Partially dissociable roles of the orbitofrontal cortex and dorsal hippocampus in context-dependent hierarchical associations

Reward cues are often ambiguous; what is good in one context is not necessarily good in another. To solve this ambiguity, animals form hierarchical associations in which the context gates the retrieval of appropriate cue-evoked memories. These hierarchical associations regulate cue-elicited behavior and influence subsequent learning, promoting the inference of context-dependency. The orbitofrontal cortex (OFC) and dorsal hippocampus (DH) are both proposed to encode a "cognitive map" encompassing hierarchical, context-dependent associations. However, OFC- and DH-specific contributions to the different functional properties of hierarchical associations remain controversial. Using chemogenetic inactivation in rats, we show that the OFC is essential to both properties of hierarchical associations (performance regulation and learning bias). In contrast, DH's role appears limited to the contextual learning bias conferred by hierarchical associations. This work establishes the OFC as a critical orchestrator of hierarchical associations and provides insights into the extended circuits mediating the functional properties of these associations.Reward cues are often ambiguous; what is good in one context is not necessarily good in another. To solve this ambiguity, animals form hierarchical associations in which the context gates the retrieval of appropriate cue-evoked memories. These hierarchical associations regulate cue-elicited behavior and influence subsequent learning, promoting the inference of context-dependency. The orbitofrontal cortex (OFC) and dorsal hippocampus (DH) are both proposed to encode a "cognitive map" encompassing hierarchical, context-dependent associations. However, OFC- and DH-specific contributions to the different functional properties of hierarchical associations remain controversial. Using chemogenetic inactivation in rats, we show that the OFC is essential to both properties of hierarchical associations (performance regulation and learning bias). In contrast, DH's role appears limited to the contextual learning bias conferred by hierarchical associations. This work establishes the OFC as a critical orchestrator of hierarchical associations and provides insights into the extended circuits mediating the functional properties of these associations.