Activity of defined mushroom body output neurons underlies learned olfactory behavior in Drosophila

Summary During olfactory learning in fruit flies, dopaminergic neurons assign value to odor representations in the mushroom body Kenyon cells. Here we identify a class of downstream glutamatergic mushroom body output neurons (MBONs) called M4/6, or MBON-β2β′2a, MBON-β′2mp, and MBON-γ5β′2a, whose dendritic fields overlap with dopaminergic neuron projections in the tips of the β, β′, and γ lobes. This anatomy and their odor tuning suggests that M4/6 neurons pool odor-driven Kenyon cell synaptic outputs. Like that of mushroom body neurons, M4/6 output is required for expression of appetitive and aversive memory performance. Moreover, appetitive and aversive olfactory conditioning bidirectionally alters the relative odor-drive of M4β′ neurons (MBON-β′2mp). Direct block of M4/6 neurons in naive flies mimics appetitive conditioning, being sufficient to convert odor-driven avoidance into approach, while optogenetically activating these neurons induces avoidance behavior. We therefore propose that drive to the M4/6 neurons reflects odor-directed behavioral choice.
Highlights • Glutamatergic mushroom body output neurons are required for memory expression • Training bidirectionally alters relative odor drive to output neurons • Blocking glutamatergic mushroom body output neurons mimics appetitive conditioning • Optogenetic activation drives avoidance behavior
Fruit fly olfactory memory involves mushroom body plasticity. Owald et al. identified glutamatergic mushroom body output neurons that are critical for memory expression. Conditioning bidirectionally alters odor drive to these outputs. Blocking them mimics appetitive conditioning, whereas activation induces avoidance behavior.