P.2.048 - On the synaptic tagging and capture hypothesis and the process of memory reconsolidation

Abstract

The Synaptic Tagging and Capture (STC) hypothesis proposes that a strong stimulation of a synaptic pathway leads to two dissociable events: (a) local tag setting and (b) the synthesis of diffusible plasticity-related proteins (PRPs) [1]. The PRPs are then “captured” by the tagged synapses allowing the sustenance of long-term potentiation (LTP). Recent behavioral studies suggest that long-term memory (LTM) may also require both synaptic tagging and PRP synthesis in order to persist [2,3]. The studies show that weak events, only able to induce short-term memory (STM), could lead to LTM when the training was associated with parallel stronger experience (i.e. capable of inducing the synthesis of PRPs). Here we investigate whether the process of labilization and reconsolidation of a memory could also involve a mechanism of Synaptic Tagging and Capture. More specifically, for the pilot study presented here (n = 5-8), we aimed to evaluate whether the amnesic effect of the NMDAr inhibitor, MK-801, upon the reactivation of a contextual fear memory (CFC), could be prevented by pairing the event with a strong experience (exposure to novel environment). For that, adult male long-evans rats (200–300g), co-housed in groups of 4 per cage, under a 12 h light/dark cycle and at temperature of 24 C, with water and food ad libitum were used, in accordance to local and national animal care guidelines. On day one, rats were placed in the CFC chamber for 3 min, received 2 foot shocks (0.7 mA 1.5 sec), separated by a 30-sec interval, and after 1 min, rats returned to their home cages. Two days later, animals on the experimental group were exposed to a novel arena (control animals remained on homecages) and one hour later were reexposed to the CFC context (5 min). MK-801 or Saline was injected intraperitoneally (1mg/kg) immediately after. On the next day, all animals were exposed once more to the CFC context (4 min) in order to assess memory expression. The aversive response (freezing) were recorded during all sessions and used as the memory index. Two-way ANOVA revealed marginal effect of drug (p = 0.08; Saline x MK-801), a significant effect of group (p= 0.02; Control x Novelty) and no interaction (p = 0.22; Drug x Group). Further analysis with Tukey post-hoc revealed a significant difference between the animals not exposed to novelty and treated with MK-801, and those treated with MK-801 as well, but previously exposed to novelty (p = 0.03). The results are still preliminary, but indicate that the exposure to a novel experience (supposedly capable of inducing PRPs synthesis in Hippocampus) is able to prevent the effects associated to amnesic treatment after the reactivation of a contextual fear memory. This associative phenomenon could be the first step suggesting the involvement of a Synaptic Tagging and Capture mechanism in process of memory labilization and reconsolidation.