Orbitofrontal circuits for context-gated reward predictions

The orbitofrontal cortex (OFC) is essential for the contextual regulation of reward predictions, yet the circuit mechanisms underlying this function remain unclear. Here, we dissected the roles of two major OFC efferent pathways --projections to the central dorsal striatum (CDS) and the mediodorsal thalamus (MDT)-- in contextual regulation. Male and female rats performed a context-dependent discrimination task in which the reward-predictive status of two auditory target cues (X and Y) was determined by a visual contextual cue (A). Using temporally precise optogenetic inhibition of OFC terminals, we found that silencing OFC[->]CDS profoundly disrupted contextual gating, virtually abolishing the negatively gated component (A:Y- / Y+) while producing modest effects on the positively gated component (A:X+ / X-). In contrast, OFC[->]MDT inhibition produced modest and qualitatively distinct effects, characterized by a generalized increase in responding in context A and a decrease in context noA. These effects were reproduced in a connectionist model in which context influenced predictions either additively (via elemental representations) or by acting as a gatekeeper (via configural cue/context representations). Disrupting the configural pathway mimicked OFC[->]CDS silencing, whereas amplifying additive contextual inputs replicated OFC[->]MDT inhibition. Together, these findings reveal complementary circuit mechanisms through which the OFC shapes context-appropriate reward seeking.