For this test rats received four reinstatement trials before each of which a single outcome was delivered. After each outcome, delivery responding during the next 2 min was recorded (i.e., the postoutcome period) recorded (Figure 3A). Performance in the final 2 min of extinction and prior to each of the reinstatement trials served as the pretest period. As is clear from Figure 3I, the Sham group reinstated performance of the action most recently associated with the delivered outcome (i.e., Post-reinst) relative to

the other action (Post-other). In contrast, both actions were reinstated in the Pf-lesioned Selleck Dorsomorphin group in an undifferentiated manner. Accordingly, although there was no effect of group, F (1, selleck products 10) = 0.8, p = 0.392, responding on the reinstated action relative to the other action differed between groups; in the sham group, the increase in responding was specific to the reinstated lever, F (1, 10) = 11.68, p = 0.007, whereas

in the Pf group, it was not and was similarly distributed between the two levers, F (1, 10) = 0.99, p = 0.343. Together, the contingency degradation, devaluation, and outcome-specific reinstatement tests confirm that Pf-lesioned rats were unable to use action-outcome information to guide instrumental performance after the initial contingencies were altered. Although our initial results imply that the effects of Pf lesions on action-outcome encoding and retrieval were secondary to their effects on cholinergic activity in striatum, we sought to confirm

this more directly in two further experiments in which we disconnected the Pf from the pDMS using (1) asymmetrical lesions and (2) pharmacological blockade of cholinergic activity. The logic behind disconnection experiments is straightforward (Everitt et al., 1991): if the Pf and pDMS are functionally connected, then, for example, combining a unilateral Pf lesion with a unilateral lesion of the pDMS in the contralateral hemisphere should disconnect these structures and disrupt this function. Hence, for this experiment, we compared a group that received contralateral (Contra) Pf and pDMS lesions with a group that received ipsilateral (Ipsi) lesions during of these structures, inducing the same degree of cell loss while preserving the Pf-DMS pathway in the one hemisphere. To evaluate any impairment in the Ipsi group, a Sham control was also included. Representative lesions are shown in Figure 4A and schematically in Figure 4I. After recovery from surgery, we conducted a direct replication of the behavioral procedures previously described, the results of which are presented in Figure 4. As is clear from this figure, the effect of the disconnection was similar to that induced by bilateral Pf lesions.