Aversive learning hijacks a brain sugar sensor to consolidate memory

The formation of food-related memories involves post-ingestion nutrient sensing signals1–5. Whether nutrient sensors act beyond feeding-relevant behaviour is less well understood. Here we show that an internal sugar sensor in the Drosophila brain6 is involved in memory consolidation, both in fasted flies subjected to an appetitive learning task involving a sucrose reward and in flies fed ad libitum subjected to an aversive learning task independent of food cues7,8. In the latter, spaced repetition of learning sessions, a prerequisite to induce long-term memory, lures brain fructose-sensing neurons into a fasted state through a disinhibition mechanism that transiently restores their sensing ability despite satiation9. Post-learning sugar ingestion activates disinhibited fructose-sensing neurons, which triggers memory consolidation through the release of the glycoprotein hormone thyrostimulin10,11, as in appetitive learning. The reset of fructose-sensing neurons by spaced training also results in a fasted state-like feeding behaviour, manifesting in a strong increase in sucrose preference and intake. By revealing a mechanism of non-homeostatic hunger and its critical relevance for memory consolidation, our results provide a neural circuit basis, and a cognitive value, to a behaviour akin to emotional eating. A study in Drosophilareveals a mechanism of non-homeostatic hunger and its critical relevance for memory consolidation.