Upon reactivation, consolidated memories can enter a temporary labile state and require restabilisation, known as reconsolidation. Interventions during this reconsolidation period can disrupt the reactivated memory. However, it is unclear whether different kinds of memory that depend on distinct brain regions all undergo reconsolidation. Evidence for reconsolidation originates from studies assessing amygdala-dependent memories using cue-conditioning paradigms in rodents, which were subsequently replicated in humans. Whilst studies providing evidence for reconsolidation of hippocampus-dependent memories in rodents have predominantly used context conditioning paradigms, studies in humans have used completely different paradigms such as tests for wordlists or stories. Here our objective was to bridge this paradigm gap between rodent and human studies probing reconsolidation of hippocampus-dependent memories. We modified a recently developed immersive Virtual Reality paradigm to test in humans whether contextual threat-conditioned memories can be disrupted by a reminder-extinction procedure that putatively targets reconsolidation. In contrast to our hypothesis, we found comparable recovery of contextual conditioned threat responses, and comparable retention of subjective measures of threat memory, episodic memory and exploration behaviour between the reminder-extinction and standard extinction groups. Our result provide no evidence that a reminder before extinction can prevent the return of context conditioned threat memories in humans.

After retrieval, reactivated memories may destabilize and require restabilization processes to persist, referred to as reconsolidation. The reminder-extinction procedure has been proposed as a behavioral reconsolidation-based intervention to persistently attenuate threat-conditioned memories. After the presentation of a single reminder trial, the conditioned threat memory may enter a labile state, and extinction training during this window can prevent the return of conditioned threat responses. However, findings on this reminder-extinction procedure are mixed and its effectiveness may be subject to boundary conditions, including memory strength. Here, we systematically investigate whether more intense threat memories are less susceptible to disruption through a reminder-extinction procedure. Using a Pavlovian auditory threat conditioning procedure at three different shock intensities, rats acquired conditioned threat responses of variable "strength." Rats subsequently underwent either extinction preceded by a reminder or standard extinction. Although different shock intensities led to different strength threat memories, all groups showed reinstatement of conditioned threat responses irrespective of shock intensity or reminder condition. Hence, regardless of the intensity of the threat memory, the reminder procedure was ineffective in preventing the return of threat responses in rats. We thus find no evidence that threat memory intensity is a potential modulator of the effectiveness of the reminder-extinction procedure.