Three Dopamine Pathways Induce Aversive Odor Memories with Different Stability

Animals acquire predictive values of sensory stimuli through reinforcement. In the brain of Drosophila melanogaster, activation of two types of dopamine neurons in the PAM and PPL1 clusters has been shown to induce aversive odor memory. Here, we identified the third cell type and characterized aversive memories induced by these dopamine neurons. These three dopamine pathways all project to the mushroom body but terminate in the spatially segregated subdomains. To understand the functional difference of these dopamine pathways in electric shock reinforcement, we blocked each one of them during memory acquisition. We found that all three pathways partially contribute to electric shock memory. Notably, the memories mediated by these neurons differed in temporal stability. Furthermore, combinatorial activation of two of these pathways revealed significant interaction of individual memory components rather than their simple summation. These results cast light on a cellular mechanism by which a noxious event induces different dopamine signals to a single brain structure to synthesize an aversive memory. Punishment not only repels animals but also drives the formation of aversive memory of contiguous stimuli. Guided by the memory, animals can later avoid the cues that predict negative outcome. How is a punishing event represented in the brain? We have found that at least three types of dopamine neurons in the Drosophila brain contribute to memory formation. Genetic activation of these neurons temporally paired with an odor presentation induced aversive odor memory, raising a question about the functional distinction of these neurons. Here we characterized aversive memories induced by these dopamine neurons. The magnitude of immediate memory and following memory decay differ greatly among the three cell types. Interestingly, combinatorial activation of two cell types revealed that induced memory is not a simple sum of the two memories, but rather the result of non-linear interaction specific for different retention times. Taken together, we propose that a punishing event induces aversive memory with unique temporal dynamics by tuning the activation of selective dopamine neurons.