0/UAS-RFP;TH-gal4 flies. Remarkably, and in agreement with our behavioral results, we found robust, ongoing Ca2+-based activity within the MP1 and MV1 DAN processes that innervate the MBs, while the V1 innervation of the MBs was silent ( Figures 5A–5C). Additionally, we observed that the DAN innervations of the anterior inferior medial protocerebrum (aimpr) (innervated extensively by MP1 and MV1 DANs; Tanaka et al., 2008) also displayed robust activity. Importantly, learning did not alter DAN activity in any of these regions

as neither forward nor backward conditioning caused significant alterations to the overall activity per second. Interestingly, while simultaneously recording multiple regions, we observed selleck screening library that the ongoing activity appeared highly synchronized between MP1, MV1, and the aimpr ( Figure 5B). We calculated a normalized cross-correlation between simultaneously recorded signals between these regions ( Figure 5D) and found that the MP1, MV1, and aimpr activities were highly correlated, while V1 was see more not. Behavioral conditioning did not significantly alter the activity correlations. These data, along with our blocking experiments (Figures 1A, 1B, and 2B), demonstrate that the MP1 and MV1 DANs have ongoing activity and that the MBs receive continued

dopaminergic input after memory acquisition. Furthermore, this forgetting signal is synchronized between these two DANs. We reasoned that if dopamine is mediating forgetting of memory stored within the MBs, then loss of dopamine receptors expressed in the MBs would block this forgetting pathway. Both the dDA1 and DAMB dopamine receptors are highly expressed within the MBs (Han et al., 1996 and Kim et al., 2003). However, because dDA1 mutants do not form aversive olfactory memories due to the dDA1 role in acquisition ( Kim et al., 2007),

we chose to look at the potential role for DAMB in forgetting. L-NAME HCl Remarkably, we found that despite a slightly decreased immediate memory, damb mutants exhibited significantly enhanced memory retention at time points up to 24 hr, a time at which memory in control Canton-S flies was completely forgotten ( Figure 6A). This more persistent increase in memory expression with the complete loss of DAMB compared to that observed after transiently blocking synaptic activity of DANs ( Figures 3A–3A″) is probably due to the constitutive disruption of the dopamine signaling pathway across the entire retention window. We wondered also whether, in addition to gradual forgetting during memory retention, DAMB also played a role in the acute forgetting that occurs during reversal learning ( Shuai et al., 2010). It has been shown that if flies are trained to one odor pair, then immediately trained to the reverse CS+/CS− contingency, they exhibit a stronger preference for the most recent and reversed contingency when subsequently tested.