Dopamine Neurons Mediate Learning and Forgetting through Bidirectional Modulation of a Memory Trace

Summary: It remains unclear how memory engrams are altered by experience, such as new learning, to cause forgetting. Here, we report that short-term aversive memory in Drosophila is encoded by and retrieved from the mushroom body output neuron MBOn-γ2α′1. Pairing an odor with aversive electric shock creates a robust depression in the calcium response of MBOn-γ2α′1 and increases avoidance to the paired odor. Electric shock after learning, which activates the cognate dopamine neuron DAn-γ2α′1, restores the response properties of MBOn-γ2α′1 and causes behavioral forgetting. Conditioning with a second odor restores the responses of MBOn-γ2α′1 to a previously learned odor while depressing responses to the newly learned odor, showing that learning and forgetting can occur simultaneously. Moreover, optogenetic activation of DAn-γ2α′1 is sufficient for the bidirectional modulation of MBOn-γ2α′1 response properties. Thus, a single DAn can drive both learning and forgetting by bidirectionally modulating a cellular memory trace. : In Drosophila, dopamine neurons regulate both learning and forgetting. Berry et al. identify a locus for the storage and retrieval of a short-term memory trace and show that a single dopamine neuron regulates both formation and disruption of this trace. These findings elucidate circuit mechanisms underlying memory storage and removal. Keywords: forgetting, memory updating, memory trace, dopamine neuro