SUMMARYAnimals form and update learned associations between otherwise neutral cues and aversive outcomes to predict and avoid danger in changing environments. When a cue later occurs without punishment, this unexpected withdrawal of aversive outcome is encoded as reward, via activation of reward-encoding dopaminergic neurons. Using real-time in vivo functional imaging, optogenetics, behavioral analysis, and electron-microscopy, we identify the neural mechanism through which Drosophila reward-encoding dopaminergic neurons are activated when an olfactory cue is unexpectedly no longer paired with electric shock punishment. Reduced activation of punishment-encoding dopaminergic neurons relieves depression of synaptic inputs to cholinergic neurons, which in turn synaptically increase odor responses of reward-encoding dopaminergic neurons to decrease odor avoidance. These studies reveal for the first time how an indirect excitatory cholinergic synaptic relay from punishment- to reward-encoding dopaminergic neurons encodes the absence of a negative as a positive, revealing a general circuit motif for unlearning aversive memories that could be present in mammals.
Cholinergic relay from punishment- to reward-encoding dopamine neurons signals punishment withdrawal as reward in Drosophila
