A Neural Circuit Arbitrates between Persistence and Withdrawal in Hungry Drosophila

In pursuit of food, hungry animals mobilize significant energy resources and overcome exhaustion and fear. How need and motivation control the decision to continue or change behavior is not understood. Using a single fly treadmill, we show that hungry flies persistently track a food odor and increase their effort over repeated trials in the absence of reward suggesting that need dominates negative experience. We further show that odor tracking is regulated by two mushroom body output neurons (MBONs) connecting the MB to the lateral horn. These MBONs, together with dopaminergic neurons and Dop1R2 signaling, control behavioral persistence. Conversely, an octopaminergic neuron, VPM4, which directly innervates one of the MBONs, acts as a brake on odor tracking by connecting feeding and olfaction. Together, our data suggest a function for the MB in internal state-dependent expression of behavior that can be suppressed by external inputs conveying a competing behavioral drive. [Display omitted] •Hunger motivates persistent food odor tracking even without reward•Two synaptically connected MBONs, -γ1pedc>αβ and -α2sc, regulate odor tracking•Octopamine neurons connect feeding and counteract MBON and odor tracking•Dopaminergic neurons and Dop1R2 signaling promote persistent tracking What drives behavioral persistence versus quitting? Sayin et al. propose that circuit modules in the fly’s learning center and dopamine drive gradually increasing food odor tracking, which can be efficiently suppressed by extrinsic, but directly innervating, feeding-related neuromodulatory neurons.