Pain is so close to pleasure: the same dopamine neurons can mediate approach and avoidance in Drosophila

Abstract

Dopaminergic neurons (DANs) have long been implicated in reward, punishment, and value processing across animal phyla, yet whether individual DAN subpopulations convey generalized valence signals or serve more specialized functions remains contested. We addressed this question directly by screening about fifty Drosophila DAN subpopulations for their ability to drive consistent approach or avoidance across different operant behavioral paradigms in which flies controlled contingent optogenetic DAN activation through their own behavior. No single DAN subpopulation drove consistent preferences across all paradigms, and DAN activation produced substantially weaker valence effects than activation of sensory neurons used as positive controls. One subpopulation produced a striking time-dependent valence switch: initial aversion gave way to approach over approximately ten minutes of operant engagement. This switch required both dopamine and active behavioral contingency, demonstrating that agency itself is a necessary condition for such a valence switch. Together, our results suggest that individual DANs function as specialized, context-sensitive reporters for specific goals rather than general-purpose value signals, and that their apparent generality under some circumstances may reflect the consequences of non-contingent DAN stimulation rather than a true unified valence code.