ABSTRACTAdaptive reward-related decision making requires accurate prospective consideration of the current availability and desirability of potential rewarding options. 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 guided behavior, 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 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 predict which reward is available, information needed to infer which action to choose, and how desirable that reward is to ensure adaptive cue responses. By contrast, the BLA→mOFC pathway is not needed to use cues to know which reward is available but is needed to use the current desirability of that reward to infer how advantageous it would be to respond to the cue. These functions differ from those we previously identified for the lOFC-BLA circuit. Collectively, these data reveal the mOFC-BLA circuit as critical for the cue-dependent reward outcome expectations that influence adaptive behavior and decision making.SIGNIFICANCE STATEMENTTo make good decisions we evaluate how advantageous a particular course of action would be. This requires understanding what rewarding events might be available and how desirable those events are currently. Such prospective considerations are critical for adaptive decision making but are 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.
Long-Term Effects of Chronic Buspirone during Adolescence Reduce the Adverse Influences of Neonatal Inflammatory Pain and Stress on Adaptive Behavior in Adult Male Rats
