The mushroom bodies, substructures of the Drosophila brain, are involved in olfactory learning and short-term memory, but their role in long-term memory is unknown. Here we show that the alpha-lobes-absent ( ala ) mutant lacks either the two vertical lobes of the mushroom body or two of the three median lobes which contain branches of vertical lobe neurons. This unique phenotype allows analysis of mushroom body function. Long-term memory required the presence of the vertical lobes but not the median lobes. Short-term memory was normal in flies without either vertical lobes or the two median lobes studied.

Two types of consolidated memory have been described in Drosophila , anesthesia-resistant memory (ARM), a shorter-lived form, and stabilized long-term memory (LTM). Until now, it has been thought that ARM and LTM coexist. On the contrary, we show that LTM formation leads to the extinction of ARM. Flies devoid of mushroom body vertical lobes cannot form LTM, but spaced conditioning can still erase their ARM, resulting in a remarkable situation: The more these flies are trained, the less they remember. We propose that ARM acts as a gating mechanism that ensures that LTM is formed only after repetitive and spaced training.