Disruption of olfactory learning and LTM consolidation by acute induction of anti-dNR1 mRNA. EP331 flies contain EP elements inserted downstream of and in an opposite orientation to the transcription start site of dNR1. The EP element yields a specific anti-dNR1 transcript [33] in the presence of GAL4, a yeast transcription factor that binds to its target sequence, UAS (upstream activation sequence, constructed in the EP element [150]), then activates transcription of the downstream gene [151], HS-GAL4 flies contain a GAL4 transgene under the control of a heat shock promoter. A: Learning in transheterozygous EP331, hs-GAL4/+, + (EP331/P26) flies was significantly reduced after heat shock (HS, arrowhead; 15 hr recovery time after heat shock; * P < 0.001) and was mildly lower in the absence of heat shock (–HS), compared to wild-type controls (+/+; two left panels). When tested 36 hr after heat shock, learning returned to pre-heat shock level (two right panels), suggesting that heat shock-specific disruption of learning is transient. B: Transheterozygous EP331, hs-GAL4/+, + (EP331/P26) flies were subjected to spaced (two left panels) or massed (two right panels) training (gray arrow) [33] 15 hr after heat shock. One-day memory after spaced training was significantly disrupted (* P < 0.05) and was normal after massed training. One-day memory after spaced training in EP331, hs-GAL4/+, + flies, in fact, was reduced 47% to a level similar to normal one-day memory after massed training. Typically, one-day memory after spaced training consisted of 50% LTM and 50% ARM (anesthesia-resistant memory). LTM was specifically disrupted in transgenic flies inducibly overexpressing CREB repressor; one-day memory after massed training contained only ARM [96]. These results suggest that ARM is normal and LTM is completely abolished in EP331/+, hs-GAL4/+ flies after acute disruption of dNR1. (Source: Adapted from Xia, S. et al., Curr. Biol., 15, 603, 2005. With permission.)