Two Parallel Pathways Assign Opposing Odor Valences during Drosophila Memory Formation

During olfactory associative learning in Drosophila, odors activate specific subsets of intrinsic mushroom body (MB) neurons. Coincident exposure to either rewards or punishments is thought to activate extrinsic dopaminergic neurons, which modulate synaptic connections between odor-encoding MB neurons and MB output neurons to alter behaviors. However, here we identify two classes of intrinsic MB γ neurons based on cAMP response element (CRE)-dependent expression, γCRE-p and γCRE-n, which encode aversive and appetitive valences. γCRE-p and γCRE-n neurons act antagonistically to maintain neutral valences for neutral odors. Activation or inhibition of either cell type upsets this balance, toggling odor preferences to either positive or negative values. The mushroom body output neurons, MBON-γ5β′2a/β′2mp and MBON-γ2α′1, mediate the actions of γCRE-p and γCRE-n neurons. Our data indicate that MB neurons encode valence information, as well as odor information, and this information is integrated through a process involving MBONs to regulate learning and memory. [Display omitted] •Mushroom body γ Kenyon cells consist of γCRE-p and γCRE-n cells encoding preferences•γCRE-p cells are required for aversive associations and inhibit attraction•γCRE-n cells are required for appetitive associations and inhibit aversion•MBON-γ5 and -γ2 neurons mediate actions of γCRE-p and γCRE-n neurons Aversive and appetitive olfactory memories in fruit flies are formed in third order olfactory neurons, the mushroom body Kenyon cells (KCs). Yamazaki et al. identify parallel pathways consisting of two subpopulations of KCs and their output neurons that encode aversive and appetitive valences.