Reconsolidation of Emotional Memory in Humans

描述（由申请人提供）：详细的动物研究提供了强有力的证据，表明情绪记忆在每次提取后都会被重新巩固，蛋白质合成抑制剂或β -肾上腺素能拮抗剂会损害这一过程（例如，Nadar等人，2000；Debiec和Ledoux， 2004）。人们认为，一旦记忆经过了不稳定的形成状态，就会变得稳定，而这一基本发现表明，可能有机会破坏旧的情感记忆，更重要的是，破坏创伤性记忆。然而，到目前为止，还没有证据表明人类存在这样的过程。当前提出的研究目的是寻找人类情绪记忆重新巩固的证据，并阐明其潜在的大脑机制。我们的策略将是在正常健康的人类志愿者中使用与动物实验相同的程序来检查再巩固。这些程序将旨在检测杏仁核和海马体的特定贡献，这两个大脑区域与焦虑和情绪障碍有关，对再巩固过程。具体来说，我们将尝试通过检查-肾上腺素能阻滞剂普萘洛尔对恐惧条件反射及其情境调节的影响，为人类杏仁核和海马依赖性记忆的重新巩固提供第一个证据。有两个具体目标：具体目标1:a)我们将研究β -肾上腺素能受体阻断对人类杏仁核依赖性记忆再巩固的影响，使用线索恐惧条件反射范式；b)我们将研究β -肾上腺素能阻断效应对杏仁核依赖性记忆再巩固影响的神经机制。具体目标2:a)我们将使用情境介导的恐惧恢复范式，研究β -肾上腺素能受体阻断对人类海马体依赖性记忆再巩固的影响；b)我们将研究β -肾上腺素能阻断效应对海马体依赖性记忆再巩固改变的神经机制。

DESCRIPTION (provided by applicant): Detailed animal studies provide strong evidence that emotional memories are reconsolidated each time after retrieval, and that protein synthesis inhibitors or beta-adrenergic antagonists can impair this process (e.g., Nadar et al., 2000; Debiec and Ledoux, 2004). In contrast to the notion that memories are stable once they have passed the labile state of formation to being fully consolidated, this basic finding suggests there might be a window of opportunity to impair old emotional memories, and more importantly, traumatic memories. However, to date, there is no evidence that such a process exists in humans. The aim of the current proposed research is to find evidence for reconsolidation of emotional memory in humans, and to elucidate its underlying brain mechanisms. Our strategy will be to examine reconsolidation in normal healthy human volunteers, using procedures that mirror those used in animals. These procedures will be aimed at detecting specific contributions of the amygdala and the hippocampus, two brain regions implicated in anxiety and emotional disorders, to reconsolidation processes. Specifically, we would attempt to provide the first evidence for reconsolidation of human amygdala and hippocampal dependent memories by examining the effects of the beta-adrenergic blocker propranolol on fear conditioning and its contextual modulation. There are two specific aims: Specific Aim 1: a) We will examine the effects of beta-adrenergic receptor blockade on reconsolidation of amygdala-dependent memories in humans, using a cue fear-conditioning paradigm; b) We will investigate the neural mechanisms underlying alterations in re-retrieval of amygdala-dependent memories induced by beta-adrenergic blockade effects on reconsolidation. Specific Aim 2: a) We will examine the effects of beta-adrenergic receptor blockade on reconsolidation of hippocampal-dependent memories in humans, using a context-mediated fear reinstatement paradigm; b) We will investigate the neural mechanisms underlying alterations in re-retrieval of hippocampal-dependent memories induced by beta-adrenergic blockade effects on reconsolidation.