Olfactory learning skews mushroom body output pathways to steer behavioral choice in Drosophila

•Dopamine neurons coding opposite value are segregated in the fly brain.•Dopamine neurons representing reward type innervate discrete mushroom body areas.•Mushroom body output neurons are specific to dopaminergic reinforcement zones.•Olfactory learning skews different collections of mushroom body output junctions.•Mushroom bodies are fan-in fan-out circuits like the cerebellum and hippocampus.

Learning permits animals to attach meaning and context to sensory stimuli. How this information is coded in neural networks in the brain, and appropriately retrieved and utilized to guide behavior, is poorly understood. In the fruit fly olfactory memories of particular value are represented within sparse populations of odor-activated Kenyon cells (KCs) in the mushroom body ensemble. During learning reinforcing dopaminergic neurons skew the mushroom body network by driving zonally restricted plasticity at synaptic junctions between the KCs and subsets of the overall small collection of mushroom body output neurons. Reactivation of this skewed KC-output neuron network retrieves memory of odor valence and guides appropriate approach or avoidance behavior.