A cortical-basal ganglia network involving, particularly, the posterior region of dorsomedial striatum (DMS) has been implicated in the acquisition of goal-directed actions; however, no direct evidence of learning-related plasticity in this striatal region has been reported, nor is it known whether, or which, specific cell types are involved in this learning process. The striatum is primarily composed of two classes of spiny projection neurons (SPNs): the striatonigral and striatopallidal SPNs, which express dopamine D1 and D2 receptors, respectively. Here we establish that, in mice, the acquisition of goal-directed actions induced plasticity in both D1-and D2-SPNs specifically in the DMS and, importantly, that these changes were in opposing directions; after learning, AMPA/NMDA ratios were increased in D1-SPNs and reduced in the D2-SPNs in the DMS. Such opposing plasticity could provide the basis for rapidly rebiasing the control of task-specific actions, and its dysregulation could underlie disorders associated with striatal function.

We review recent studies assessing the role of the bed nucleus of the stria terminalis (BNST) in the motivational control of instrumental conditioning. This evidence suggests that the BNST and central nucleus of the amygdala (CeA) form a circuit that modulates the ventral tegmental area (VTA) input to the nucleus accumbens core (NAc core) to control the influence of Pavlovian cues on instrumental performance. In support of these claims, we found that activity in the oval region of BNST was increased by instrumental conditioning, as indexed by phosphorylated ERK activity (Experiment 1), but that this increase was not due to exposure to the instrumental contingency or to the instrumental outcome per se (Experiment 2). Instead, BNST activity was most significantly incremented in a test conducted when the instrumental outcome was anticipated but not delivered, suggesting a role for BNST in the motivational effects of anticipated outcomes on instrumental performance. To test this claim, we examined the effect of NMDA-induced cell body lesions of the BNST on general Pavlovian-to-instrumental transfer (Experiment 3). These lesions had no effect on instrumental performance or on conditioned responding during Pavlovian conditioning to either an excitory conditioned stimulus (CS) or a neutral CS (CS0) but significantly attenuated the excitatory effect of the Pavlovian CS on instrumental performance. These data are consistent with the claim that the BNST mediates the general excitatory influence of Pavlovian cues on instrumental performance and suggest BNST activity may be central to CeA-BNST modulation of a VTA-NAc core circuit in incentive motivation.