δ-Opioid and dopaminergic processes in accumbens shell modulate the cholinergic control of predictive learning and choice

Decision-making depends on the ability to extract predictive information from the environment to guide future actions. Outcome-specific Pavlovian-instrumental transfer (PIT) provides an animal model of this process in which a stimulus predicting a particular outcome biases choice toward actions earning that outcome. Recent evidence suggests that cellular adaptations of δ-opioid receptors (DORs) on cholinergic interneurons (CINs) in the nucleus accumbens shell (NAc-S) are necessary for PIT. Here we found that modulation of DORs in CINs critically influences D1-receptor (D1R)-expressing projection neurons in the NAc-S to promote PIT. First, we assessed PIT-induced changes in signaling processes in dopamine D1- and D2-receptor-expressing neurons using drd2-eGFP mice, and found that PIT-related signaling was restricted to non-D2R-eGFP-expressing neurons, suggesting major involvement of D1R-neurons. Next we confirmed the role of D1Rs pharmacologically: the D1R antagonist SCH-23390, but not the D2R antagonist raclopride, infused into the NAc-S abolished PIT in rats, an effect that depended on DOR activity. Moreover, asymmetrical infusion of SCH-23390 and the DOR antagonist naltrindole into the NAc-S also abolished PIT. DOR agonists were found to sensitize the firing responses of CINs in brain slices prepared immediately after the PIT test. We confirmed the opioid-acetylcholinergic influence over D1R-neurons by selectively blocking muscarinic M4 receptors in the NAc-S, which tightly regulate the activity of D1Rs, a treatment that rescued the deficit in PIT induced by naltrindole. We describe a model of NAc-S function in which DORs modulate CINs to influence both D1R-neurons and stimulus-guided choice between goal-directed actions

Striatal dopamine release tracks the relationship between actions and their consequences

Summary: The acquisition and performance of goal-directed actions has long been argued to depend on the integration of glutamatergic inputs to the posterior dorsomedial striatum (pDMS) under the modulatory influence of dopamine. Nevertheless, relatively little is known about the dynamics of striatal dopamine during goal-directed actions. To investigate this, we chronically recorded dopamine release in the pDMS as rats acquired two actions for distinct outcomes as these action-outcome associations were incremented and then subsequently degraded or reversed. We found that bilateral dopamine release scaled with action value, whereas the lateralized dopamine signal, i.e., the difference in dopamine release ipsilaterally and contralaterally to the direction of the goal-directed action, reflected the strength of the action-outcome association independently of changes in movement. Our results establish, therefore, that striatal dopamine activity during goal-directed action reflects both bilateral moment-to-moment changes in action value and the long-term action-outcome association

Resolution of conflict between goal-directed actions: outcome encoding and neural control processes

According to O-R theory of instrumental learning, incongruent biconditional discriminations should be impossible to solve in a goal-directed manner because the event acting as the outcome of one response also acts as a discriminative stimulus for an opposite response. Each event should therefore be associated with two competing responses. However, Dickinson and de Wit (2003) have presented evidence that rats can learn incongruent discriminations. The present study investigated whether rats were able to engage additional processes to solve incongruent discriminations in a goal-directed manner. Experiment 1 provides evidence that rats resolve the response conflict that arises in the incongruent discrimination by differentially encoding events in their roles as discriminative stimulus and as outcome. Furthermore, Experiment 2 shows that once goal-directed control has been established the dorsomedial prefrontal cortex is not directly involved in its maintenance but rather plays a central role in conflict resolution processes

Intact corticostriatal control of goal-directed action in Alcohol Use Disorder: a Pavlovian-to-instrumental transfer and outcome-devaluation study

Deficits in instrumental, goal-directed control, combined with the influence of drug-associated Pavlovian-conditioned stimuli, are thought to influence the development and maintenance of addiction. However, direct evidence has mainly come from animal studies. We sought to establish whether alcohol use disorder (AUD) is characterized by behavioral or neurobiological deficits in (i) the integration of Pavlovian and instrumental values and (ii) goal-directed control; and (iii) whether duration or severity of AUD is associated with such deficits. The influence of cues predicting food rewards on instrumental action was assessed in a Pavlovian-to-instrumental transfer (PIT) test, measuring both specific and general PIT, and goal-directed behavior in an outcome-devaluation test. Brain activity was measured using functional MRI in 38 abstinent individuals with AUD and 22 matched healthy control individuals (HCs). We found significant specific and general PIT and outcome-devaluation effects across groups indicating goal-directed control, mediated by distinct corticostriatal signals, but no significant differences between individuals with AUD and healthy controls. Bayesian analyses provided substantial-to-strong evidence for the absence of group differences for these effects, or any relationship with duration or severity of AUD. These results suggest intact ability to integrate action-outcome associations on specific and general PIT and goal-directed learning in AUD during abstinence