Medial Orbitofrontal, Prefrontal, and Amygdalar Circuits Support Dissociable Component Processes of Risk/Reward Decision-Making

The medial orbitofrontal cortex (mOFC) has been implicated in shaping decisions involving reward uncertainty, in part by using memories to infer future outcomes. This region is interconnected with other key systems that mediated these decisions, including the basolateral amygdala (BLA) and prelimbic (PL) region of the medial prefrontal cortex, yet the functional importance of these circuits remains unclear. The present study used chemogenetic silencing to examine the contribution of different input and output pathways of the mOFC to risk/reward decision making. Male rats were well-trained on a probabilistic discounting task where they chose between a small/certain (1 pellet) and a large/uncertain 4 pellet option, the odds for which changed systematically across a session. Suppressing activity of descending mOFC terminals in the BLA impaired adjustment in choice biases as reward probabilities change, suggesting this circuit tracks changes in relative value to support flexible reward-seeking. Inhibiting bottom-up BLA→mOFC circuits had no effect on choice. With respect to cortico-cortical circuits, inhibiting mOFC inputs to PL led to more random choice patterns, indicating this circuit promotes advantageous choice by processing context-dependent information regarding wins and losses. In comparison, PL inputs to mOFC attenuates the allure of larger yet uncertain rewards and reduces loss sensitivity, particularly early in the choice sequence. The present findings provide novel insight into the functional contribution that mOFC/BLA and PL interactions make to distinct processes that shape decision making in situations of reward uncertainty.<b>Significance Statement</b> The medial orbitofrontal cortex supports the use of reward memories to guide efficient value-based decision-making, yet the functional circuits through which it mediates this form of cognition is unclear. The present study revealed that different mOFC interactions with the BLA and the PL facilitate dissociable component processes of decisions involving risks and rewards. These findings clarify the functions of cortico-cortical and cortico-amygdalar pathways and may have implications for understanding how dysfunction in these circuits relates to aberrant decision making seen in certain psychiatric disorders.