条件性恐惧记忆再巩固的神经分子机制研究

<正>创伤后应激障碍(post-traumatic stress disorder,PTSD)是经历强烈创伤性事件的个体再次暴露在相似创伤情境时出现以恐惧记忆重复体验为核心症状的反应性精神障碍~([1])。正常的恐惧记忆和恐惧反应是人和动物重要的生存活动,可以帮助机体启动防御机制。然而对于PTSD患者来说,这种恐惧记忆引起的恐惧反应被某些神经生理机制扩大并长期巩固,对患者造成了严重的身心伤害。近年来随着恐     

Rapid eye movement sleep deprivation does not affect fear memory reconsolidation in rats

There is increasing evidence that sleep may be involved in memory consolidation. However, there remain comparatively few studies that have explored the relationship between sleep and memory reconsolidation. At present study, we tested the effects of rapid eye movement sleep deprivation (RSD) on the reconsolidation of cued (experiment 1) and contextual (experiment 2) fear memory in rats. Behaviour procedure involved four training phases: habituation, fear conditioning, reactivation and test. Rats were subjected to 6 h RSD starting either immediately after reactivation or 6 h later. The control rats were returned to their home cages immediately after reactivation and left undisturbed. Contrary to those hypotheses speculating a potential role of sleep in reconsolidation, we found that post-reactivation RSD whether from 0 to 6 h or 6 to 12 h had no effect on the reconsolidation of both cued and contextual fear memory. However, our present results did not exclude the potential roles of non-rapid eye movement sleep in the reconsolidation of fear memory or sleep in the reconsolidation of other memory paradigms.     

Nicotine enhances contextual fear memory reconsolidation in rats

There is increasing evidence that nicotine is involved in learning and memory. However, there remains no study that has explored the relationship between nicotine and memory reconsolidation. At present study, we tested the effects of nicotine on the reconsolidation of contextual fear memory in rats. Behavior procedure involved four training phases: habituation (Day 0), fear conditioning (Day 1), reactivation (Day 2) and test (Day 3). Rats were injected saline or nicotine (0.25, 0.5 and 1.0mg/kg) immediately after reactivation. Percent of time spent freezing was used to measure conditioned fear response. Results showed that compared with saline rats, rats with nicotine at 1.0mg/kg presented a significant increase of freezing response on Day 3. Nicotine at 1.0mg/kg was ineffective when injected 6h after reactivation. Further results showed that the enhancement of freezing response induced by nicotine at 1.0mg/kg was dependent on fear memory reconsolidation, and was not attributed to an enhancement of the nonspecific freezing response 24h after nicotine administration. The results suggest that nicotine administration immediately after reactivation enhances contextual fear memory reconsolidation. Our present finding extends previous research on the nicotinic effects on learning and memory.     

The roles of RNA synthesis and protein translation during reconsolidation of passive-avoidance learning in the day-old chick

This series of experiments investigated the role of protein translation and RNA synthesis on consolidation and reconsolidation of passive avoidance learning (PAL) in day-old chicks. Although it is well established that protein translation is required after a reminder, there are conflicting reports in the literature concerning the requirement for RNA synthesis at this time. Day-old male New Hampshire × White Leghorn chicks were trained on a single trial passive avoidance task. The results confirmed the requirement for protein translation during reconsolidation with memory deficits induced by anisomycin (ANI) (10 mg/kg) detected at 60 min post-reminder. It was also established that RNA synthesis was required for consolidation of PAL through inhibition by 5,6-Dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) (0.075 µg/kg), administered at or after training. The same dose of DRB was also found to inhibit memory post-reactivation. However injections were required before the reminder trial and memory deficits were evident by 60 min, consistent with that found for ANI post-reminder. As with ANI, the DRB-induced memory deficit post-reminder was also transient, and resolved by 24 h post-reminder. For both reconsolidation drug studies, the memory deficit was wholly dependent on the memory being reactivated by a reminder-trial. The study highlights an important role for RNA synthesis following memory reactivation.     

Ouabain does not impair reconsolidation following a reminder of passive avoidance learning in the day-old chick

This study investigated the effect of ouabain, an inhibitor of NA⁺ and K⁺ ATPase, on consolidation and reconsolidation of a passive avoidance learning task in the day-old chick. In the consolidating trace, ouabain is thought to inhibit an intermediate-term memory phase, some aspects of which acts as a “trigger” for long-term stabilisation of the trace by new protein synthesis. It was hypothesised that a similar process may initiate the protein synthesis observed following reminder-activated reconsolidation in the young chick. Chicks were trained on a single trial passive avoidance task. A dose of 0.2 ug/kg ouabain was administered intracranially either 5 min post-training (consolidation processes) or 5 min post-reminder (reconsolidation processes). Consistent with previous research, ouabain administration induced a memory deficit following the initial learning trial. However, contrary to expectation, ouabain did not disrupt memory processing post-reactivation. This finding provides further evidence for the notion that consolidation and reconsolidation are associated with similar, but distinct, stages of processing.     

Reconsolidation in a human fear conditioning study: A test of extinction as updating mechanism

Disrupting reconsolidation seems to be a promising approach to dampen the expression of fear memory. Recently, we demonstrated that disrupting reconsolidation by a pharmacological manipulation specifically targeted the emotional expression of memory (i.e., startle response). Here we test in a human differential fear-conditioning paradigm with fear-relevant stimuli whether the spacing of a single unreinforced retrieval trial relative to extinction learning allows for “rewriting” the original fear association, thereby preventing the return of fear. In contrast to previous findings reported by Schiller et al. (2010), who used a single-method for indexing fear (skin conductance response) and fear-irrelevant stimuli, we found that extinction learning within the reconsolidation window did not prevent the recovery of fear on multiple indices of conditioned responding (startle response, skin conductance response and US-expectancy). These conflicting results ask for further critical testing given the potential impact on the field of emotional memory and its application to clinical practice.