. Specifically, a cue that always follows the preceding reward with a short wait time elicits a greater dopamine response relative to a distinct cue that always follows the preceding reward with a long wait time. Differences in the dopamine response between short wait and long wait cues were evident even when these cues were never experienced together within the same context. Conditioned responding updated accordingly with a change in cue-evoked dopamine release but was unrelated to a difference in the dopamine response between cues. Collectively, these findings illustrate that the cue-evoked dopamine response conveys a subjective estimation of the relative reward rate.

Overeating in individuals with obesity is hypothesized to be partly caused by automatic action tendencies to food cues that have the potential to override goal-directed dietary restriction. Individuals with obesity are often characterized by alterations in the processing of such rewarding food, but also of non-food stimuli, and previous research has suggested a stronger impact on the execution of goal-directed actions in obesity. Here, we investigated whether Pavlovian cues can also corrupt the learning of new approach or withdrawal behavior in individuals with obesity. We employed a probabilistic Pavlovian-instrumental learning paradigm in which participants (29 normal-weight and 29 obese) learned to actively respond (Go learning) or withhold a response (NoGo learning) in order to gain monetary rewards or avoid losses. Participants were better at learning active approach responses (Go) in the light of anticipated rewards and at learning to withhold a response (NoGo) in the light of imminent punishments. Importantly, there was no evidence for a stronger corruption of instrumental learning in individuals with obesity. Instead, they showed better learning across conditions than normal-weight participants. Using a computational reinforcement learning model, we additionally found an increased learning rate in individuals with obesity. Previous studies have mostly reported a lower reinforcement learning performance in individuals with obesity. Our results contradict this and suggest that their performance is not universally impaired: Instead, while previous studies found reduced stimulus-value learning, individuals with obesity may show better action-value learning. Our findings highlight the need for a broader investigation of behavioral adaptation in obesity across different task designs and types of reinforcement learning.

In this review article, we aim at analysing the role of stress in addiction and relapse. In order to do so, we first offer a summary of the findings from affective neuroscience trying to understand compulsive reward-seeking behaviours. These behaviours are characterised by an imbalance between the considerable amount of effort an individual is willing to mobilise to obtain a reward and the comparatively little pleasure that is felt once the reward is obtained and consumed. We illustrate how the neuropsychological mechanisms underlying these behaviours might play an important role in substance addiction and in particular for stress-induced relapse. We then review evidence suggesting that a personalised health approach would be particularly beneficial in order to better understand the role of stress in addiction and relapse in humans. More specifically, observing individual differences during distinct forms of learning (Pavlovian, habitual and goal-directed learning) might represent a very promising way to identify risk profiles for compulsive reward-seeking behaviours, addiction, and vulnerabilities to relapse under stress.

Overeating in individuals with obesity is hypothesized to be partly caused by automatic action tendencies to food cues that have the potential to override goal-directed dietary restriction. Individuals with obesity are often characterized by alterations in the processing of such rewarding food, but also of non-food stimuli, and previous research has suggested a stronger impact on the execution of goal-directed actions in obesity. Here, we investigated whether Pavlovian cues can also corrupt the learning of new approach or withdrawal behavior in individuals with obesity. We employed a probabilistic Pavlovian-instrumental learning paradigm in which participants (29 normal-weight and 29 obese) learned to actively respond (Go learning) or withhold a response (NoGo learning) in order to gain monetary rewards or avoid losses. Participants were better at learning active approach responses (Go) in the light of anticipated rewards and at learning to withhold a response (NoGo) in the light of imminent punishments. Importantly, there was no evidence for a stronger corruption of instrumental learning in individuals with obesity. Instead, they showed better learning across conditions than normal-weight participants. Using a computational reinforcement learning model, we additionally found an increased learning rate in individuals with obesity. Previous studies have mostly reported a lower reinforcement learning performance in individuals with obesity. Our results contradict this and suggest that their performance is not universally impaired: Instead, while previous studies found reduced stimulus-value learning, individuals with obesity may show better action-value learning. Our findings highlight the need for a broader investigation of behavioral adaptation in obesity across different task designs and types of reinforcement learning. [ABSTRACT FROM AUTHOR]

Nucleus accumbens dopamine plays a key role in reward‐directed approach. Past findings suggest that dopamine's role in the expression of learned behavior diminishes with extended training. However, little is known about the central substrates that mediate the shift to dopamine‐independent reward approach. In the present study, rats approached and inserted the head into a reward compartment in response to a cue signaling food delivery. On days 4 and 5 of 28‐trial‐per‐day sessions, D1 receptor antagonist R(+)‐7‐chloro‐8‐hydroxy‐3‐methyl‐1‐phenyl‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepine hydrochloride (SCH23390) infused to the NAc core reduced the probability and speed of cued approach. The disruptive effect of D1 receptor blockade was specific to the nucleus accumbens core and not seen with drug infusions to nearby dopamine target regions. In rats that received drug infusions after extended training (days 10 or 11), accumbens core D1 receptor blockade produced little effect on the expression of the same behavior. These results could have been due to a continued accumbens mediation of cued approach even after the behavior had become independent of accumbens D1 receptors. However, accumbens core ionotropic glutamate receptor blockade disrupted cued approach during early but not late stages of training, similar to the effects of D1 antagonist infusions. The results suggest that with extended training, a nucleus accumbens D1‐dependent behavior becomes less dependent not only on nucleus accumbens D1 transmission but also on excitatory transmission in the nucleus accumbens. These findings fill an important gap in a growing literature on reorganization of striatal function over the course of training. [ABSTRACT FROM AUTHOR]

This paper develops a new perspective on human-owl relations in the Pavlovian, a regional group of the early Gravettian of East-Central Europe. It argues that the regular representation of owls in figurative art and ornamentation in this context must be understood as a result of unique conditions of encounter and interaction emerging at the intersection of Southern Moravian early MIS 2-environments, Pavlovian sociocultural practice, and owl presence and behaviour. It is shown that the diverse and tree-rich environments of East-Central Europe, and the Pavlovian Hill region in particular, provided highly favourable living conditions for a rich owl community. In conjunction with Pavlovian settlement behaviour which produced large-scale aggregation sites and seems to have been associated with a more sedentary mode of life, humans were thus particularly exposed to owls that likely dominated the nightly soundscapes of the region. This coincides with the fact that many of the present owl species are resident birds and aligns with compelling evidence for a pronounced 'sense of place' in the region's early Gravettian. The paper therefore suggests considering the saliency of negotiating the owl theme in the Pavlovian as an expression of the general eco-cultural entanglement of humans and owls in this setting. I argue that human-owl relations in the Pavlovian might have ultimately been fashioned by a shared sense of place. [ABSTRACT FROM AUTHOR]

Highlights • Narrative review of extinction of avoidance methods in humans. • Operant and Pavlovian avoidance extinction has implications for clinical disorders. • Further research is needed on the validity of avoidance extinction. Abstract Avoidance is generally adaptive, yet excessive rates of avoidance can become maladaptive and lead to functional impairment and psychopathology. Laboratory-based treatment research has provided important insights about the acquisition, maintenance, and extinction of maladaptive avoidance. Despite this, laboratory research on avoidance learning and extinction in humans is relatively underdeveloped. A better understanding of avoidance extinction methods has implications for basic research with humans and the development of treatment interventions aimed at replacing maladaptive behavior with an adaptive, functional repertoire. The present article reviews, for the first time, the use of the term extinction in human research on avoidance, contrasts existing Pavlovian and operant approaches to the extinction of avoidance, considers the validity of approaches to avoidance extinction, and suggests a consistent terminology and research gaps for future translational research on anxiety and related disorders. [ABSTRACT FROM AUTHOR]

Highlights • In a serial sign-tracking paradigm (distal lever → proximal lever → food reward), animals bias responding toward the distal lever. • Previous work shows that extinction of the proximal lever leads to reduced responding toward the distal lever. • Here we show that distal lever extinction leads to reduced responding on the proximal lever. • We argue that sign-tracking levers in serial sequence share a representational association. Abstract Sign-tracking is a phenomenon whereby cues that predict rewards come to acquire their own motivational value (incentive salience) and attract appetitive behavior. Typically, sign-tracking paradigms have used single auditory, visual, or lever cues presented prior to a reward delivery. Yet, real world examples of events often can be predicted by a sequence of cues. We have shown that animals will sign-track to multiple cues presented in temporal sequence, and with time develop a bias in responding toward a reward distal cue over a reward proximal cue. Further, extinction of responding to the reward proximal cue directly decreases responding to the reward distal cue. One possible explanation of this result is that serial cues become representationally linked with one another. Here we provide further support of this by showing that extinction of responding to a reward distal cue directly reduces responding to a reward proximal cue. We suggest that the incentive salience of one cue can influence the incentive salience of the other cue. [ABSTRACT FROM AUTHOR]

The anterior cingulate cortex (ACC) responds to outcomes of a positive or negative valence, but past studies typically focus on one valence or the other, making it difficult to know how opposing valences are disambiguated. We recorded from ACC neurons as rats received tones followed by aversive, appetitive or null outcomes. The responses to the different tones/outcomes were highly inter-mixed at the single neuron level but combined to produce robust valence-specific representations at the ensemble level. The valence-specific patterns far outlasted the tones and outcomes, persisting throughout the long inter-trial intervals (ITIs) and even throughout trial blocks. When the trials were interleaved, the valence-specific patterns abruptly shifted at the start of each new trial. Overall the aversive trials had the greatest impact on the neurons. Thus within the ACC, valence-specificity is largely an emergent property of ensembles and valence-specific representations can appear quickly and persist long after the initiating event. [ABSTRACT FROM AUTHOR]