Visceral signaling of post-ingestive malaise directs memory updating in Drosophila

Consolidation is a time when labile memories transition to a stable form. Malaise learning in Drosophila reveals consolidation to also permit memory updating. Flies taught to associate one of two odors with toxin-tainted sugar initially express conditioned odor approach, that following consolidation switches to avoidance. Behavioral reversal emerges from dopaminergic update of parallel memories for the two trained odors. Differential serotoninergic modulation of specific aversive and rewarding dopaminergic neuron subtypes permits post-ingestive intoxication to suppress consolidation of initial odor-sugar memory and simultaneously invert reward memory plasticity into "safety" memory for the odor experienced without food. Fat body release of the Toll-ligand activating protease modSP, and resilience factor Turandot A, instruct malaise updates by triggering autocrine Toll signaling in the same brain dopaminergic neurons that form and consolidate initial sugar memory. This neural mechanism overcomes the credit assignment problem of delayed post-ingestive reinforcement by updating earlier memories of the trained odors.