Linking new information to a reactivated memory requires consolidation and not reconsolidation mechanisms

Abstract

A new memory is initially labile and becomes stabilized through a process of consolidation, which depends on gene expression. Stable memories, however, can again become labile if reactivated by recall and require another phase of protein synthesis in order to be maintained. This process is known as reconsolidation. The functional significance of the labile phase of reconsolidation is unknown; one hypothesis proposes that it is required to link new information with reactivated memories. Reconsolidation is distinct from the initial consolidation, and one distinction is that the requirement for specific proteins or general protein synthesis during the two processes occurs in different brain areas. Here, we identified an anatomically distinctive molecular requirement that doubly dissociates consolidation from reconsolidation of an inhibitory avoidance memory. We then used this requirement to investigate whether reconsolidation and consolidation are involved in linking new information with reactivated memories. In contrast to what the hypothesis predicted, we found that reconsolidation does not contribute to the formation of an association between new and reactivated information. Instead, it recruits mechanisms similar to those underlying consolidation of a new memory. Thus, linking new information to a reactivated memory is mediated by consolidation and not reconsolidation mechanisms.

Figure 1. Associations Are Formed between New Information and a Reactivated Memory

Both the original and the new memory are long-lasting. Latency to enter the shock chamber was taken as a measure of memory acquisition and retention. (A) Rats trained in context A (n = 72) that received memory recall by visual CS in context B developed a strong fear memory for context B (n = 12), while both control groups (rats exposed to context B without reactivation and non-reactivated; n = 12 per group) had no memory for context B (** = p < 0.01). Rats that underwent the same training and reactivation protocol but were tested in context A (n = 12) showed retention levels similar to those of both control groups (n = 12 per group). Latencies to enter either context A or B were similar, suggesting that the new memory is as strong as the old one. (B) All groups (n = 8 per group) were re-tested 1 wk after the first test. Similar results were obtained.

Figure 2. Both the Association Formed between New and Reactivated Information and the Reactivated Original IA Memory Are Disrupted by Systemic Inhibition of Protein Synthesis

Latency to enter the shock chamber was taken as a measure of memory retention. Systemic anisomycin injection (Aniso, n = 8) immediately after visual CS reactivation in context B induced amnesia for both context A and B compared with vehicle injection (Veh, n = 8) (** = p < 0.01). Anisomycin did not affect memory of context A in rats that did not receive reactivation (n = 8, No-react).

Figure 3. C/EBPβ Is Required in the Amygdala for the Reconsolidation, but Not Consolidation, of IA Memory

Latency to enter the shock chamber was taken as a measure of memory acquisition and retention. (A) Bilateral amygdala injections of β-ODN (n = 8) 5 h after training had no effect compared to SC-ODN injection (n = 8) on IA retention tested 48 h after training. (B) Bilateral amygdala injections of β-ODN 5 h after reactivation (Test 1, n = 10) resulted in amnesia at Test 2, compared to SC-ODN injections (n = 8, * = p < 0.05).

Figure 4. Consolidation, but Not Reconsolidation, Mechanisms Are Required to Associate New Information with a Reactivated Memory

Latency to enter the shock chamber was taken as a measure of memory retention. (A) Amygdala injection of β-ODN after memory reactivation disrupted the reactivated memory without affecting the formation of an association between new information and the reactivated memory. β-ODN injection 5 h after reactivation into the amygdala of rats that underwent training in context A and memory reactivation in context B (n = 7) had no effect on the memory for context B tested 48 h after reactivation. Memory for context B was similar to that of the control group (n = 8) that received SC-ODN injection. In contrast, the same treatment strongly impaired memory of context A, compared to SC-ODN injection (** = p < 0.01). Memory of context A was not affected in rats that did not receive reactivation (n = 7). (B) Hippocampal injection of β-ODN blocked the formation of the association between new and reactivated information without affecting the stability of the reactivated memory. β-ODN injection 5 h after reactivation into the hippocampi of rats that underwent training in context A and memory reactivation in context B (n = 8) significantly impaired the retention for context B 48 h after reactivation, compared with SC-ODN injection (** = p < 0.01). β-ODN injection did not affect the memory of context A, which was similar to that of both control groups that received either SC-ODN injection after reactivation or β-ODN injection in the absence of reactivation (n = 9 for SC-ODN and n = 6 for β-ODN-injected, No-react). (C) Hippocampal injection of anisomycin blocked the formation of an association between new and reactivated information without affecting the reactivated memory. Anisomycin administration (n = 8) immediately after memory reactivation in context B significantly impaired memory of context B when tested 48 h later, compared with vehicle injection (n = 8; ** = p < 0.01). Anisomycin injection did not affect memory of context A (n = 8; ** = p < 0.01), which was similar to that of vehicle-injected control group (n = 8 per group). Anisomycin did not affect memory of context A in rats that did not receive reactivation (n = 8, No-react).