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，证明情感记忆在每次提取后都会重新巩固，并且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年; Debiec和Ledoux，2004年）。与记忆一旦经过不稳定的形成状态而完全巩固就稳定的概念相反，这一基本发现表明，可能存在一个机会之窗来损害旧的情感记忆，更重要的是，创伤记忆。然而，到目前为止，没有证据表明这种过程存在于人类中。目前提出的研究的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。我们的策略是在正常健康的人类志愿者中检查再巩固，使用反映动物中使用的程序。这些程序旨在检测杏仁核和海马体这两个与焦虑和情绪障碍有关的大脑区域对重新巩固过程的具体贡献。具体来说，我们将试图提供第一个证据，重新巩固人类杏仁核和海马依赖的记忆，通过检查β-肾上腺素能受体阻滞剂普萘洛尔对恐惧条件反射及其上下文调制的影响。有两个具体目标：具体目标1：a）我们将使用线索恐惧-条件化范式，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; B）我们将研究由β-肾上腺素能受体阻断对再巩固的影响诱导的杏仁核依赖性记忆再提取改变的神经机制。具体目标二：a）我们将使用情境介导的恐惧恢复范例来检查β-肾上腺素能受体阻断对人类的海马依赖性记忆的再巩固的影响; B）我们将研究由β-肾上腺素能受体阻断对再巩固的影响诱导的海马依赖性记忆的再提取的潜在改变的神经机制。

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.