The role and dynamic of strengthening in the reconsolidation process in a human declarative memory: what decides the fate of recent and older memories?

Abstract

Several reports have shown that after specific reminders are presented, consolidated memories pass from a stable state to one in which the memory is reactivated. This reactivation implies that memories are labile and susceptible to amnesic agents. This susceptibility decreases over time and leads to a re-stabilization phase usually known as reconsolidation. With respect to the biological role of reconsolidation, two functions have been proposed. First, the reconsolidation process allows new information to be integrated into the background of the original memory; second, it strengthens the original memory. We have previously demonstrated that both of these functions occur in the reconsolidation of human declarative memories. Our paradigm consisted of learning verbal material (lists of five pairs of nonsense syllables) acquired by a training process (L1-training) on Day 1 of our experiment. After this declarative memory is consolidated, it can be made labile by presenting a specific reminder. After this, the memory passes through a subsequent stabilization process. Strengthening creates a new scenario for the reconsolidation process; this function represents a new factor that may transform the dynamic of memories. First, we analyzed whether the repeated labilization-reconsolidation processes maintained the memory for longer periods of time. We showed that at least one labilization-reconsolidation process strengthens a memory via evaluation 5 days after its re-stabilization. We also demonstrated that this effect is not triggered by retrieval only. We then analyzed the way strengthening modified the effect of an amnesic agent that was presented immediately after repeated labilizations. The repeated labilization-reconsolidation processes made the memory more resistant to interference during re-stabilization. Finally, we evaluated whether the effect of strengthening may depend on the age of the memory. We found that the effect of strengthening did depend on the age of the memory. Forgetting may represent a process that weakens the effect of strengthening.

Figure 1. Memory strengthening by repeated triggering of labilization-reconsolidation modified the memory persistence.

A) Experiment 1.A (n = 12). A.1) Experimental protocol. A three-day experiment. L1-TR, stands for the training session of the list of syllables (List 1; L1), Rc for the cue reminder, and L1-TS for the testing session of L1. Groups differ in the number or presence or absence of reminders that they received on Day 2. Group NR 7d without any reminder presentation, Group RcX1 received a cue reminder, Group RcX2 received two cue reminders. A.2) Testing Session. Mean number of total errors +/− SEM on Day 7. *,p<0,05. Black bar stands for Group NR 7d, Light Gray bar for Group RcX1 and White bar for Group RcX2. A.3) Error Type. A.3.1) Mean number of Void-Type error errors +/− SEM on Day 7. A.3.2) Confusion-type errors. A.3.3) Intralist-type errors. Symbols as above.

Figure 2. Strengthened memories by repeated labilization-reconsolidations are more resistant to be interfered with a second task.

A) Experiment 2.A (n = 13). A.1) Experimental protocol. A three-day experiment. Rc–L2, stands for the presentation of the cue reminder and five minutes later the acquisition of the Interference task List-2 (L2), L2-TR for the training in L2, L2-TS for the testing of that list and the remaining symbols as in Experiment 1. Groups differ in the number of reminders received and the presence or absence of the L2 list. Groups RcX1 and RcX2 as in Experiment 1. Group RcX1– L2 received a cue reminder and five minutes later learned L2 list, Group RcX2– L2 received two cue reminder and five minutes later learned L2 list, Group CT-L2 only learned L2 list on Day 2. A.2) L2 Testing Session. Mean number of total errors +/− SEM on Day 3. Black bar stands for Group CT-L2, Dark Gray bar for Group RcX1-L2 and Stripe bar for Group RcX2-L2. A.3) L1 Testing Session. Mean number of total errors +/− SEM on Day 3. *, p<0,05. Symbols as in Experiment A.2 and Experiment 2 A.2. A.4) Error Type. A.4.1) Mean number of Void-Type error errors +/− SEM on Day 7. A.4.2) Confusion-type errors. A.4.3) Intralist-type errors. Symbols as above.

Figure 3. Successive labilization-reconsolidation processes do not strengthen older declarative memory.

A) Two or four cue-reminders do not improve performance on Day 8. Experiment 3.A (n = 10). A.1) Experimental protocol. A three-day experiment. Symbols as in Experiment 1.A. Groups differ in the number or presence of reminders that they received on Day 7. Group NR 8d received no reminder, RcX4 received the cue reminder four times, Groups RcX1 and RcX2 as in Experiment 1.A. A.2) Testing Session. Mean number of total errors +/− SEM on Day 8. Black bar stands for Group NR 8d, Light Gray bar for Group RcX1, White bar for RcX2, and Stripe gray bar for Group RcX4. A.3) Error Type. A.3.1) Mean number of Void-Type error errors +/− SEM on Day 7. A.3.2) Confusion-type errors. A.3.3) Intralist-type errors. Symbols as above. B) Older memories are subject to change by forgetting compromising the effect of the interference. Experiment 3B (n = 10). B.1) Experimental protocol. A three-day experiment. Symbols as above. B.2) L2 Testing Session. Mean number of total errors +/− SEM on Day 8. Black bar stands for Group CT-L2, Dark Gray bar for Group RcX1-L2. B.3) L1 Testing Session. Mean number of total errors +/− SEM on Day 8, Black bar stands for NR 8d and Dark gray for RcX1-L2. B.4) Error Type. B.4.1) Mean number of Void-Type error errors +/− SEM *, p<0,05. on Day 8. B.4.2) Confusion-type errors. B.4.3) Intralist-type errors. Symbols as above.

Figure 4. Experimental Protocol.

A) Actual trial. It was formed by the context period: specific combination of a light (color illumination of the room), image (a picture on the monitor) and sound (music melody from earphones); and by a syllable period: six seconds after the stimuli presentation, five pairs of cue-response syllables were presented successively and in random order. B) Paired-associated memory. The List1 and List2 list presented in the training and testing sessions. C) Types of reminders. (Top diagram) The cue reminder (Rc) included the specific context, subjects had to press the expectancy keys (YES-NO), then one cue-syllable was presented after which the trial was abruptly interrupted, thus not allowing the subject to answer with the respective response-syllable. (Middle diagram) The context reminder (Rctx) consisted of the presentation of specific context, subjects had to press the expectancy keys (YES-NO) and the trial was abruptly interrupted before any syllable presentation. (Bottom diagram). Scissors stand for the full-stop of each type of reminder.