Differential effects of inactivation of the orbitofrontal cortex on strategy set-shifting and reversal learning.

Different subregions of the rodent prefrontal cortex (PFC) mediate dissociable types of behavioral flexibility. For example, lesions of the medial or orbitofrontal (OFC) regions of the PFC impair extradimensional shifts and reversal learning, respectively, when novel stimuli are used during different phases of the task. In the present study, we assessed the effects of inactivation of the OFC on strategy set-shifting and reversal learning, using a maze based set-shifting task mediated by the medial PFC. Long-Evans rats were trained initially on a visual-cue discrimination to obtain food. On the subsequent day, rats had to shift to using a response strategy (e.g., always turn left). On Day 3 (reversal), rats were required to reverse the direction of their turn (e.g., always turn right). Infusions of the local anesthetic bupivacaine into the OFC did not impair initial visual discrimination learning, nor did it impair performance on the set-shift. In contrast, inactivation of the OFC did impair reversal learning; yet, these rats ceased using the previously acquired response rule as readily as controls. Instead, rats receiving OFC inactivations made a disproportionate number of erroneous arm entries towards the visual-cue, suggested that these animals reverted back to using the original visual-cue based strategy. These findings, in addition to previous data, further support the notion that the OFC and medial PFC play dissociable roles in reversal learning and set-shifting. Furthermore, the lack of effect of OFC inactivations on the set-shift indicates that this type of behavioral flexibility does not require cognitive operations related to reversal learning.