Forgetting Is Regulated By Rac Activity In Drosophila

Initially acquired memory dissipates rapidly if not consolidated. Such memory decay is thought to result either from the inherently labile nature of newly-acquired memories or from interference by subsequently attained information. However, little is known about the biological process underlying forgetting. Here, we investigate forgetting in Drosophila through a behavioral genetic approach, and find that forgetting is regulated through small G protein Rac. Inhibition of Rac activity by induced expression of a dominant-negative form leads to slower decay of early memory, extending it from a few hours to more than one day, and to blockade of interference-induced forgetting. Conversely, elevation of Rac activity by expression of a consititutively active form in mushroom body neurons accelerates memory decay. The Rac-forgetting mechanism does not affect memory acquisition and is independent of Rutabaga adenylyl cyclase-mediated memory formation mechanisms. Experience-dependent endogenous Rac activation is evoked on different time scales, corresponding to gradual memory loss in passive memory decay and acute memory removal in reversal learning. We also show that Rac inhibition results in abolished behavioral flexibility in reversal learning, suggesting forgetting as an adaptive strategy in a changing behavioral context. Finally, during examination of Rac's role in trace conditioning, we find that Rac also regulates rapid decay of the non-reinforced sensory storage of olfactory stimuli. Taken together, the results demonstrate a key role for Rac in forgetting and also imply that actin cytoskeleton remodeling may contribute to memory erasure.