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

Genetically encoded differences in value-related functions are believed to influence decision biases in animals, yet direct causal evidence remains scarce. Here, we demonstrate how naturally occurring genetic variation between two Drosophila strains leads to distinct choices in an egg-laying-based decision-making task, where both sucrose and plain substrates are viable options. We identify a pair of long-range GABAergic neurons, Earmuff, that lower an option’s intrinsic value and are both necessary and sufficient for shaping the flies’ preferences. Further analysis reveals that expression-modifying single nucleotide polymorphisms (SNPs) within introns of the gene encoding the RNA-binding molecule pumilio ( pum ) – a known negative regulator of the voltage-gated sodium channel NaV ⁺ – exist between the two strains. These SNPs drive variation in pum expression within Earmuff, altering how each strain values the two substrates and biasing its decisions. Our findings establish a mechanistic link between genetic variation and the neural circuitry that governs value-based decision-making.