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内容記述 |
Primates must adapt to changing environments by optimizing their behavior to make beneficial choices. At the core of adaptive behavior is the orbitofrontal cortex (OFC), specifically Brodmann's area 11/13, of the brain, which updates choice value through direct experience or knowledge-based inference. Subcortical structures, such as the rostromedial part of the caudate nucleus (rmCD) and the medial part of the mediodorsal thalamus (MDm), receive direct projections from the OFC, and are thought to be also involved in such adaptive behavior. However, the causal contributions of these areas and neural pathways connecting them to these different value-updating strategies remain unidentified in primates. In this study, we used a chemogenetic tool, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), to reversibly silence the activity of the OFC and to suppress synaptic transmission from the OFC to two subcortical areas. We designed two behavioral tasks in which two male macaque monkeys updated the values of certain items, either by directly experiencing changes in stimulus-reward associations, or by inferring the value of unexperienced items based on the task’s rules. Chemogenetic silencing of bilateral OFC through systemic injection of agonists, deschloroclozapine, combined with the analysis fitting the data with reinforcement learning models revealed that monkey OFC is causally involved in updating item value based on both experience and inference. In vivo imaging of chemogenetic receptors by positron emission tomography allowed us to map projections from the OFC to the rmCD and MDm. Chemogenetic silencing of the OFC-rmCD pathway through local infusion of agonists at axonal terminals impaired experience-based value updating, while silencing the OFC-MDm pathway impaired inference-based value updating. Our results thus demonstrate dissociable contributions of distinct OFC-subcortical projections to different behavioral strategies, and provide new insights into the neural basis of value-based adaptive decision-making in primates. |
