ISSN 1671-3710
CN 11-4766/R

心理科学进展 ›› 2021, Vol. 29 ›› Issue (8): 1450-1461.doi: 10.3724/SP.J.1042.2021.01450

• 研究前沿 • 上一篇    下一篇



  1. 首都师范大学心理学院, 北京 100037
  • 收稿日期:2020-08-08 发布日期:2021-06-25
  • 通讯作者: 朱俊萍

How to overcome boundary conditions: Implications from the molecular mechanism of memory strength as a constraint on destabilization

ZHU Junping()   

  1. School of Psychology, Capital Normal University, Beijing 100037, China
  • Received:2020-08-08 Published:2021-06-25
  • Contact: ZHU Junping


长时记忆在激活后首先会变得不稳定(去稳定过程), 继而会经历一个再巩固过程重新稳定下来以维持记忆的关联性。在再巩固期间给予电击、药理或行为训练以干预记忆再巩固, 可以更改原有记忆的强度或内容。这有望成为临床上治疗病理性记忆的一种方法。然而, 一些边界条件(记忆痕迹强、时间久远等)导致记忆在简单激活后不能去稳定, 不会经历再巩固过程, 使干预再巩固的方法无法发挥作用。动物实验表明, 通过药理学地调控参与记忆去稳定的分子的活动以促进记忆去稳定, 可以成功克服边界条件。可见, 边界条件不是绝对的。未来研究可进一步探索更多、更优的促进记忆去稳定并克服边界条件的方法, 提升干预记忆再巩固疗法的临床应用潜能。

关键词: 记忆再巩固, 记忆去稳定, 边界条件, 泛素-蛋白酶体系统, 自噬


Retrieval of long-term memories can induce a destabilization process that returns them into a labile state, and then the labile state will be followed by a reconsolidation process that helps memories to restabilize and maintain their relevance. The reconsolidation process can be interfered by electroconvulsive shock, pharmacological treatment or behavioral training to update the original memories. Disrupting memory reconsolidation could become an approach tackling maladaptive memory. However, some boundary conditions such as training strength and memory age may prevent memory destabilization. Memory destabilization is the prerequisite for reconsolidation to occur. Therefore, they make reconsolidation-based interventions invalid. This may be taken as a potential stumbling block for reconsolidation-based interventions: in clinical practice, old and strong maladaptive memories are the norm rather than the exception. Therefore, overcoming the boundary conditions has become an urgent problem, and it is also one of the hotspots in the field of reconsolidation in recent years. It is because boundary conditions hinder the memory destabilization that memory can’t experience reconsolidation. Therefore, this paper first summarized and analyzed the molecules involved in memory destabilization and their respective roles in memory destabilization. Among the boundary conditions, memory strength is the most studied. Therefore, combining the molecules of memory destabilization and a series of experimental evidences about the effect of memory strength on memory reconsolidation, we inferred that the molecular path of memory strength hindering memory destabilization may be: as the memory strength increases, the noradrenergic projection from locus coeruleus to amygdala will be enhanced, and then the expression levels of NR2B and GluA2 in basolateral amygdala, the key molecules of memory destabilization, will be changed through this projection, and thus memory destabilization will be inhibited. Boundary conditions can affect the activities of key molecules involved in memory destabilization, thus hindering memory reconsolidation. This suggests that, in turn, pharmacological manipulation of the molecules involved in memory destabilization before memory activation can overcome the barrier of memory destabilization caused by the boundary conditions formed during memory coding. Previous animal experiments have shown that NMDAR, one of the key molecules involved in memory destabilization, was pharmacologically regulated before memory activation, which successfully promoted memory destabilization and overcome the boundary conditions. It can be seen that the boundary conditions are not absolute. All the molecules involved in memory destabilization are expected to be the target molecules to overcome the boundary conditions. The role of other molecules involved in memory destabilization, except NMDAR, in overcoming the boundary conditions is still unknown and needs to be further explored. The effect of these molecules in overcoming the boundary conditions may be different, and the clinical application potential is also different, which requires a lot of comparative experiments to select the best target molecules. Future research can further explore more and better methods to promote memory destabilization and overcome boundary conditions, and enhance the clinical application potential of reconsolidation-based interventions.

Key words: memory reconsolidation, memory destabilization, boundary conditions, ubiquitin - proteasome system, autophagy