Abstract
Forgetting is increasingly recognized as an active adaptive process, yet its mechanism remains elusive at the cellular and synaptic levels. Here, we show that the natural decay of hours-scale memory in Drosophila is promoted through shifting memory traces between distinct synaptic ensembles. Aversive conditioning produces an initial memory trace of presynaptic depression primarily confined to the γ1 compartment, one of five axonal compartments of γ Kenyon cells, that drives avoidance behavior. The memory trace later is shifted to the γ4 compartment, but is encoded as presynaptic potentiation. This shift is initiated by Rac1/Dia activation, which rapidly adds active zones (AZs), followed by Ephrin-dependent AZ elimination in the γ4 compartment, promoting decay. Preventing this shift preserves γ1 memory trace for over 1 day without forgetting. Thus, forgetting is achieved by shifting memory trace from early, more persistent presynaptic depression to new synaptic ensemble-encoded presynaptic potentiation prone to accelerated memory decay.
