Orbitofrontal inactivation impairs reversal of Pavlovian learning by interfering with 'disinhibition' of responding for previously unrewarded cues.

Orbitofrontal cortex (OFC) is critical for reversal learning. Reversal deficits are typically demonstrated in complex settings that combine Pavlovian and instrumental learning. Yet recent work has implicated the OFC specifically in behaviors guided by cues and the features of the specific outcomes they predict. To test whether the OFC is important for reversing such Pavlovian associations in the absence of confounding instrumental requirements, we trained rats on a simple Pavlovian task in which two auditory cues were presented, one paired with a food pellet reward and the other presented without reward. After learning, we reversed the cue-outcome associations. For half the rats, OFC was inactivated prior to each reversal session. Inactivation of OFC impaired the ability of the rats to reverse conditioned responding. This deficit reflected the inability of inactivated rats to develop normal responding for the previously unrewarded cue; inactivation of OFC had no impact on the ability of the rats to inhibit responding to the previously rewarded cue. These data show that OFC is critical to reversal of Pavlovian responding, and that the role of OFC in this behavior cannot be explained as a simple deficit in response inhibition. Furthermore, the contrast between the normal inhibition of responding, reported here, and impaired inhibition of responding during Pavlovian over-expectation, reported previously, suggests the novel hypothesis that OFC may be particularly critical for learning (or behavior) when it requires the subject to generate predictions about outcomes by bringing together or integrating disparate pieces of associative information.