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Considerable evidence suggests that rats can encode the relationship between actions and their specific consequences or outcomes and that this learning and its retrieval depend on dorsomedial striatum (DMS).To remain adaptive, however, such goal-directed learning needs to remain flexible;animals need to remain sensitive to changes in the consequences that an action might produce and yet changes of this kind produce a significant problem: new learning has to be shielded from interference produced by old learning if it is to be accurately retrieved.There is some evidence that cholinergic activity in both the hippocampus and the cortex, although relevant to different functions, protects new learning from interference of this kind and, so we sought to assess whether cholinergic activity played this role in striatum.The main source of acetylcholine in the striatum is a class of tonically active, giant, aspiny interneurons known collectively as cholinergic interneurons (CIN).We produced a deficit in their main input from parafascicular thalamus (Pf) and found that (i) both their metabolic activity and firing rate were strongly attenuated and, more importantly, (ii) changing the action-outcome contingency resulted in an inability to retrieve both new and old action-outcome associations.Disconnection of the Pf from DMS produced a similar behavioural effect as did intra-DMS infusion of the M2 agonist oxotremorine, which acts to inhibit CIN firing and acetylcholine release.These data support the hypothesis that CINs are necessary to protect goal-directed learning in striatum from catastrophic interference.Further evidence for this claim has come from an assessment of specific changes in CINs induced by selective ablation techniques as well as changes in CIN activity that accompany normal aging and this evidence will also be discussed.