Dopamine is synonymous with reward in mammals but associated with aversive reinforcement in insects, where reward seems to be signalled by octopamine; here it is shown that flies have discrete populations of dopamine neurons representing positive or negative values that are coordinately regulated by octopamine. The neurotransmitter dopamine has been synonymous with reward in mammals, but is associated with aversive reinforcement in insects. In insects, it was thought, reward was signalled by octopamine. Now Scott Waddell and colleagues show that flies have discrete 'negative' and 'positive' populations of dopamine neurons, which are coordinately regulated by octopamine. This work reconciles previous findings with octopamine and dopamine, and suggests that reinforcement systems in flies are more like those in mammals than previously thought. Dopamine is synonymous with reward and motivation in mammals1,2. However, only recently has dopamine been linked to motivated behaviour and rewarding reinforcement in fruitflies3,4. Instead, octopamine has historically been considered to be the signal for reward in insects5,6,7. Here we show, using temporal control of neural function in Drosophila, that only short-term appetitive memory is reinforced by octopamine. Moreover, octopamine-dependent memory formation requires signalling through dopamine neurons. Part of the octopamine signal requires the α-adrenergic-like OAMB receptor in an identified subset of mushroom-body-targeted dopamine neurons. Octopamine triggers an increase in intracellular calcium in these dopamine neurons, and their direct activation can substitute for sugar to form appetitive memory, even in flies lacking octopamine. Analysis of the β-adrenergic-like OCTβ2R receptor reveals that octopamine-dependent reinforcement also requires an interaction with dopamine neurons that control appetitive motivation. These data indicate that sweet taste engages a distributed octopamine signal that reinforces memory through discrete subsets of mushroom-body-targeted dopamine neurons. In addition, they reconcile previous findings with octopamine and dopamine and suggest that reinforcement systems in flies are more similar to mammals than previously thought.

Layered reward signalling through octopamine and dopamine in Drosophila