Partially dissociable roles of the Orbitofrontal cortex and dorsal Hippocampus in context-dependent (hierarchical) reward prediction and contextual inference in learning

Reward cues are often ambiguous; what is good in one context is not necessarily good in another context. To solve this ambiguity, animals form hierarchical associations in which the context acts as a gatekeeper in the retrieval of the appropriate cue-evoked memory, ensuring context-appropriate behavior. These hierarchical associative structures also influence future learning by promoting the formation of new context-dependent associations (leading to the inference of context-dependency for new associations). The orbitofrontal cortex (OFC) and the dorsal hippocampus (DH) are both proposed to encode a “cognitive map” that includes the representation of hierarchical, context-dependent, associations. However the causal role of the OFC and DH in the different functional properties of hierarchical associations remains controversial. Here we used chemogenetic inactivations, in rats, to examine the role of OFC and DH in 1) the contextual regulation of performance, and 2) the contextual learning bias conferred by hierarchical associations. We show that OFC is required for both manifestations of hierarchical associations. In contrast, DH contribution appears limited to the contextual learning bias. This study provides novel insight into the different functional properties of context-dependent hierarchical associations, and establishes the OFC as a critical orchestrator of these different contextual effects.