Noradrenergic arousal and systems consolidation: maintaining memory specificity?

随着时间的推移，记忆被认为经历了神经重组，称为系统巩固，在此过程中，记忆至少部分从海马体转移到新皮层网络。这种系统整合是高度动态的，并且伴随着从详细的、特定的到更语义化的、类似要点的记忆的转换。系统整合是否可以被调节在很大程度上是未知的。情绪觉醒诱导的去甲肾上腺素是一种强大的初始记忆形成调节剂，通过增加杏仁核活动来增加记忆的强度和生动度，以及增强海马对记忆的参与。虽然去甲肾上腺素可以增强记忆的初始巩固，但其对系统巩固过程的影响以及记忆特异性的时间依赖性变化在很大程度上是未知的。基于最近的啮齿动物数据，我们假设编码后的去甲肾上腺素能刺激可能改变系统巩固过程并维持海马依赖和特异性的远程记忆。为了验证这一假设，健康的参与者将在编码一系列中性和情绪唤起的图片后，给予安慰剂或α - 2肾上腺素受体拮抗剂育亨宾，导致去甲肾上腺素能刺激增加。记忆将在编码后1天或28天进行识别测试。为了评估记忆的特异性，除了旧的和全新的项目外，识别测试将包括携带最初编码图片要点的诱饵，以及感知上相似的携带不同要点的诱饵。为了评估假设的系统巩固和编码后去甲肾上腺素能唤醒对记忆转化的神经基础，参与者将在编码和保留测试期间进行3T功能磁共振成像扫描。除了它们对我们理解人类记忆的重要意义，特别是对情绪记忆的长期生动性，这个项目的发现可能对异常情绪记忆处理突出的精神障碍有影响。

With time, memory is thought to undergo a neural reorganization, referred to as systems consolidation, during which memories are, at least partly, transferred from hippocampus to neocortical networks. This systems consolidation is highly dynamic and accompanied by a transformation from detailed, specific to more semantic, gist-like memory. Whether systems consolidation can be modulated is largely unknown. Emotional arousal-induced noradrenaline is known to be a powerful modulator of initial memory formation, leading via increased amygdala activity to increased memory strength and vividness as well as to enhanced hippocampal involvement in memory. Although it is well-established that noradrenaline may strengthen the initial consolidation of memory, its impact on systems consolidation processes and the time-dependent change in the specificity of memory is largely unknown. Based on recent rodent data, we hypothesize that post-encoding noradrenergic stimulation may change systems consolidation processes and maintain remote memories hippocampus dependent and specific. To test this hypothesis, healthy participants will be administered a placebo or the α2-adrenoceptor antagonist yohimbine, leading to increased noradrenergic stimulation, after they encode a series of neutral and emotionally arousing pictures. Memory will be tested in a recognition test, either 1 day or 28 days after encoding. To assess memory specificity, the recognition test will include, in addition to old and entirely novel items, lures carrying the gist of the initially encoded pictures as well as perceptually similar lures carrying a different gist. In order to assess the postulated systems consolidation and the neural underpinnings of post-encoding noradrenergic arousal on memory transformation, participants will be scanned with functional magnetic resonance imaging at 3T both during encoding and retention testing. Beyond their crucial relevance for our understanding of human memory in general and the long-term vividness of emotional memory in particular, the findings of this project might have implications for mental disorders in which aberrant emotional memory processing is prominent.