, 2009). Paip2a−/− mice performed better in this task than WT littermates ( Figure 2F). We found no differences between the two genotypes in the novel object recognition task (
Figure 2G), which examines recognition memory. Taken together, our data indicate that Paip2a−/− mice display enhanced spatial learning and memory as compared to WT littermates. To study memory consolidation, we used contextual fear conditioning, a hippocampal-dependent task that engenders robust protein synthesis-dependent long-term memory for a training context following a single session of pairing the context to a foot shock (Kelleher et al., 2004b). Since a weak stimulation (1HFS) in Paip2a−/− slices elicited L-LTP, we first examined the SCH 900776 price effect of training using a weak experimental paradigm (single 0.3 mA foot shock for 1 s). Long-term contextual fear memory was assessed 24 hr later by reintroducing the mice to the training context. Paip2a−/− mice froze significantly more than WT littermates (WT: 32.6% ± 3.1%; Paip2a−/−: 46.76% ± 4.0%, p < 0.05; Figure 2H), indicating an enhancement of long-term memory. No difference in freezing between the two groups was found 1 hr after the training, demonstrating that the acquisition of the task was intact ( Figure S3A). To rule out possible nonspecific effects of nociceptive sensitivity or motor ability, we examined pain
sensation in the radiant heat paw withdrawal ( Figure S3B) and von Frey tests ( Figure S3C) and motor coordination in the rotarod test ( Figure S3D). No differences between Paip2a−/− Dolutegravir concentration and WT mice in these assays
were observed. Next, we assessed long-term memory of Paip2a−/− mice using pairing of context to a strong foot shock (strong training, two foot shocks of 0.5 mA for 2 s separated by 1 min). Paip2a−/− mice exhibited reduced freezing 24 hr after strong training, thus demonstrating an impairment of long-term contextual memory ( Figure 2I). Freezing 1 hr after strong training was not altered, demonstrating intact acquisition ( Figure S3E). Extinction of contextual fear memories in Paip2a−/− mice was impaired as well ( Figure S3F). We also assessed cued associative memory of Paip2a−/− mice using auditory from fear conditioning, an amygdala-dependent task that leads to association of the tone with the foot shock, with weak and strong training protocols ( Costa-Mattioli et al., 2005). No difference in freezing in response to the tone was detected 24 hr after training ( Figures S3G and S3H), demonstrating that long-term auditory fear memory is not altered in Paip2a−/− mice. Taken together, these results show that hippocampus-dependent long-term memory is enhanced in Paip2a−/− mice as compared to their WT littermates following weak training and is impaired after strong training.