%AYamada, Daichi%ABushey, Daniel%ALi, Feng%AHibbard, Karen%ASammons, Megan%AFunke, Jan%ALitwin-Kumar, Ashok%AHige, Toshihide%AAso, Yoshinori%BJournal Name: eLife; Journal Volume: 12 %D2023%I %JJournal Name: eLife; Journal Volume: 12 %K %MOSTI ID: 10398027 %PMedium: X %THierarchical architecture of dopaminergic circuits enables second-order conditioning in Drosophila %XDopaminergic neurons with distinct projection patterns and physiological properties compose memory subsystems in a brain. However, it is poorly understood whether or how they interact during complex learning. Here, we identify a feedforward circuit formed between dopamine subsystems and show that it is essential for second-order conditioning, an ethologically important form of higher-order associative learning. The Drosophila mushroom body comprises a series of dopaminergic compartments, each of which exhibits distinct memory dynamics. We find that a slow and stable memory compartment can serve as an effective ‘teacher’ by instructing other faster and transient memory compartments via a single key interneuron, which we identify by connectome analysis and neurotransmitter prediction. This excitatory interneuron acquires enhanced response to reward-predicting odor after first-order conditioning and, upon activation, evokes dopamine release in the ‘student’ compartments. These hierarchical connections between dopamine subsystems explain distinct properties of first- and second-order memory long known by behavioral psychologists. %0Journal Article