The capacity for goal-directed action depends on encoding specific action-outcome associations, a learning process mediated by the posterior dorsomedial striatum (pDMS). In a changing environment, plasticity has to remain flexible, requiring interference between new and existing learning to be minimized, yet it is not known how new and existing learning are interlaced in this way. Here we investigated the role of the thalamostriatal pathway linking the parafascicular thalamus (Pf) with cholinergic interneurons (CINs) in the pDMS in this process. Removing the excitatory input from Pf to the CINs was found to reduce the firing rate and intrinsic activity of these neurons and produced an enduring deficit in goal-directed learning after changes in the action-outcome contingency. Disconnection of the Pf-pDMS pathway produced similar behavioral effects. These data suggest that CINs reduce interference between new and existing learning, consistent with claims that the thalamostriatal pathway exerts state control over learning-related plasticity.