BEHAVIORAL AND NEUROBIOLOGICAL MECHANISMS OF PAVLOVIAN AND INSTRUMENTAL EXTINCTION LEARNING.

This article reviews the behavioral neuroscience of extinction, the phenomenon in which a behavior that has been acquired through Pavlovian or instrumental (operant) learning decreases in strength when the outcome that reinforced it is removed. Behavioral research indicates that neither Pavlovian nor operant extinction depends substantially on erasure of the original learning but instead depends on new inhibitory learning that is primarily expressed in the context in which it is learned, as exemplified by the renewal effect. Although the nature of the inhibition may differ in Pavlovian and operant extinction, in either case the decline in responding may depend on both generalization decrement and the correction of prediction error. At the neural level, Pavlovian extinction requires a tripartite neural circuit involving the amygdala, prefrontal cortex, and hippocampus. Synaptic plasticity in the amygdala is essential for extinction learning, and prefrontal cortical inhibition of amygdala neurons encoding fear memories is involved in extinction retrieval. Hippocampal-prefrontal circuits mediate fear relapse phenomena, including renewal. Instrumental extinction involves distinct ensembles in corticostriatal, striatopallidal, and striatohypothalamic circuits as well as their thalamic returns for inhibitory (extinction) and excitatory (renewal and other relapse phenomena) control over operant responding. The field has made significant progress in recent decades, although a fully integrated biobehavioral understanding still awaits.

Pavlovian Conditioning of Immunological and Neuroendocrine Functions.

The phenomenon of behaviorally conditioned immunological and neuroendocrine functions has been investigated for the past 100 yr. The observation that associative learning processes can modify peripheral immune functions was first reported and investigated by Ivan Petrovic Pavlov and his co-workers. Their work later fell into oblivion, also because so little was known about the immune system's function and even less about the underlying mechanisms of how learning, a central nervous system activity, could affect peripheral immune responses. With the employment of a taste-avoidance paradigm in rats, this phenomenon was rediscovered 45 yr ago as one of the most fascinating examples of the reciprocal functional interaction between behavior, the brain, and peripheral immune functions, and it established psychoneuroimmunology as a new research field. Relying on growing knowledge about efferent and afferent communication pathways between the brain, neuroendocrine system, primary and secondary immune organs, and immunocompetent cells, experimental animal studies demonstrate that cellular and humoral immune and neuroendocrine functions can be modulated via associative learning protocols. These (from the classical perspective) learned immune responses are clinically relevant, since they affect the development and progression of immune-related diseases and, more importantly, are also inducible in humans. The increased knowledge about the neuropsychological machinery steering learning and memory processes together with recent insight into the mechanisms mediating placebo responses provide fascinating perspectives to exploit these learned immune and neuroendocrine responses as supportive therapies, the aim being to reduce the amount of medication required, diminishing unwanted drug side effects while maximizing the therapeutic effect for the patient's benefit.

Threat Expectation Does Not Improve Perceptual Discrimination despite Causing Heightened Priority Processing in the Frontoparietal Network.

Threat cues have been widely shown to elicit increased sensory and attentional neural processing. However, whether this enhanced recruitment leads to measurable behavioral improvements in perception is still in question. Here, we adjudicate between two opposing theories: that threat cues do or do not enhance perceptual sensitivity. We created threat stimuli by pairing one direction of motion in a random dot kinematogram with an aversive sound. While in the MRI scanner, 46 subjects (both men and women) completed a cued (threat/safe/neutral) perceptual decision-making task where they indicated the perceived motion direction of each moving dot stimulus. We found strong evidence that threat cues did not increase perceptual sensitivity compared with safe and neutral cues. This lack of improvement in perceptual decision-making ability occurred despite the threat cue resulting in widespread increases in frontoparietal BOLD activity, as well as increased connectivity between the right insula and the frontoparietal network. These results call into question the intuitive claim that expectation automatically enhances our perception of threat and highlight the role of the frontoparietal network in prioritizing the processing of threat-related environmental cues.

Encoding of Predictive Associations in Human Prefrontal and Medial Temporal Neurons During Pavlovian Appetitive Conditioning.

Pavlovian conditioning is thought to involve the formation of learned associations between stimuli and values, and between stimuli and specific features of outcomes. Here, we leveraged human single neuron recordings in ventromedial prefrontal, dorsomedial frontal, hippocampus, and amygdala while patients of both sexes performed an appetitive Pavlovian conditioning task probing both stimulus-value and stimulus-stimulus associations. Ventromedial prefrontal cortex encoded predictive value along with the amygdala, and also encoded predictions about the identity of stimuli that would subsequently be presented, suggesting a role for neurons in this region in encoding predictive information beyond value. Unsigned error signals were found in dorsomedial frontal areas and hippocampus, potentially supporting learning of non-value related outcome features. Our findings implicate distinct human prefrontal and medial temporal neuronal populations in mediating predictive associations which could partially support model-based mechanisms during Pavlovian conditioning.

A unidirectional but not uniform striatal landscape of dopamine signaling for motivational stimuli.

Dopamine signals in the striatum are critical for motivated behavior. However, their regional specificity and precise information content are actively debated. Dopaminergic projections to the striatum are topographically organized. Thus, we quantified dopamine release in response to motivational stimuli and associated predictive cues in six principal striatal regions of unrestrained, behaving rats. Absolute signal size and its modulation by stimulus value and by subjective state of the animal were interregionally heterogeneous on a medial to lateral gradient. In contrast, dopamine-concentration direction of change was homogeneous across all regions: appetitive stimuli increased and aversive stimuli decreased dopamine concentration. Although cues predictive of such motivational stimuli acquired the same influence over dopamine homogeneously across all regions, dopamine-mediated prediction-error signals were restricted to the ventromedial, limbic striatum. Together, our findings demonstrate a nuanced striatal landscape of unidirectional but not uniform dopamine signals, topographically encoding distinct aspects of motivational stimuli and their prediction.

Inhibition of Dopamine Neurons Prevents Incentive Value Encoding of a Reward Cue: With Revelations from Deep Phenotyping.

The survival of an organism is dependent on its ability to respond to cues in the environment. Such cues can attain control over behavior as a function of the value ascribed to them. Some individuals have an inherent tendency to attribute reward-paired cues with incentive motivational value, or incentive salience. For these individuals, termed sign-trackers, a discrete cue that precedes reward delivery becomes attractive and desirable in its own right. Prior work suggests that the behavior of sign-trackers is dopamine-dependent, and cue-elicited dopamine in the NAc is believed to encode the incentive value of reward cues. Here we exploited the temporal resolution of optogenetics to determine whether selective inhibition of ventral tegmental area (VTA) dopamine neurons during cue presentation attenuates the propensity to sign-track. Using male tyrosine hydroxylase (TH)-Cre Long Evans rats, it was found that, under baseline conditions, ∼84% of TH-Cre rats tend to sign-track. Laser-induced inhibition of VTA dopamine neurons during cue presentation prevented the development of sign-tracking behavior, without affecting goal-tracking behavior. When laser inhibition was terminated, these same rats developed a sign-tracking response. Video analysis using DeepLabCutTM revealed that, relative to rats that received laser inhibition, rats in the control group spent more time near the location of the reward cue even when it was not present and were more likely to orient toward and approach the cue during its presentation. These findings demonstrate that cue-elicited dopamine release is critical for the attribution of incentive salience to reward cues.SIGNIFICANCE STATEMENT Activity of dopamine neurons in the ventral tegmental area (VTA) during cue presentation is necessary for the development of a sign-tracking, but not a goal-tracking, conditioned response in a Pavlovian task. We capitalized on the temporal precision of optogenetics to pair cue presentation with inhibition of VTA dopamine neurons. A detailed behavioral analysis with DeepLabCutTM revealed that cue-directed behaviors do not emerge without dopamine neuron activity in the VTA. Importantly, however, when optogenetic inhibition is lifted, cue-directed behaviors increase, and a sign-tracking response develops. These findings confirm the necessity of dopamine neuron activity in the VTA during cue presentation to encode the incentive value of reward cues.

Anticipation of Appetitive Operant Action Induces Sustained Dopamine Release in the Nucleus Accumbens.

The mesolimbic dopamine system is implicated in signaling reward-related information as well as in actions that generate rewarding outcomes. These implications are commonly investigated in either pavlovian or operant reinforcement paradigms, where only the latter requires instrumental action. To parse contributions of reward- and action-related information to dopamine signals, we directly compared the two paradigms: male rats underwent either pavlovian or operant conditioning while dopamine release was measured in the nucleus accumbens, a brain region central for processing this information. Task conditions were identical with the exception of the operant-lever response requirement. Rats in both groups released the same quantity of dopamine at the onset of the reward-predictive cue. However, only the operant-conditioning group showed a subsequent, sustained plateau in dopamine concentration throughout the entire 5 s cue presentation (preceding the required action). This dopamine ramp was unaffected by probabilistic reward delivery, occurred exclusively before operant actions, and was not related to task performance or task acquisition as it persisted throughout the 2 week daily behavioral training. Instead, the ramp flexibly increased in duration with longer cue presentation, seemingly modulating the initial cue-onset-triggered dopamine release, that is, the reward prediction error (RPE) signal, as both signal amplitude and sustainment diminished when reward timing was made more predictable. Thus, our findings suggest that RPE and action components of dopamine release can be differentiated temporally into phasic and ramping/sustained signals, respectively, where the latter depends on the former and presumably reflects the anticipation or incentivization of appetitive action, conceptually akin to motivation.SIGNIFICANCE STATEMENT It is unclear whether the components of dopamine signals that are related to reward-associated information and reward-driven approach behavior can be separated. Most studies investigating the dopamine system use either pavlovian or operant conditioning, which both involve the delivery of reward and necessitate appetitive approach behavior. Thus, used exclusively, neither paradigm can disentangle the contributions of these components to dopamine release. However, by combining both paradigms in the same study, we find that anticipation of a reward-driven operant action induces a modulation of reward-prediction-associated dopamine release, producing so-called dopamine ramps. Therefore, our findings provide new insight into dopamine ramps and suggest that dopamine signals integrate reward and appetitive action in a temporally distinguishable, yet dependent, manner.

Nucleus accumbens neurons dynamically respond to appetitive and aversive associative learning.

To survive, individuals must learn to associate cues in the environment with emotionally relevant outcomes. This association is partially mediated by the nucleus accumbens (NAc), a key brain region of the reward circuit that is mainly composed by GABAergic medium spiny neurons (MSNs), that express either dopamine receptor D1 or D2. Recent studies showed that both populations can drive reward and aversion, however, the activity of these neurons during appetitive and aversive Pavlovian conditioning remains to be determined. Here, we investigated the relevance of D1- and D2-neurons in associative learning, by measuring calcium transients with fiber photometry during appetitive and aversive Pavlovian tasks in mice. Sucrose was used as a positive valence unconditioned stimulus (US) and foot shock was used as a negative valence US. We show that during appetitive Pavlovian conditioning, D1- and D2-neurons exhibit a general increase in activity in response to the conditioned stimuli (CS). Interestingly, D1- and D2-neurons present distinct changes in activity after sucrose consumption that dynamically evolve throughout learning. During the aversive Pavlovian conditioning, D1- and D2-neurons present an increase in the activity in response to the CS and to the US (shock). Our data support a model in which D1- and D2-neurons are concurrently activated during appetitive and aversive conditioning.

Augmenting glutamatergic, but not dopaminergic, activity in the nucleus accumbens shell disrupts responding to a discrete alcohol cue in an alcohol context.

Discrete alcohol cues and contexts are relapse triggers for people with alcohol use disorder exerting particularly powerful control over behaviour when they co-occur. Here, we investigated the neural substrates subserving the capacity for alcohol-associated contexts to elevate responding to an alcohol-predictive conditioned stimulus (CS). Specifically, rats were trained in a distinct 'alcohol context' to respond by entering a fluid port during a discrete auditory CS that predicted the delivery of alcohol and were familiarized with a 'neutral context' wherein alcohol was never available. When conditioned CS responding was tested by presenting the CS without alcohol, we found that augmenting glutamatergic activity in the nucleus accumbens (NAc) shell by microinfusing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) reduced responding to an alcohol CS in an alcohol, but not neutral, context. Further, AMPA microinfusion robustly affected behaviour, attenuating the number, duration and latency of CS responses selectively in the alcohol context. Although dopaminergic inputs to the NAc shell were previously shown to be necessary for CS responding in an alcohol context, here, chemogenetic excitation of ventral tegmental area (VTA) dopamine neurons and their inputs to the NAc shell did not affect CS responding. Critically, chemogenetic excitation of VTA dopamine neurons affected feeding behaviour and elevated c-fos immunoreactivity in the VTA and NAc shell, validating the chemogenetic approach. These findings enrich our understanding of the substrates underlying Pavlovian responding for alcohol and reveal that the capacity for contexts to modulate responding to discrete alcohol cues is delicately underpinned by the NAc shell.

Independent operations of appetitive and aversive conditioning systems lead to simultaneous production of conflicting memories in an insect.

Pavlovian conditioning is a ubiquitous form of associative learning that enables animals to remember appetitive and aversive experiences. Animals possess appetitive and aversive conditioning systems that memorize and retrieve appetitive and aversive experiences. Here, we addressed a question of whether integration of competing appetitive and aversive information takes place during the encoding of the experience or during memory retrieval. We developed novel experimental procedures to address this question using crickets (Gryllus bimaculatus), which allowed selective blockade of the expression of appetitive and aversive memories by injecting octopamine and dopamine receptor antagonists. We conditioned an odour (conditioned stimulus 1, CS1) with water and then with sodium chloride solution. At 24 h after conditioning, crickets retained both appetitive and aversive memories, and the memories were integrated to produce a conditioned response (CR). Importantly, when a visual pattern (CS2) was conditioned with CS1, appetitive and aversive memories formed simultaneously. This indicates that appetitive and aversive second-order conditionings are achieved at the same time. The memories were integrated for producing a conditioned response. We conclude that appetitive and aversive conditioning systems operate independently to form parallel appetitive and aversive memories, which compete to produce learned behaviour in crickets.

The effects of extinction and an explicitly unpaired treatment on the reinforcing properties of a Pavlovian conditioned stimulus.

This series of experiments examined the effects of extinction and an explicitly unpaired treatment on the ability of a conditioned stimulus (CS) to function as a reinforcer. Rats were trained to lever press for food, exposed to pairings of a noise CS and food, and, finally, tested for their willingness to lever press for the CS in the absence of the food. Experiment 1 provided a demonstration of conditioned reinforcement (using controls that were only exposed to unpaired presentations of the CS and food) and showed that it was equivalent after one or four sessions of CS-food pairings. Experiments 2 and 3 showed that, after one session of CS-food pairings, repeated presentations of the CS alone reduced its reinforcing properties; but after four sessions of CS-food pairings, repeated presentations of the CS alone had no effect on these properties. Experiment 4 showed that, after four sessions of CS-food pairings, explicitly unpaired presentations of the CS and food completely undermined conditioned reinforcement. Finally, Experiment 5 provided within-experiment evidence that, after four sessions of CS-food pairings, the reinforcing properties of the CS were disrupted by explicitly unpaired presentations of the CS and food but spared by repeated presentations of the CS alone. Together, these findings indicate that the effectiveness of extinction in undermining the reinforcing properties of a CS depends on its level of conditioning; and that, where extinction fails to disrupt these properties, they are successfully undermined by an explicitly unpaired treatment. They are discussed with respect to findings in the literature on Pavlovian-to-instrumental transfer; and the Rescorla-Wagner model, which anticipates that an explicitly unpaired treatment will be more effective than extinction in reversing the effects of conditioning.

Cue-potentiated feeding in rodents: Implications for weight regulation in obesogenic environments.

Cue-potentiated feeding (CPF) describes instances where food intake is increased by exposure to conditioned cues associated with food, often in the absence of hunger. CPF effects have been reported in a range of experimental protocols developed by researchers working across diverse fields spanning behavioural neuroscience, social psychology and ecology. Here we review the evolution of research on cue-potentiated feeding in animal models to identify important behavioural parameters and key neural circuits and pharmacological systems underlying the effect. Overall, evidence indicates that social, discrete and contextual stimuli can be used to elicit CPF effects across multiple species, though effects are often subtle and sensitive to procedural variables. While regular exposure to food cues is thought to be a key risk factor for overeating in so-called 'obesogenic' environments, further work is needed to identify whether CPF promotes positive energy balance and weight gain over the longer term. We suggest several methodological and conceptual areas for inquiry to elucidate the contribution of CPF to the regulation of food choice and energy intake.

The effect of corticosterone on the acquisition of Pavlovian conditioned approach behavior in rats is dependent on sex and vendor.

Cues in the environment become predictors of biologically relevant stimuli, such as food, through associative learning. These cues can not only act as predictors but can also be attributed with incentive motivational value and gain control over behavior. When a cue is imbued with incentive salience, it attains the ability to elicit maladaptive behaviors characteristic of psychopathology. We can capture the propensity to attribute incentive salience to a reward cue in rats using a Pavlovian conditioned approach paradigm, in which the presentation of a discrete lever-cue is followed by the delivery of a food reward. Upon learning the cue-reward relationship, some rats, termed sign-trackers, develop a conditioned response directed towards the lever-cue; whereas others, termed goal-trackers, approach the food cup upon lever-cue presentation. Here, we assessed the effects of systemic corticosterone (CORT) on the acquisition and expression of sign- and goal-tracking behaviors in male and female rats, while examining the role of the vendor (Charles River or Taconic) from which the rats originated in these effects. Treatment naïve male and female rats from Charles River had a greater tendency to sign-track than those from Taconic. Administration of CORT enhanced the acquisition of sign-tracking behavior in males from Charles River and females from both vendors. Conversely, administration of CORT had no effect on the expression of the conditioned response. These findings demonstrate a role for CORT in cue-reward learning and suggest that inherent tendencies towards sign- or goal-tracking may interact with this physiological mediator of motivated behavior.

Conceptual-level disgust conditioning in contamination-based obsessive-compulsive disorder.

Pavlovian fear conditioning and extinction represent learning mechanisms underlying exposure-based interventions. While increasing evidence indicates a pivotal role of disgust in the development of contamination-based obsessive-compulsive disorder (C-OCD), dysregulations in conditioned disgust acquisition and maintenance, in particular driven by higher-order conceptual processes, have not been examined. Here, we address this gap by exposing individuals with high (HCC, n = 41) or low (LCC, n = 41) contamination concern to a conceptual-level disgust conditioning and extinction paradigm. Conditioned stimuli (CS+) were images from one conceptual category partially reinforced by unconditioned disgust-eliciting stimuli (US), while images from another category served as non-reinforced conditioned stimuli (CS-). Skin conductance responses (SCRs), US expectancy and CS valence ratings served as primary outcomes to quantify conditioned disgust responses. Relative to LCC, HCC individuals exhibited increased US expectancy and CS+ disgust experience, but comparable SCR levels following disgust acquisition. Despite a decrease in conditioned responses from the acquisition phase to the extinction phase, both groups did not fully extinguish the learned disgust. Importantly, the extinction resilience of acquired disgust was more pronounced in HCC individuals. Together, our findings suggest that individuals with high self-reported contamination concern exhibit increased disgust acquisition and resistance to extinction. The findings provide preliminary evidence on how dysregulated disgust learning mechanism across semantically related concepts may contribute to C-OCD.

Corticostriatal Suppression of Appetitive Pavlovian Conditioned Responding.

The capacity to suppress learned responses is essential for animals to adapt in dynamic environments. Extinction is a process by which animals learn to suppress conditioned responding when an expected outcome is omitted. The infralimbic (IL) cortex to nucleus accumbens shell (NAcS) neural circuit is implicated in suppressing conditioned responding after extinction, especially in the context of operant cocaine-seeking behavior. However, the role of the IL-to-NAcS neural circuit in the extinction of responding to appetitive Pavlovian cues is unknown, and the psychological mechanisms involved in response suppression following extinction are unclear. We trained male Long Evans rats to associate a 10 s auditory conditioned stimulus (CS; 14 trials per session) with a sucrose unconditioned stimulus (US; 0.2 ml per CS) in a specific context, and then following extinction in a different context, precipitated a renewal of CS responding by presenting the CS alone in the original Pavlovian conditioning context. Unilateral, optogenetic stimulation of the IL-to-NAcS circuit selectively during CS trials suppressed renewal. In a separate experiment, IL-to-NAcS stimulation suppressed CS responding regardless of prior extinction and impaired extinction retrieval. Finally, IL-to-NAcS stimulation during the CS did not suppress the acquisition of Pavlovian conditioning but was required for the subsequent expression of CS responding. These results are consistent with multiple studies showing that the IL-to-NAcS neural circuit is involved in the suppression of operant cocaine-seeking, extending these findings to appetitive Pavlovian cues. The suppression of appetitive Pavlovian responding following IL-to-NAcS circuit stimulation, however, does not appear to be an extinction-dependent process.SIGNIFICANCE STATEMENT Extinction is a form of inhibitory learning through which animals learn to suppress conditioned responding in the face of nonreinforcement. We investigated the role of the IL cortex inputs to the NAcS in the extinction of responding to appetitive Pavlovian cues and the psychological mechanisms involved in response suppression following extinction. Using in vivo optogenetics, we found that stimulating the IL-to-NAcS neural circuit suppressed context-induced renewal of conditioned responding after extinction. In a separate experiment, stimulating the IL-to-NAcS circuit suppressed conditioned responding in an extinction-independent manner. These findings can be used by future research aimed at understanding how corticostriatal circuits contribute to behavioral flexibility and mental disorders that involve the suppression of learned behaviors.

Optogenetic stimulation of infralimbic cortex projections to the paraventricular thalamus attenuates context-induced renewal.

Contexts associated with prior reinforcement can renew extinguished conditioned responding. The prelimbic (PL) and infralimbic (IL) cortices are thought to mediate the expression and suppression of conditioned responding, respectively. Evidence suggests that PL inputs to the paraventricular nucleus of the thalamus (PVT) drive the expression of cue-induced reinstatement of drug seeking and that IL inputs to the PVT mediate fear extinction retrieval. However, the role of these projections in renewal of appetitive Pavlovian conditioned responding is unknown. We trained male and female Long-Evans rats to associate a conditioned stimulus (CS; 10 s white noise) with delivery of a 10% sucrose unconditioned stimulus (US; .2 ml/CS) to a fluid port in a distinct context (Context A). We then extinguished responding by presenting the CS without the US in a different context (Context B). At test, rats were returned to Context A, and optogenetic stimulation was delivered to either the IL-to-PVT or PL-to-PVT pathway during CS presentations. Optically stimulating the IL-to-PVT, but not the PL-to-PVT pathway, attenuated ABA renewal of CS port entries, and this effect was similar in males and females. Further, rats self-administered optical stimulation of the IL-to-PVT but not the PL-to-PVT pathway suggesting that activation of the IL-to-PVT pathway is reinforcing. The effectiveness of optical stimulation parameters to activate neurons in the IL, PL and PVT was confirmed using Fos immunohistochemistry. These findings provide evidence for novel neural mechanisms in renewal of responding to a sucrose-predictive CS, as well as more generally in contextual processing and appetitive associative learning.

Effects of predictive and incentive value manipulation on sign- and goal-tracking behavior.

When a neutral stimulus is repeatedly paired with an appetitive reward, two different types of conditioned approach responses may develop: a sign-tracking response directed toward the neutral cue, or a goal-tracking response directed toward the location of impending reward delivery. Sign-tracking responses have been postulated to result from attribution of incentive value to conditioned cues, while goal-tracking reflects the assignment of only predictive value to the cue. We therefore hypothesized that sign-tracking rats would be more sensitive to manipulations of incentive value, while goal-tracking rats would be more responsive to changes in the predictive value of the cue. We tested sign- and goal-tracking before and after devaluation of a food reward using lithium chloride, and tested whether either response could be learned under negative contingency conditions that precluded any serendipitous reinforcement of the behavior that might support instrumental learning. We also tested the effects of blocking the predictive value of a cue using simultaneous presentation of a pre-conditioned cue. We found that sign-tracking was sensitive to outcome devaluation, while goal-tracking was not. We also confirmed that both responses are Pavlovian because they can be learned under negative contingency conditions. Goal-tracking was almost completely blocked by a pre-conditioned cue, while sign-tracking was much less sensitive to such interference. These results indicate that sign- and goal-tracking may follow different rules of reinforcement learning and suggest a need to revise current models of associative learning to account for these differences.

Roles of octopamine neurons in the vertical lobe of the mushroom body for the execution of a conditioned response in cockroaches.

Aminergic neurons mediate reward signals in mammals and insects. In crickets, we showed that blockade of synaptic transmission from octopamine neurons (OANs) impairs conditioning of an odor (conditioned stimulus, CS) with water or sucrose (unconditioned stimulus, US) and execution of a conditioned response (CR) to the CS. It has not yet been established, however, whether findings in crickets can be applied to other species of insects. In this study, we investigated the roles of OANs in conditioning of salivation, monitored by activities of salivary neurons, and in execution of the CR in cockroaches (Periplaneta americana). We showed that injection of epinastine (an OA receptor antagonist) into the head hemolymph impaired both conditioning and execution of the CR, in accordance with findings in crickets. Moreover, local injection of epinastine into the vertical lobes of the mushroom body (MB), the center for associative learning and control of the CR, impaired execution of the CR, whereas injection of epinastine into the calyces of the MB or the antennal lobes (primary olfactory centers) did not. We propose that OANs in the MB vertical lobes play critical roles in the execution of the CR in cockroaches. This is analogous to the fact that midbrain dopamine neurons govern execution of learned actions in mammals.

Why is the Rescorla-Wagner model so influential?

The influence of the Rescorla-Wagner model cannot be overestimated, despite that (1) the model does not differ much computationally from its predecessors and competitors, and (2) its shortcomings are well-known in the learning community. Here we discuss the reasons behind its widespread influence in the cognitive and neural sciences, and argue that it is the constant search for general-process theories by learning scholars which eventually produced a model whose application spans many different areas of research to this day. We focus on the theoretical and empirical background of the model, the theoretical connections that it has with later developments across Marr's levels of analysis, as well as the broad variety of research that it has guided and inspired.

Fear learning and extinction predicts anxiety in daily life: a study of Pavlovian conditioning and ecological momentary assessment.

BACKGROUND: The association between anxious mood and aberrant fear learning mechanisms has not been fully elucidated. Studying how fear conditioning and extinction constructs relate to anxiety symptoms and reactivity to stressful and benign moments in everyday life provides a powerful addition to experimental paradigms. METHOD: Fifty-one young adults completed laboratory-based differential conditioning and extinction tasks with (CS + ) and without (CS-) an aversive unconditional stimulus (US). Electrodermal skin conductance responses were measured during each phase, followed by ecological momentary assessment (EMA) tapping anxiety and stressors six times daily for seven days (2, 142 moments). RESULTS: Conditioned electrodermal reactivity to the CS + and overgeneralisation to the CS- were associated with greater change in anxiety (measured via EMA), across non-stressful situations, remaining the same across stressful situations. Likewise, during extinction when the CS + is now safe, more electrodermal reactivity to the CS + was associated with more anxiety change across non-stressful situations and remained the same across stressful situations. Also, during extinction when threat is absent, more electrodermal reactivity at the late stage of the CS- was associated with less momentary anxiety change in response to stressful situations; more electrodermal activity at the late stage of the CS + was associated with more anxiety change across non-stressful situations and remained the same across stressful situations. CONCLUSIONS: Sampling 'in vivo' emotion and stress experiences, study findings revealed links between conditioned electrodermal reactivity and overgeneralisation to safe stimuli and heightened anxious reactivity during non-stressful (i.e. safe) moments in daily life, coupled with less change in response to actual stressors.