Department of Psychology, University of Cambridge , Cambridge CB2 3EB, United Kingdom.
eNeuro. 2015 Mar 6;2(1). doi: 10.1523/ENEURO.0024-14.2015. eCollection 2015 Jan-Feb.
Disrupting maladaptive memories may provide a novel form of treatment for neuropsychiatric disorders, but little is known about the neurochemical mechanisms underlying the induction of lability, or destabilization, of a retrieved consolidated memory. Destabilization has been theoretically linked to the violation of expectations during memory retrieval, which, in turn, has been suggested to correlate with prediction error (PE). It is well-established that PE correlates with dopaminergic signaling in limbic forebrain structures that are critical for emotional learning. The basolateral amygdala is a key neural substrate for the reconsolidation of pavlovian reward-related memories, but the involvement of dopaminergic mechanisms in inducing lability of amygdala-dependent memories has not been investigated. Therefore, we tested the hypothesis that dopaminergic signaling within the basolateral amygdala is required for the destabilization of appetitive pavlovian memories by investigating the effects dopaminergic and protein synthesis manipulations on appetitive memory reconsolidation in rats. Intra-amygdala administration of either the D1-selective dopamine receptor antagonist SCH23390 or the D2-selective dopamine receptor antagonist raclopride prevented memory destabilization at retrieval, thereby protecting the memory from the effects of an amnestic agent, the protein synthesis inhibitor anisomycin. These data show that dopaminergic transmission within the basolateral amygdala is required for memory labilization during appetitive memory reconsolidation.
破坏适应不良的记忆可能为神经精神疾病提供一种新的治疗形式，但对于引发检索到的已巩固记忆的不稳定性或不稳定性的神经化学机制知之甚少。不稳定性在理论上与记忆检索过程中的期望违反有关，而这反过来又与预测误差 (PE) 有关。众所周知，PE 与边缘前脑结构中的多巴胺能信号相关，这些结构对于情绪学习至关重要。外侧杏仁核是条件性奖赏记忆再巩固的关键神经基质，但多巴胺能机制在诱导杏仁核依赖性记忆不稳定性中的作用尚未得到研究。因此，我们通过研究多巴胺能和蛋白质合成操作对大鼠的奖赏性条件性记忆再巩固的影响，测试了外侧杏仁核内多巴胺能信号在奖赏性条件性记忆不稳定性中的作用的假设。内侧杏仁核内给予 D1 选择性多巴胺受体拮抗剂 SCH23390 或 D2 选择性多巴胺受体拮抗剂 raclopride 可在检索时防止记忆不稳定，从而保护记忆免受遗忘剂、蛋白质合成抑制剂 anisomycin 的影响。这些数据表明，在奖赏性记忆再巩固过程中，外侧杏仁核内的多巴胺能传递对于记忆不稳定是必需的。
