Fear extinction allows for adaptive control of learned fear responses but often fails, resulting in a renewal or spontaneous recovery of the extinguished fear, i.e., forgetting of the extinction memory readily occurs. Using an activity-dependent neuronal labeling strategy, we demonstrate that engram neurons for fear extinction memory are dynamically positioned in the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and ventral hippocampus (vHPC), which constitute an engram construct in the term of directional engram synaptic connectivity from the BLA or vHPC to mPFC, but not that in the opposite direction, for retrieval of extinction memory. Fear renewal or spontaneous recovery switches the extinction engram construct from an accessible to inaccessible state, whereas additional extinction learning or optogenetic induction of long-term potentiation restores the directional engram connectivity and prevents the return of fear. Thus, the plasticity of engram construct underlies forgetting of extinction memory.

恐惧消退允许对习得的恐惧反应进行适应性控制，但经常会失败，从而导致消失的恐惧的更新或自发恢复，即很容易忘记消退记忆。使用活动依赖性神经元标记策略，我们证明恐惧消退记忆的印迹神经元动态定位在内侧前额叶皮层 (mPFC)、基底外侧杏仁核 (BLA) 和腹侧海马体 (vHPC) 中，它们构成了大脑中的印迹构造从 BLA 或 vHPC 到 mPFC 的定向印迹突触连接的术语，但不是相反的方向，用于检索消退记忆。恐惧更新或自发恢复将消退印迹结构从可访问状态切换到不可访问状态，而额外的消退学习或长期增强的光遗传学诱导可恢复定向印迹连接并防止恐惧回归。因此，印迹构造的可塑性是消退记忆遗忘的基础。