Abstract:

Recent studies of fear memories conducted in both humans and animals have suggested that new fear memories (1-day old) can be attenuated using a reconsolidation update mechanism, which is selective to the reactivated cue. In real life, patients with post-traumatic stress disorder (PTSD) usually receive treatment much after the traumatic memories form, and a traumatic event can be associated with multiple cues. However, the cue specificity of reconsolidation update mechanism in remote fear memories (> 7 days) remains largely unknown.
To assess the cue specificity of remote fear memories (14 days) reconsolidation, we explored whether retrieval-extinction during the reconsolidation time window of remote fear memories is selective to the reactivated cue. We used a within-subject design, and skin-conductance response (SCR) served as the measurement. All subjects underwent fear conditioning by three coloured squares on day 1. Two squares (CSa+ and CSb+) were paired with the shock on 38% of the trials. The third square (CS-) was never paired with the shock. Fourteen days later, subjects received a single presentation of CSa+ (reactivated CS+) but not CSb+ (non-reactivated CS+). Ten minutes after the reminder trial, extinction training was conducted (within the reconsolidation window). Twenty-four hours later, all subjects returned to the experiment room and received spontaneous recovery test of the remote fear memories.
Results showed that there is no recovery for the reminded CS+, but significant recovery for non-reminded CS+ during spontaneous recovery testing. The recovery index (which was calculated as the first trial on day 16 minus the last trial on day 15 by differential SCR) of non-reminded CS+ was found to be significantly higher than that of the reminded CS+ (p < 0.05). Thus, retrieval-extinction during reconsolidation window only attenuates the fear memory of the reactivated cue.
Our findings demonstrated that the reconsolidation update mechanism is effective for attenuating remote fear memories, and that this mechanism is selective to the reactivated cue of remote memories. We provide evidence to support the ongoing efforts in the development of novel strategies to combat remote pathogenic memories, which we think could lead to a more effective application of the reconsolidation update mechanism.

Key words: remote memory reconsolidation, cue specificity, conditioned fear, retrieval-extinction