Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.22.165209v1?rss=1 Authors: McCurdy, L. Y., Sareen, P., Davoudian, P., Nitabach, M. Abstract: Animals form and update learned associations between 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 dopaminergic neurons. Using 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. 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. Copy rights belong to original authors. Visit the link for more info