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.

Reactivating Hippocampal-Mediated Memories During Reconsolidation to Disrupt Fear

“…We believe our manipulation works similarly to other stimulation- based interference protocols associated with neural plasticity such as electroconvulsive therapy (ECT), deep-brain stimulation, or trans-magnetic stimulation. While there is a paucity of literature on these treatments in the context of conditioned fear with mixed effects reported 52 , it is possible the timing of the manipulation is a key factor for treatment efficacy. For instance, stimulation occurring concurrently with recall of the fear memory may provide a unique window of opportunity to leverage reconsolidation mechanisms.…”

Reactivating Hippocampal-Mediated Memories to Disrupt the Reconsolidation of Fear

“…While these mice did not have this experience reactivated, they still experienced a reduction in fear. In humans, there is evidence to show that trait positive affect can protect against stress influencing health outcomes 52 , an effect known as the undoing hypothesis 29 . In line with this hypothesis, these results suggest hippocampal involvement in processing emotional memory may contribute to its regulation of stress responses.…”

A critical assessment of reconsolidation interference as a tool for therapeutic forgetting

“…It has been suggested that not all behavioral effects observed after combining a reminder with an amnestic manipulation can be attributed to reconsolidation interference (7)(8)(9)(10)(11)(12)(13)(14). In addition, there has been a considerable amount of failures to conceptually or exactly replicate previously published studies that appeared to demonstrate memory reconsolidation (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) and reconsolidation theory presently cannot illuminate which factors explain those negative results.…”

“…Some researchers found amnesia when electroconvulsive shock was given after re-exposure to a previously conditioned tone, e.g., (2,80), whereas others did not, e.g., (19,20). Similarly, influential findings from studies with human participants showing reminder-dependent attenuation of fear memories, e.g., (81)(82)(83), or episodic memories, e.g., (84), have failed to replicate, e.g., (16,21,25).…”