Kida Satoshi
Nihon Shinkei Seishin Yakurigaku Zasshi. 2014 Nov;34(5-6):117-25.
Pavlovian fear conditioning is a model of fear learning and memory. The mechanisms regulating fear conditioning and memory have been investigated in humans and rodents. In this paradigm, animals learn and memorize an association between a conditioned stimulus (CS), such as context, and an unconditioned stimulus (US), such as an electrical footshock that induces fear. Fear memory generated though fear conditioning is stabilized via a memory consolidation process. Moreover, recent studies have shown the existence of memory processes that control fear memory following the retrieval of consolidated memory. Indeed, when fear memory is retrieved by re-exposure to the CS, the retrieved memory is re-stabilized via the reconsolidation process. On the other hand, the retrieval of fear memory by prolonged re-exposure to the CS also leads to fear memory extinction, new inhibitory learning against the fear memory, in which animals learn that they do not need to respond to the CS. Importantly, the reinforcement of fear memory after retrieval (i.e., re-experience such as flashbacks or nightmares) has been thought to be associated with the development of emotional disorders such as post-traumatic stress disorder (PTSD). In this review, I summarize recent progress in studies on the mechanism of fear conditioning and memory consolidation, reconsolidation and extinction, and furthermore, introduce our recent establishment of a mouse PTSD model that shows enhancement of fear memory after retrieval.
巴甫洛夫式恐惧条件反射是一种恐惧学习和记忆的模型。调节恐惧条件反射和记忆的机制已在人类和啮齿动物中得到研究。在这种范式中，动物学习并记住条件刺激（CS）（如环境）与非条件刺激（US）（如引起恐惧的足部电击）之间的关联。通过恐惧条件反射产生的恐惧记忆通过记忆巩固过程得以稳定。此外，最近的研究表明，在巩固记忆检索后存在控制恐惧记忆的记忆过程。事实上，当通过再次暴露于CS来检索恐惧记忆时，检索到的记忆通过重新巩固过程再次稳定下来。另一方面，长时间再次暴露于CS来检索恐惧记忆也会导致恐惧记忆消退，即对恐惧记忆产生新的抑制性学习，在此过程中动物学会它们无需对CS做出反应。重要的是，检索后恐惧记忆的强化（即如闪回或噩梦般的再次体验）被认为与创伤后应激障碍（PTSD）等情绪障碍的发展有关。在这篇综述中，我总结了关于恐惧条件反射和记忆巩固、重新巩固及消退机制研究的最新进展，此外，还介绍了我们最近建立的一种小鼠PTSD模型，该模型显示检索后恐惧记忆增强。
