Electroconvulsive Shock Does Not Impair the Reconsolidation of Cued and Contextual Pavlovian Threat Memory

Abstract

Existing memories, when retrieved under certain circumstances, can undergo modification through the protein synthesis-dependent process of reconsolidation. Disruption of this process can lead to the weakening of a memory trace, an approach which is being examined as a potential treatment for disorders characterized by pathological memories, such as Post-Traumatic Stress Disorder. The success of this approach relies upon the ability to robustly attenuate reconsolidation; however, the available literature brings into question the reliability of the various drugs used to achieve such a blockade. The identification of a drug or intervention that can reliably disrupt reconsolidation without requiring intracranial access for administration would be extremely useful. Electroconvulsive shock (ECS) delivered after memory retrieval has been demonstrated in some studies to disrupt memory reconsolidation; however, there exists a paucity of literature characterizing its effects on Pavlovian fear memory. Considering this, we chose to examine ECS as an inexpensive and facile means to impair reconsolidation in rats. Here we show that electroconvulsive seizure induction, when administered after memory retrieval, (immediately, after 30 min, or after 1 h), does not impair the reconsolidation of cued or contextual Pavlovian fear memories. On the contrary, ECS administration immediately after extinction training may modestly impair the consolidation of fear extinction memory.

Keywords: ECS; ECT; consolidation; electroconvulsive shock; fear conditioning; fear extinction; reconsolidation.

Figure 1

ECS delivery after cued reactivation does not disrupt reconsolidation of an auditory fear memory. (a) Schematic outline of experimental procedures used for the cue-ECS experiments. (b,e) Reactivation graphs indicate that all groups formed an aversive memory associated with the tone. (c,f) Post-reactivation long-term memory LTM (PR-LTM) graphs show no difference in freezing between the groups resulting from ECS treatment. (d,g) A within-subjects comparison showed no change in any group across days. (h–j) Modifying the duration of the reactivating tone and session prior to ECS does not result in amnesia either. *** p < 0.001, **** p < 0.0001, error bars = standard error of the mean (SEM). Horizontal bar = PR-LTM mean. “Pre-tone” is defined as the acclimation period during reactivation, prior to the tone presentation.

Figure 2

ECS delivery after contextual reactivation does not disrupt reconsolidation of a contextual fear memory. (a) Schematic outline of experimental procedures for the context-ECS experiments. All animals acquired an aversive contextual memory, as measured at reactivation (b,e). PR-LTM freezing data for the male (c) and female (f) cohorts show no amnesia resulting from ECS. The ECS-imd and ECS-30m groups from the male cohort display significantly greater freezing than the sham group (c). A within-subjects comparison showed no change in any group across days (d,g). * p < 0.05, ** p < 0.01, **** p < 0.0001, error bars = SEM. Horizontal bar = PR-LTM mean. “Pre-training” is defined as the context acclimation period during training, prior to delivery of the tone-shock pairing.

Figure 3

ECS causes no reactivation-dependent deficits of a contextual fear memory. (a) After training, two groups were subjected to a reactivation session followed by ECS or sham stimulation, while the remaining two groups received stimulation without memory reactivation. (b) There was no difference in freezing between the groups at PR-LTM (b). Error bars = SEM.

Figure 4

ECS may modestly impair extinction learning. (a) Schematic outline of experimental procedure testing the effects of ECS on extinction learning. (b) While both groups extinguish the fear memory, the sham group may extinguish the fear faster than the ECS group. This is indicated by a reduction in statistically significant differences between pre-training (baseline) and extinction session freezing. (c) Extinction data from (b) with baseline subtraction (extinction score) for the groups on each day indicate that the ECS group continues to show high levels of freezing across days, while the sham group displays a steady decrease to baseline freezing levels, such that the difference in fear extinction between the groups is significant at EXT 2, 3, and 5. * p < 0.05, ** p < 0.01, **** p < 0.0001, error bars = SEM. “Pre-training” is defined as the context acclimation period during training, prior to delivery of the tone-shock pairing.