Disruption of α′/β′ MBNs impairs new memories while leaving remote memories in the same animal intact. A, Diagram illustrating the appetitive conditioning protocol used in this experiment. Flies carrying one copy of c305a-gal4, tub-gal80ts, and uas-kir2.1 were raised and then starved at 18°C for 28 h. Flies were then trained using forward appetitive olfactory conditioning with Oct and Mch at 24°C (training A). They were fed immediately after training for 12 h and then starved again for 12 h before training B at 24°C with a second odor combination, Ben and Mes. They were then tested for memory of the first odor combination or the second. The experimental group was incubated at 30°C for 6 h before the second training experience to allow the expression of Kir2.1 and the silencing of the α′/β′ MBNs. The control group was kept at 18°C during this 6 h incubation period. B, Inactivating the α′/β′ MBNs severely impaired expression of “recent” memory (training B) (Mann–Whitney pairwise comparison, p ≤ 0.0022). Flies containing only c305a-gal4;gal80ts, or uas-kir2.1 exhibited unaltered expression of memory from training B (Mann–Whitney pairwise comparisons, p ≥ 0.6304). Asterisks indicate a statistically significant difference (n = 6 for each group). C, Inactivating the α′/β′ MBNs had no significant effect on the expression of “remote” memory (training A; Mann–Whitney pairwise comparison, p = 0.6298). Flies containing only c305a-gal4;gal80ts or uas-kir2.1 exhibited unaltered expression of memory from training A (Mann–Whitney pairwise comparisons, p ≥ 0.2607). Asterisks indicate a statistically significant difference (n = 6 for each group). D, Inactivating the α/β MBNs impaired expression of “recent” memory (training B; Mann–Whitney pairwise comparison, p = 0.0159). Flies containing only R28H05-gal4;gal80ts or uas-kir2.1 exhibited unaltered expression of memory from training B (Mann–Whitney pairwise comparisons, p ≥ 0.2971). Asterisks indicate a statistically significant difference (n = 6 for each group). E, Inactivating the α/β MBNs significantly impaired the expression of “remote” memory (training A; Mann–Whitney pairwise comparison, p = 0.0129). Flies containing only R28H05-gal4;gal80ts or uas-kir2.1 exhibited unaltered expression of memory from training A (Mann–Whitney pairwise comparisons, p ≥ 0.2403). Asterisks indicate a statistically significant difference (n = 6 for each group). F, Drosophila-adapted, standard model of system consolidation. STM is encoded in all three classes of MBNs. During system consolidation, memory traces are shifted from the three classes of MBNs so that LTM becomes the exclusive property of the α/β MBNs. The consolidation process is mediated in part by the dorsal paired medial (DPM) neurons. Dopaminergic neurons (DA) carry out active forgetting from all sets of neurons.