Adaptive reward-related decision making requires accurate prospective consideration of the specific outcome of each option and its current desirability. Often this information must be inferred based on the presence of predictive environmental events. The basolateral amygdala (BLA) and medial orbitofrontal cortex (mOFC) are two key nodes in the circuitry supporting such outcome expectations, but very little is known about the function of direct connections between these regions. Here, in male rats, we first anatomically confirmed the existence of bidirectional, direct projections between the mOFC and BLA and found that BLA projections to mOFC are largely distinct from those to lateral OFC (lOFC). Next, using pathway-specific chemogenetic inhibition and the outcome-selective Pavlovian-to-instrumental transfer and devaluation tests, we interrogated the function of the bidirectional mOFC–BLA connections in reward-directed behavior. We found evidence that the mOFC->BLA pathway mediates the use of environmental cues to understand which specific reward is predicted, information needed to infer which action to choose, and how desirable that reward is to ensure adaptive responses to the cue. By contrast, the BLA->mOFC pathway is not needed to use the identity of an expected reward to guide choice but does mediate adaptive responses to cues based on the current desirability of the reward they predict. These functions differ from those we previously identified for the lOFC–BLA circuit. Collectively, the data reveal the mOFC–BLA circuit as critical for the cue-dependent reward outcome expectations that influence adaptive behavior and decision making.

SIGNIFICANCE STATEMENT To make good decisions we evaluate how advantageous a particular course of action would be. This requires understanding what rewarding outcomes can be expected and how desirable they currently are. Such prospective considerations are critical for adaptive decision making but disrupted in many psychiatric diseases. Here, we reveal that direct connections between the medial orbitofrontal cortex and basolateral amygdala mediate these functions. These findings are especially important in light of evidence of dysfunction in this circuit in substance use disorder and mental illnesses marked by poor decision making.

与奖励相关的自适应决策需要对每个选项的具体结果及其当前的可取性进行准确的前瞻性考虑。通常必须根据预测性环境事件的存在来推断此信息。基底外侧杏仁核 (BLA) 和内侧眶额皮质 (mOFC) 是支持这种结果预期的电路中的两个关键节点，但对这些区域之间直接连接的功能知之甚少。在这里，在雄性大鼠中，我们首先在解剖学上证实了 mOFC 和 BLA 之间存在双向、直接投射，并发现 BLA 对 mOFC 的投射与侧向 OFC (lOFC) 的投射在很大程度上不同。接下来，使用通路特异性化学遗传学抑制和结果选择性巴甫洛夫到仪器的转移和贬值测试，我们询问了双向 mOFC-BLA 连接在奖励导向行为中的功能。我们发现证据表明，mOFC->BLA 通路介导环境线索的使用，以了解预测的特定奖励、推断选择哪种行动所需的信息，以及该奖励对于确保对线索的适应性反应的可取性。相比之下，BLA->mOFC 通路不需要使用预期奖励的同一性来指导选择，而是根据他们预测的奖励的当前可取性来调节对线索的适应性反应。这些功能不同于我们之前为 lOFC-BLA 电路确定的功能。总的来说，数据显示 mOFC-BLA 电路对于影响适应性行为和决策的依赖于线索的奖励结果期望至关重要。

意义声明为了做出正确的决定，我们会评估特定行动方案的优势程度。这需要了解可以预期哪些有益的结果以及它们目前的可取性。这种前瞻性考虑对于适应性决策至关重要，但在许多精神疾病中被破坏。在这里，我们揭示了内侧眶额皮质和基底外侧杏仁核之间的直接联系介导了这些功能。鉴于物质使用障碍和以决策失误为特征的精神疾病中该回路功能障碍的证据，这些发现尤其重要。