Post-retrieval effects of icv infusions of hemicholinium in mice are dependent on the age of the original memory

Abstract

CF-1 male mice were trained in an inhibitory avoidance task using a high footshock (1,2 mA, 50 Hz, 1 sec) in order to reduce the influence of extinction on retention performance. At 2, 7, 14, or 30 d after training, the first retention test was performed and hemicholinium (HC-3, 1.0 microg/mice), a specific inhibitor of high-affinity choline uptake in brain cholinergic neurons, was given intracerebroventricularly immediately after. Twenty four hours after treatment, mice were tested in an inhibitory avoidance task during five consecutive days, each 24 h apart. Retention performance was impaired by HC-3 when the first re-exposure took place at 2, 7, or 14 d, but the effect was no longer seen when re-exposure occurred 30 d after training. We did not find spontaneous recovery 21 d after training, when memory was retrieved 2 d after training and HC-3 was given immediately after. Although we cannot definitively discard a retrieval deficit, this lack of spontaneous recovery is in accordance with the storage-deficit interpretation. These results confirm and extend previous ones, suggesting that central cholinergic mechanisms are involved in the hypothetical reconsolidation memory processes of an inhibitory avoidance task in mice and also suggest that this participation depends on the "age" of the original memory trace. This implies that the vulnerability of a reactivated memory to a specific treatment, as the one used in this study, inversely correlates with the age of the original memory, and it is likely to determine memory reconsolidation processes.

Figure 1.

Effect of icv infusion of SS (1 μL) or HC-3 (1 μg/μL) given immediately after memory reactivation on retention performance at different training-memory reactivation test intervals. Each bar represents the medians and interquartile ranges (n = 15 mice/group, shocked mice) (A) 2 d; (B) 7 d; (C) 14 d; (D) 30 d. Test numbers represent successive test. Six retention tests were given, with an interval of 24 h between tests. **P < 0.01, in all cases compared with its respective test number 2 (Mann-Whitney U-test, two tailed), #P < 0.05, in all cases compared with its respective test number when memory was evaluated 2 or 7 d after training (A, B) (Mann-Whitney U-test, two tailed). The behavioral experimental scheme is found above the graphs.

Figure 2.

Long lasting effects of icv infusion of HC-3 (1 μg/μL) on retention performance after memory reactivation. Each bar represents the medians and interquartile ranges. (TR, training) (n = 15 mice/group). (A) Mice were tested only 21 d after training. (B) Mice were tested twice (48 h and 21 d) after training. **P < 0.01, in all cases with respect to first retention trial (Mann-Whitney U-test, two tailed). The behavioral experimental scheme is found above the graphs.