Aversive learning hijacks a brain sugar sensor to consolidate memory

The formation of food-related memories involves post-ingestion nutrient sensing signals^1-5. 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 cues^7,8. 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 thyrostimulin^10,11, 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.