However, in neither the devaluation nor the reinstatement tests was this indifference due merely to a failure to choose; the overall rate of choice performance summed across both actions during these tests was generally similar to the controls, particularly

in MLN0128 mouse the reinstatement tests. It is also important to note that the effect of the change in contingency was not due to an interaction with the pretraining treatment; posttraining inactivation of the CINs using oxotremorine had a similar effect when introduced only during new learning after the initial training phase was complete. Indeed, this similarity in the effects of the lesion- and oxotremorine-induced disconnection suggests that the source of the effects of both treatments was probably similar. In addition to their expression on CINs, however, M2 receptors are also expressed on cortical terminals (Ding et al., 2010; Goldberg et al., 2012) and so, in addition to inhibiting acetycholine release at the CINs, oxotremorine can also suppress glutamate release and ongoing motor behavior (Hersch et al., 1994). Nevertheless, although oxotremorine differed from the Pf lesion by mildly suppressing

instrumental performance during training, the overall similarity in the effects of these treatments both behaviorally and on CIN function suggests that it was the LBH589 latter influence of the drug, rather than its effect on cortical terminals, that was functionally the more critical in the current study. The current results suggest that the thalamostriatal pathway contributes to Rebamipide new goal-directed learning through its projections specifically to the posterior, and not the anterior, DMS during instrumental conditioning. We found that this pathway largely governs CIN activity, as demonstrated by clear changes in activity in, and the pharmacological correlates of, the disconnection procedure. Nevertheless, it is important to recognize: (1) that the effects of Pf manipulation could be mediated by indirect thalamostriatal

connections and, more critically, (2) that any effects of altered CIN function can only be manifest through changes in projection MSN activity, in this case, changes in the segregation of plasticity at the MSNs after new learning. Indeed, in animals perfused right after expressing goal-directed behaviors, we found evidence of enhanced neuronal responses in MSNs when the Pf projections had been interrupted. These results cannot be explained by a loss in the direct drive of canonical glutamatergic inputs onto MSNs, as Pf denervation would reduce, rather than increase, activity on these neurons. Instead, our observations support more recent views of how the Pf inputs modulate striatal function. In a recent study, Ellender et al.