Project Summary The explore-exploit dilemma refers to the challenge of deciding when to forego choices with known consequences to explore new opportunities and learn more about them. Managing this trade-off is a fundamental component of behavioral flexibility. Excessive exploration or exploitation impedes learning and results in poor choices leading to undesired outcomes. Explore-exploit decision making is understudied in psychiatry despite its ecological validity and relevance in understanding disorders characterized by inflexible behaviors. One reason for this is we have not identified if the brain encodes information relevant for managing explore-exploit tradeoffs differently when exploration is motivated by either appetitive or aversive consequences. Another reason is that while there is evidence in humans that frontopolar cortex—the most anterior part of prefrontal cortex which is unique to primates—implements decisions to explore new opportunities, the neural mechanisms underlying changes in frontopolar activity that prompt exploration are unclear. Neurons in the orbitofrontal cortex, basolateral amygdala, and nucleus accumbens encode value signals that inform explore-exploit decisions. This suggests a more dynamic interplay between frontopolar cortex and motivational brain regions during explore- exploit decision making than is currently hypothesized. This proposal tests the hypothesis that frontopolar cortex implements decisions to explore, but is reliant on appetitive and aversive value signals computed in motivational neural circuits to balance exploration and exploitation. We predict that bottom-up feedback to frontopolar cortex from brain regions classically associated with signaling reward value is critical for balancing exploration and exploitation. In Aim 1 we will test if monkeys explore more often when choices in a multi-arm bandit task are associated with gains or losses, and use computational modeling of choices to define valence dependent differences in their willingness to explore. In Aim 2 we will simultaneously record neural activity in frontopolar and orbitofrontal cortex, basolateral amygdala, and nucleus accumbens to determine if bottom-up information flow from motivational brain regions to frontopolar cortex predicts decisions to explore or exploit, and if exploratory choices are encoded differently when exploration is motivated by gains versus losses. In Aim 3 will use pathway-specific chemogenetics to excite or inhibit basolateral amygdala neurons that project to the nucleus accumbens, while recording neural activity in the nucleus accumbens and frontopolar cortex. We will to test the prediction that excitation of this pathway increases exploitation due to heightened encoding of exploitative signals in nucleus accumbens and decreased encoding of exploration signals in frontopolar cortex. Upon completion of these aims, we will understand how imbalances in explore-exploit decision making emerge in different psychiatric ...