ReviewToward a theoretical role for tonic norepinephrine in the orbitofrontal cortex in facilitating flexible learning

- Model-based reinforcement learning depends on assigning new learning to the appropriate 'state'.
- Orbitofrontal cortex represents task states during and after learning, akin to model-based RL states.
- Tonic norepinephrine tracks environmental changes, driving behavior shifts during task changes.
- Specific noradrenergic projections to OFC may drive remapping of OFC cue-outcome associations.

To adaptively respond in a complex, changing world, animals need to flexibly update their understanding of the world when their expectations are violated. Though several brain regions in rodents and primates have been implicated in aspects of this updating, current models of orbitofrontal cortex (OFC) and norepinephrine neurons of the locus coeruleus (LC-NE) suggest that each plays a role in responding to environmental change, where the OFC allows updating of prior learning to occur without overwriting or unlearning one's previous understanding of the world that changed, while elevated tonic NE allows for increased flexibility in behavior that tracks an animal's uncertainty. In light of recent studies highlighting a specific LC-NE projection to the OFC, in this review we discuss current models of OFC and NE function, and their potential synergy in the updating of associations following environmental change.