Genetic and Circuit Mechanisms Underlying Natural Variation in Value-Based Decision Making

How natural regulatory genetic variation shapes innate economic decision biases by modifying neural circuit structure and function remains poorly understood. Here, we trace this pathway using a value-based oviposition decision in Drosophila. While laboratory flies reject sucrose in favor of a plain substrate, a wild-caught African strain accepts sucrose. This behavioral divergence maps to three African-specific intronic SNPs in the gene pumilio (pum), encoding an RNA-binding translational repressor. These SNPs downregulate pum, derepressing its target - the voltage-gated sodium channel paralytic (para) - in a pair of GABAergic interneurons that encode option values. Increased para enhances excitability, compresses neuronal value-coding differences between sucrose and plain options, and promotes sucrose acceptance. Selectively reducing pum or overexpressing para in these neurons converts laboratory flies to the African phenotype at physiological and behavioral levels. Our findings provide a genome-to-circuit-to-behavior model, illustrating how subtle regulatory polymorphisms reshape neural computations to drive adaptive variation in economic decision-making.