Hierarchical architecture of dopaminergic circuits enables second-order conditioning in Drosophila

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eLife. 2023 Jan 24;. doi: 10.7554/eLife.79042

Hierarchical architecture of dopaminergic circuits enables second-order conditioning in Drosophila Funke LabAso LabFlyLightInvertebrate Shared Resource

Yamada Daichi, Bushey Daniel, Feng Li, Hibbard Karen, Sammons Megan, Funke Jan, Litwin-Kumar Ashok, Hige Toshihide, Aso Yoshinori

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Abstract

Dopaminergic 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.