Translational Approaches Targeting Reconsolidation.
Translational Approaches Targeting Reconsolidation.
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DOI：
10.1007/7854_2015_5008
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发表时间：
2016
影响因子：
--
通讯作者：
Phelps EA
中科院分区：
文献类型：
--
作者：
Kroes MC;Schiller D;LeDoux JE;Phelps EA
适应不良的学习反应和记忆导致精神障碍，构成重大的社会经济负担。主要的治疗方法教导患者抑制适应不良反应，但并没有摆脱记忆本身，这解释了为什么许多患者即使在最初成功治疗后也会出现症状复发。这突出表明，需要发现更持久和强大的技术，以减少适应不良的学习行为。一种潜在的有希望的方法是通过靶向记忆再巩固来改变原始记忆，而不是抑制它。最近的研究表明，重新激活旧的记忆会导致一段时间的记忆灵活性，需要重新存储或重新巩固记忆才能持久。这个重新整合期允许一个窗口来修改特定的旧内存。记忆灵活性在重新激活后的更新具有巨大的临床潜力，因为它能够靶向重新巩固和改变导致适应不良的精神状态和行为的特定学习反应和记忆。在这里，我们将审查非人类动物，健康的人类受试者和临床人群的转化研究，旨在通过生物治疗（电刺激，去甲肾上腺素能拮抗剂）或行为干预（再激活-消退范式）靶向再巩固来改变记忆。这两种方法都已成功地用于修改厌恶和食欲记忆，但在治疗临床人群的有效性有限。我们将讨论记忆的灵活性取决于测试的记忆类型和特定类型记忆的大脑区域。此外，我们何时以及如何才能最有效地重新激活记忆并诱导灵活性在很大程度上是不清楚的。最后，开发能够靶向再巩固并安全用于人类的药物将优化跨物种翻译。增加对重新激活后记忆灵活性的机制和局限性的了解应该有助于优化精神病患者的治疗效果。
Maladaptive learned responses and memories contribute to psychiatric disorders that constitute a significant socio-economic burden. Primary treatment methods teach patients to inhibit maladaptive responses, but do not get rid of the memory itself, which explains why many patients experience a return of symptoms even after initially successful treatment. This highlights the need to discover more persistent and robust techniques to diminish maladaptive learned behaviours. One potentially promising approach is to alter the original memory, as opposed to inhibiting it, by targeting memory reconsolidation. Recent research shows that reactivating an old memory results in a period of memory flexibility and requires restorage, or reconsolidation, for the memory to persist. This reconsolidation period allows a window for modification of a specific old memory. Renewal of memory flexibility following reactivation holds great clinical potential as it enables targeting reconsolidation and changing of specific learned responses and memories that contribute to maladaptive mental states and behaviours. Here, we will review translational research on non-human animals, healthy human subjects, and clinical populations aimed at altering memories by targeting reconsolidation using biological treatments (electrical stimulation, noradrenergic antagonists) or behavioural interference (reactivation–extinction paradigm). Both approaches have been used successfully to modify aversive and appetitive memories, yet effectiveness in treating clinical populations has been limited. We will discuss that memory flexibility depends on the type of memory tested and the brain regions that underlie specific types of memory. Further, when and how we can most effectively reactivate a memory and induce flexibility is largely unclear. Finally, the development of drugs that can target reconsolidation and are safe for use in humans would optimize cross-species translations. Increasing the understanding of the mechanism and limitations of memory flexibility upon reactivation should help optimize efficacy of treatments for psychiatric patients.