Reward-oriented Behavior Research Articles

Dopamine dynamics are dispensable for movement but promote reward responses.

Dopamine signalling modes differ in kinetics and spatial patterns of receptor activation1,2. How these modes contribute to motor function, motivation and learning has long been debated3-21. Here we show that action-potential-induced dopamine release is dispensable for movement initiation but supports reward-oriented behaviour. We generated mice with dopamine-neuron-specific knockout of the release site organizer protein RIM to disrupt action-potential-induced dopamine release. In these mice, rapid in vivo dopamine dynamics were strongly impaired, but baseline dopamine persisted and fully supported spontaneous movement. Conversely, reserpine-mediated dopamine depletion or blockade of dopamine receptors disrupted movement initiation. The dopamine precursor L-DOPA reversed reserpine-induced bradykinesia without restoring fast dopamine dynamics, a result that substantiated the conclusion that these dynamics are dispensable for movement initiation. In contrast to spontaneous movement, reward-oriented behaviour was impaired in dopamine-neuron-specific RIM knockout mice. In conditioned place preference and two-odour discrimination tasks, the mice effectively learned to distinguish the cues, which indicates that reward-based learning persists after RIM ablation. However, theperformance vigourwas reduced. During probabilistic cue-reward association, dopamine dynamics and conditioned responses assessed through anticipatory licking were disrupted. These results demonstrate that action-potential-induced dopamine release is dispensable for motor function and subsecond precision of movement initiation but promotes motivation and performance during reward-guided behaviours.

Mobilization of endocannabinoids by midbrain dopamine neurons is required for the encoding of reward prediction

Brain levels of the endocannabinoid 2-arachidonoylglycerol (2-AG) shape motivated behavior and nucleus accumbens (NAc) dopamine release. However, it is not clear whether mobilization of 2-AG specifically from midbrain dopamine neurons is necessary for dopaminergic responses to external stimuli predicting forthcoming reward. Here, we use a viral-genetic strategy to prevent the expression of the 2-AG-synthesizing enzyme diacylglycerol lipase α (DGLα) from ventral tegmental area (VTA) dopamine cells in adult mice. We find that DGLα deletion from VTA dopamine neurons prevents depolarization-induced suppression of excitation (DSE), a form of 2-AG-mediated synaptic plasticity, in dopamine neurons. DGLα deletion also decreases effortful, cue-driven reward-seeking but has no effect on non-cued or low-effort operant tasks and other behaviors. Moreover, dopamine recording in the NAc reveals that deletion of DGLα impairs the transfer of accumbal dopamine signaling from a reward to its earliest predictors. These results demonstrate that 2-AG mobilization from VTA dopamine neurons is a necessary step for the generation of dopamine-based predictive associations that are required to direct and energize reward-oriented behavior.

Region-specific involvement of ventral striatal dopamine D2 receptor-expressing medium spiny neurons in nociception

The ventrolateral striatum (VLS), a subregion of the ventral striatum (VS), possesses distinct neuronal Ca2+ activities and functions in reward-oriented behavior, compared with the ventromedial striatum (VMS) based on the anatomical feature. We hypothesized that the VLS exhibits unique neuronal activity and function in nociceptive processing, a part of aversive processing. Using fiber photometry to monitor the neuronal Ca2+ activities, we demonstrated that acute noxious mechanical stimuli like tail-pinch increased the Ca2+ activity of dopamine D2 receptor-expressing medium spiny neurons (D2-MSNs) in the VLS in correlation with the stimulus intensities in mice, whereas mechanical stimuli increased the VMS D2-MSN activity independent of the stimulus intensities. Likewise, thermal stimuli decreased the VLS and VMS D2-MSN Ca2+ activities during nociceptive behaviors in the hot plate test. Furthermore, the VLS D2-MSNs increased their Ca2+ activity accompanied by formalin-induced nociceptive behaviors in mice, whereas the VMS D2-MSNs decreased it. The optogenetic inhibition of VLS D2-MSN activity increased the formalin-induced pain-related behavior in mice, thus suggesting the inhibitory effect of VLS D2-MSN activity on chemical nociceptive behavior, in contrast to previous reports that the VMS D2-MSNs could not involve the behavior. Therefore, the VLS D2-MSNs exhibited region-specific roles in nociception.

Mutual Influence of the Components of Human, Social and Psychological Capital: The Case of the Tyumen Region

On the basis of the database of a sociological survey conducted in 2020 in the Tyumen region (N = 1096), the authors consider interrelationships of the components of human, social and psychological capital components, which are measured using the objective characteristics of the respondents and their self-assessments. In order to classify the influence of various individual resources on the parameters of human, social and psychological capital, the authors build hierarchy trees models. Labor motivation is included into the number of factors of the three capital types. The consistency of the classical Minser model with self-assessments of human, social and psychological capital is verified. As the result, it is found that that the growth of self-assessments of human capital will reduce dramatically when people reach a median income. After median income is reached, the further growth depends on the length of service. If the income of people is much higher than the average, they will rate their social connections as more successful, while reward-oriented behavior reduces self-assessment of social capital. Using empirical data it is verified that following intrinsic motivation ensures the psychological well-being, in turn resulting in a corresponding increase in labor incomes.

Hyper BOLD Activation in Dorsal Raphe Nucleus of APP/PS1 Alzheimer\u2019s Disease Mouse during Reward-Oriented Drinking Test under Thirsty Conditions

Alzheimer’s disease (AD), a neurodegenerative disease, causes behavioural abnormalities such as disinhibition, impulsivity, and hyperphagia. Preclinical studies using AD model mice have investigated these phenotypes by measuring brain activity in awake, behaving mice. In this study, we monitored the behavioural alterations of impulsivity and hyperphagia in middle-aged AD model mice. As a behavioural readout, we trained the mice to accept a water-reward under thirsty conditions. To analyse brain activity, we developed a measure for licking behaviour combined with visualisation of whole brain activity using awake fMRI. In a water-reward learning task, the AD model mice showed significant hyperactivity of the dorsal raphe nucleus in thirsty conditions. In summary, we successfully visualised altered brain activity in AD model mice during reward-oriented behaviour for the first time using awake fMRI. This may help in understanding the causes of behavioural alterations in AD patients.

Dopaminergic influences on risk preferences of Parkinson’s disease patients

Clinicians are increasingly recognizing impulse control disorders (ICDs) as a complication of dopaminergic treatment in Parkinson's disease (PD). Considering the pivotal role of dopamine in reward information processing, ICDs may originate from dysregulation of reward-oriented behavior, and the behavioral changes may be reflected in shifts of psychological risk preference during decision-making. We used a behavioral economics paradigm to evaluate quantitatively the risk preferences of PD patients in levodopa on and off states. We also examined age-matched healthy controls. We found that levodopa increased the subjective value and prolonged the decision time in PD patients. These effects are apparently not explained by kinematic improvements but are attributed to psychological shifts of risk preferences and increased attention during risky decision-making. The risk preferences of healthy controls were similar to those of PD on levodopa treatment. The risk preferences of PD patients were not correlated with the scores of routine cognitive batteries, suggesting that dopamine-sensitive risk preferences are independent of cognitive capacities as measured by conventional batteries, including general intelligence, memory, and frontal functioning. By contrast, apathy and ICD partially predicted the risk attitude in PD patients, suggesting a common background of limbic origin behind these properties. The present results demonstrated that dopamine deficiency in off-state PD leads to risk-avoiding behavior and levodopa treatment increases the risk preferences. Behavioral economics framework is useful to evaluate short-term psychological changes in response to levodopa in PD patients.

Intact striatal dopaminergic modulation of reward learning and daily-life reward-oriented behavior in first-degree relatives of individuals with psychotic disorder.

Abnormalities in reward learning in psychotic disorders have been proposed to be linked to dysregulated subcortical dopaminergic (DA) neurotransmission, which in turn is a suspected mechanism for predisposition to psychosis. We therefore explored the striatal dopaminergic modulation of reward processing and its behavioral correlates in individuals at familial risk for psychosis. We performed a DA D2/3 receptor [18F]fallypride positron emission tomography scan during a probabilistic reinforcement learning task in 16 healthy first-degree relatives of patients with psychosis and 16 healthy volunteers, followed by a 6-day ecological momentary assessment study capturing reward-oriented behavior in the everyday life. We detected significant reward-induced DA release in bilateral caudate, putamen and ventral striatum of both groups, with no group differences in its magnitude nor spatial extent. In both groups alike, greater extent of reward-induced DA release in all regions of interest was associated with better performance in the task, as well as in greater tendency to be engaged in reward-oriented behavior in the daily life. These findings suggest intact striatal dopaminergic modulation of reinforcement learning and reward-oriented behavior in individuals with familial predisposition to psychosis. Furthermore, this study points towards a key link between striatal reward-related DA release and pursuit of ecologically relevant rewards.

P.3.b.007 - Intact striatal dopaminergic modulation of reward learning and daily-life reward-oriented behaviour in relatives of individuals with psychotic disorder

P.3.b.007 - Intact striatal dopaminergic modulation of reward learning and daily-life reward-oriented behaviour in relatives of individuals with psychotic disorder

Distinct Roles of Ventromedial versus Ventrolateral Striatal Medium Spiny Neurons in Reward-Oriented Behavior

The ventral striatum (VS) is a key brain center regulating reward-oriented behavior [1-4]. The VS can be anatomically divided into medial (VMS) and lateral (VLS) portions based on cortical input patterns. The VMS receives inputs from medial pallium-originated limbic structures (e.g., the medial prefrontal cortex [mPFC]), and the VLS receives inputs from the lateral pallium-originated areas (e.g., the insula) [5, 6]. This anatomical feature led us to hypothesize a functional segregation within the VS in terms of the regulation of reward-oriented behavior. Here, we engineered a fiber photometry system [4] and monitored population-level Ca2+ activities of dopamine D2-receptor-expressing medium spiny neurons (D2-MSNs), one of the major cell types in the striatum, during a food-seeking discrimination task. We found that VLS D2-MSNs were activated at the time of cue presentation. In stark contrast, VMS D2-MSNs were inhibited at this time point. Optogenetic counteraction of those changes in the VLS and VMS impaired action initiation and increased responding toward non-rewarded cues, respectively. During lever-press reversal training, VMS inhibition at the time of cue presentation temporarily ceased and optogenetic activation of VMS D2-MSNs facilitated acquisition of the new contingency. These data indicate that the opposing inhibition and excitation in VMS andVLS are important for selecting and initiating aproper action in a reward-oriented behavior. Wepropose distinct subregional roles within the VS in the execution of successful reward-oriented behavior.

Striatal dopaminergic modulation of reinforcement learning predicts reward—oriented behavior in daily life

Much human behavior is driven by rewards. Preclinical neurophysiological and clinical positron emission tomography (PET) studies have implicated striatal phasic dopamine (DA) release as a primary modulator of reward processing. However, the relationship between experimental reward-induced striatal DA release and responsiveness to naturalistic rewards, and therefore functional relevance of these findings, has been elusive.We therefore combined, for the first time, a DA D2/3 receptor [18F]fallypride PET during a probabilistic reinforcement learning (RL) task with a six day ecological momentary assessments (EMA) of reward-related behavior in the everyday life of 16 healthy volunteers. We detected significant reward-induced DA release in the bilateral putamen, caudate nucleus and ventral striatum, the extent of which was associated with better behavioral performance on the RL task across all regions. Furthermore, individual variability in the extent of reward-induced DA release in the right caudate nucleus and ventral striatum modulated the tendency to be actively engaged in a behavior if the active engagement was previously deemed enjoyable. This study suggests a link between striatal reward-related DA release and ecologically relevant reward-oriented behavior, suggesting an avenue for the inquiry into the DAergic basis of optimal and impaired motivational drive.

Mechanisms of the psychostimulant effects of caffeine: implications for substance use disorders.

The psychostimulant properties of caffeine are reviewed and compared with those of prototypical psychostimulants able to cause substance use disorders (SUD). Caffeine produces psychomotor-activating, reinforcing, and arousing effects, which depend on its ability to disinhibit the brake that endogenous adenosine imposes on the ascending dopamine and arousal systems. A model that considers the striatal adenosine A2A-dopamine D2 receptor heteromer as a key modulator of dopamine-dependent striatal functions (reward-oriented behavior and learning of stimulus-reward and reward-response associations) is introduced, which should explain most of the psychomotor and reinforcing effects of caffeine. The model can explain the caffeine-induced rotational behavior in rats with unilateral striatal dopamine denervation and the ability of caffeine to reverse the adipsic-aphagic syndrome in dopamine-deficient rodents. The model can also explain the weaker reinforcing effects and low abuse liability of caffeine, compared with prototypical psychostimulants. Finally, the model can explain the actual major societal dangers of caffeine: the ability of caffeine to potentiate the addictive and toxic effects of drugs of abuse, with the particularly alarming associations of caffeine (as adulterant) with cocaine, amphetamine derivatives, synthetic cathinones, and energy drinks with alcohol, and the higher sensitivity of children and adolescents to the psychostimulant effects of caffeine and its potential to increase vulnerability to SUD. The striatal A2A-D2 receptor heteromer constitutes an unequivocal main pharmacological target of caffeine and provides the main mechanisms by which caffeine potentiates the acute and long-term effects of prototypical psychostimulants.

Modulation of Premotor and Primary Motor Cortical Activity during Volitional Adjustments of Speed-Accuracy Trade-Offs.

Recent work suggests that while animals decide between reaching actions, neurons in dorsal premotor (PMd) and primary motor (M1) cortex reflect a dynamic competition between motor plans and determine when commitment to a choice is made. This competition is biased by at least two sources of information: the changing sensory evidence for one choice versus another, and an urgency signal that grows over time. Here, we test the hypothesis that the urgency signal adjusts the trade-off between speed and accuracy during both decision-making and movement execution. Two monkeys performed a reaching decision task in which sensory evidence continuously evolves over the course of each trial. In different blocks, task timing parameters encouraged monkeys to voluntarily adapt their behavior to be either hasty or conservative. Consistent with our hypothesis, during the deliberation process the baseline and gain of neural activity in decision-related PMd (29%) and M1 cells (45%) was higher when monkeys applied a hasty policy than when they behaved conservatively, but at the time of commitment the population activity was similar across blocks. Other cells (30% in PMd, 30% in M1) showed activity that increased or decreased with elapsing time until the moment of commitment. Movement-related neurons were also more active after longer decisions, as if they were influenced by the same urgency signal controlling the gain of decision-related activity. Together, these results suggest that the arm motor system receives an urgency/vigor signal that adjusts the speed-accuracy trade-off for decision-making and movement execution. Significance statement: This work addresses the neural mechanisms that control the speed-accuracy trade-off in both decisions and movements, in the kinds of dynamic situations that are typical of natural animal behavior. We found that many "decision-related" premotor and motor neurons are modulated in a time-dependent manner compatible with an "urgency" signal that changes between hasty and conservative decision policies. We also found that such modulation influenced cells related to the speed of the reaching movements executed by the animals to report their decisions. These results suggest that a unified mechanism determines speed-accuracy trade-off adjustments during decision-making and movement execution, potentially influencing both the cognitive and motor aspects of reward-oriented behavior.

Heterogeneity of the midbrain dopamine system: Implications for Parkinson disease.

The midbrain dopaminergic (DA) system is composed primarily of neurons in the substantia nigra pars compacta (SNc, area A10) and ventral tegmental area (VTA, area A9). These include at least 5 neuron subpopulations with distinct patterns of gene expression, electrophysiologic properties, projections to the striatum and cerebral cortex, and response to environmental stimuli. They are involved in several key brain functions, including action selection, motor performance, motivation and reward-based learning, working memory, and cognition. Midbrain DA neurons are activated by alerting signals involved in rapid detection of potentially relevant sensory cues. Most increase their activity in response to reward stimuli and are inhibited by aversive stimuli, thereby coding motivational value for learning reward-oriented behavior. Others are activated by aversive stimuli and code motivational salience of the stimulus. These different types of midbrain DA neurons are anatomically segregated and have specific afferent and efferent connections supporting specific aspects of behavior. Neurons encoding motivational value are located in the VTA and medial SNc and project primarily to the nucleus accumbens (NAc) and ventromedial prefrontal cortex and support Pavlovian learning of actions leading to successful outcomes. Neurons encoding motivational salience are located in the dorsolateral SNc and project to the dorsomedial striatum (primarily the caudate) and dorsolateral prefrontal cortex and modulate goal-oriented behavior. Neurons in the ventral tier of the SNc project to the dorsolateral striatum (putamen) and regulate habit formation and automatic motor behavior. Several features of ventral tier SNc neurons render them susceptible to oxidative stress and the subsequent neurodegeneration underlying Parkinson disease (PD). Involvement of other SNc and VTA neurons may contribute to nonmotor aspects of PD, such as depression, cognitive dysfunction, and impulse dyscontrol, in response to DA agonists. All these topics have been extensively discussed in several reviews.1–18

Septal Glucagon-Like Peptide 1 Receptor Expression Determines Suppression of Cocaine-Induced Behavior.

Glucagon-like peptide 1 (GLP-1) and its receptor GLP-1R are a key component of the satiety signaling system, and long-acting GLP-1 analogs have been approved for the treatment of type-2 diabetes mellitus. Previous reports demonstrate that GLP-1 regulates glucose homeostasis alongside the rewarding effects of food. Both palatable food and illicit drugs activate brain reward circuitries, and pharmacological studies suggest that central nervous system GLP-1 signaling holds potential for the treatment of addiction. However, the role of endogenous GLP-1 in the attenuation of reward-oriented behavior, and the essential domains of the mesolimbic system mediating these beneficial effects, are largely unknown. We hypothesized that the central regions of highest Glp-1r gene activity are essential in mediating responses to drugs of abuse. Here, we show that Glp-1r-deficient (Glp-1r(-/-)) mice have greatly augmented cocaine-induced locomotor responses and enhanced conditional place preference compared with wild-type (Glp-1r(+/+)) controls. Employing mRNA in situ hybridization we located peak Glp-1r mRNA expression in GABAergic neurons of the dorsal lateral septum, an anatomical site with a crucial function in reward perception. Whole-cell patch-clamp recordings of dorsal lateral septum neurons revealed that genetic Glp-1r ablation leads to increased excitability of these cells. Viral vector-mediated Glp-1r gene delivery to the dorsal lateral septum of Glp-1r(-/-) animals reduced cocaine-induced locomotion and conditional place preference to wild-type levels. This site-specific genetic complementation did not affect the anxiogenic phenotype observed in Glp-1r(-/-) controls. These data reveal a novel role of GLP-1R in dorsal lateral septum function driving behavioral responses to cocaine.

Personality traits and obesity: a systematic review

Based on a bio-social-ecological systems model of the development and maintenance of obesity, there has been in the last few years a growing research interest in the association of obesity and personality traits. The aim of the present review was a comprehensive and critical evaluation of the existing literature taking into account the methodological quality of studies to enhance our understanding of personality traits associated with body weight, the development of overweight and obesity as well as the effectiveness of weight loss interventions including bariatric surgery. Personality traits play an important role both as risk as well as protective factors in the development of overweight and obesity. While thus in particular 'neuroticism', 'impulsivity' and 'sensitivity to reward' appear as risk factors, 'conscientiousness' and 'self-control' have been shown to have a protective function in relation to weight gain. Conscientiousness is a measure of regulation of internal urges and self-discipline, and may thus provide a potential source of control over impulsive reward-oriented behaviour. The results of the present review suggest that, within the context of therapeutic weight reduction measures, it is meaningful to identify subgroups of patients for whom specific treatment options need to be developed, such as measures for strengthening self-control skills.

Persisting adiposity following chronic consumption of 10% sucrose solution: Strain differences and behavioural effects

The metabolic consequences of providing rats with extended access to sugar solutions have varied across studies. The two experiments in this study examined the effects of 8weeks of 24-h access to 10% sucrose solution on adult Wistar rats. This was followed by 6weeks of food restriction with no access to sucrose during which the behavioural effects of prior sucrose consumption on reward-oriented behaviour (Experiment 1) and reversal learning (Experiment 2) were assessed. In a comparison between rat strains, Experiment 1 found that sucrose accelerated weight gain in Albino but not Hooded Wistar rats, while sucrose-fed rats of both strains exhibited elevated fasting blood glucose and resistance to insulin. Importantly, at cull retroperitoneal fat deposits were elevated in sucrose-fed rats, at which point glucose and insulin had resolved to control levels and liver triglyceride content did not differ between groups. Experiment 2 also found that retroperitoneal fat content was higher in sucrose-fed rats at cull, after 6weeks of behavioural testing without sucrose and with restricted access to food, and found a similar effect for epididymal fat. Behavioural testing in Experiment 1 found that sucrose exposure had no effect on habit formation assessed using an outcome devaluation paradigm. However, instrumental responding by sucrose-fed Albino rats was the least affected by pre-feeding, indicating a relationship between sucrose-induced obesity and food-seeking behaviour. In Experiment 2, sucrose-fed and control rats did not differ on a discrimination reversal task. In conclusion, this study demonstrates that the behavioural and metabolic effects of sucrose consumption vary with strain. Further, results indicate that sucrose consumption can lead to lasting increases in adipose tissue stores, a finding which has significant implications for human diets.

Chronic restricted access to 10% sucrose solution in adolescent and young adult rats impairs spatial memory and alters sensitivity to outcome devaluation

Although increasing consumption of sugar drinks is recognized as a significant public health concern, little is known about (a) the cognitive effects resulting from sucrose consumption; and (b) whether the long-term effects of sucrose consumption are more pronounced for adolescents. This experiment directly compared performance on a task of spatial learning and memory (the Morris Water Maze) and sensitivity to outcome devaluation following 28days of 2-h/day access to a 10% sucrose solution in adolescent and young-adult Wistar rats. Sucrose groups developed elevated fasting blood glucose levels after the diet intervention, despite drawing <15% of calories from sucrose and gaining no more weight than controls. In subsequent behavioral testing, sucrose groups were impaired on the Morris Water Maze, with some residual deficits in spatial memory observed more than 6weeks after the end of sucrose exposure. Further, results from outcome devaluation testing indicated that in the older cohort of rats, those fed sucrose showed reduced sensitivity to devaluation of the outcome, suggestive of differences in instrumental learning following sucrose exposure. Data provide strong evidence that sucrose consumption can induce deficits in spatial cognition and reward-oriented behavior at levels that resemble patterns of sugar drink consumption in young people, and which can remain long after exposure.

Dopaminergic Control of Motivation and Reinforcement Learning: A Closed-Circuit Account for Reward-Oriented Behavior

Humans and animals take actions quickly when they expect that the actions lead to reward, reflecting their motivation. Injection of dopamine receptor antagonists into the striatum has been shown to slow such reward-seeking behavior, suggesting that dopamine is involved in the control of motivational processes. Meanwhile, neurophysiological studies have revealed that phasic response of dopamine neurons appears to represent reward prediction error, indicating that dopamine plays central roles in reinforcement learning. However, previous attempts to elucidate the mechanisms of these dopaminergic controls have not fully explained how the motivational and learning aspects are related and whether they can be understood by the way the activity of dopamine neurons itself is controlled by their upstream circuitries. To address this issue, we constructed a closed-circuit model of the corticobasal ganglia system based on recent findings regarding intracortical and corticostriatal circuit architectures. Simulations show that the model could reproduce the observed distinct motivational effects of D1- and D2-type dopamine receptor antagonists. Simultaneously, our model successfully explains the dopaminergic representation of reward prediction error as observed in behaving animals during learning tasks and could also explain distinct choice biases induced by optogenetic stimulation of the D1 and D2 receptor-expressing striatal neurons. These results indicate that the suggested roles of dopamine in motivational control and reinforcement learning can be understood in a unified manner through a notion that the indirect pathway of the basal ganglia represents the value of states/actions at a previous time point, an empirically driven key assumption of our model.

Differential Reward Coding in the Subdivisions of the Primate Caudate during an Oculomotor Task

The basal ganglia play a pivotal role in reward-oriented behavior. The striatum, an input channel of the basal ganglia, is composed of subdivisions that are topographically connected with different cortical and subcortical areas. To test whether reward information is differentially processed in the different parts of the striatum, we compared reward-related neuronal activity along the dorsolateral-ventromedial axis in the caudate nucleus of monkeys performing an asymmetrically rewarded oculomotor task. In a given block, a target in one position was associated with a large reward, whereas the other target was associated with a small reward. The target position-reward value contingency was switched between blocks. We found the following: (1) activity that reflected the block-wise reward contingency emerged before the appearance of a visual target, and it was more prevalent in the dorsal, rather than central and ventral, caudate; (2) activity that was positively related to the reward size of the current trial was evident, especially after reward delivery, and it was more prevalent in the ventral and central, rather than dorsal, caudate; and (3) activity that was modulated by the memory of the outcomes of the previous trials was evident in the dorsal and central caudate. This multiple reward information, together with the target-direction information, was represented primarily by individual caudate neurons, and the different reward information was represented in caudate subpopulations with distinct electrophysiological properties, e.g., baseline firing and spike width. These results suggest parallel processing of different reward information by the basal ganglia subdivisions defined by extrinsic connections and intrinsic properties.

Multiple Timescales of Memory in Lateral Habenula and Dopamine Neurons

Midbrain dopamine neurons are thought to signal predictions about future rewards based on the memory of past rewarding experience. Little is known about the source of their reward memory and the factors that control its timescale. Here we recorded from dopamine neurons, as well as one of their sources of input, the lateral habenula, while animals predicted upcoming rewards based on the past reward history. We found that lateral habenula and dopamine neurons accessed two distinct reward memories: a short-timescale memory expressed at the start of the task and a near-optimal long-timescale memory expressed when a future reward outcome was revealed. The short- and long-timescale memories were expressed in different forms of reward-oriented eye movements. Our data show that the habenula-dopamine pathway contains multiple timescales of memory and provide evidence for their role in motivated behavior.