Department of Cognitive Neuroscience, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands.
Donders Institute for Brain, Cognition and Behaviour, Radboud University, 6525 EN Nijmegen, The Netherlands.
Proc Natl Acad Sci U S A. 2017 Aug 22;114(34):9176-9181. doi: 10.1073/pnas.1710819114. Epub 2017 Aug 8.
Emotional enhancement of memory by noradrenergic mechanisms is well-described, but the long-term consequences of such enhancement are poorly understood. Over time, memory traces are thought to undergo a neural reorganization, that is, a systems consolidation, during which they are, at least partly, transferred from the hippocampus to neocortical networks. This transfer is accompanied by a decrease in episodic detailedness. Here we investigated whether norepinephrine (NE) administration into the basolateral amygdala after training on an inhibitory avoidance discrimination task, comprising two distinct training contexts, alters systems consolidation dynamics to maintain episodic-like accuracy and hippocampus dependency of remote memory. At a 2-d retention test, both saline- and NE-treated rats accurately discriminated the training context in which they had received footshock. Hippocampal inactivation with muscimol before retention testing disrupted discrimination of the shock context in both treatment groups. At 28 d, saline-treated rats showed hippocampus-independent retrieval and lack of discrimination. In contrast, NE-treated rats continued to display accurate memory of the shock-context association. Hippocampal inactivation at this remote retention test blocked episodic-like accuracy and induced a general memory impairment. These findings suggest that the NE treatment altered systems consolidation dynamics by maintaining hippocampal involvement in the memory. This shift in systems consolidation was paralleled by time-regulated DNA methylation and transcriptional changes of memory-related genes, namely and ζ, in the hippocampus and neocortex. The findings provide evidence suggesting that consolidation of emotional memories by noradrenergic mechanisms alters systems consolidation dynamics and, as a consequence, influences the maintenance of long-term episodic-like accuracy of memory.
去甲肾上腺素能机制增强记忆的作用已得到充分描述,但这种增强的长期后果知之甚少。随着时间的推移,记忆痕迹被认为经历了神经重组,即系统巩固,在此过程中,它们至少部分地从海马体转移到新皮层网络。这种转移伴随着情景细节的减少。在这里,我们研究了在抑制性回避辨别任务(包括两个不同的训练环境)后,将去甲肾上腺素(NE)注入外侧杏仁核,是否会改变系统巩固的动态,以维持情景般的准确性和海马体对远距离记忆的依赖性。在 2 天的保留测试中,生理盐水和 NE 处理的大鼠都能准确地区分它们接受电击的训练环境。在保留测试前用 muscimol 对海马体进行失活,会破坏两组大鼠对电击环境的辨别。在 28 天时,生理盐水处理的大鼠表现出与海马体无关的检索和缺乏辨别能力。相比之下,NE 处理的大鼠继续表现出对电击环境关联的准确记忆。在这个远程保留测试中,海马体失活会阻止情景般的准确性,并导致一般的记忆损伤。这些发现表明,NE 治疗通过维持海马体在记忆中的参与来改变系统巩固的动态。这种系统巩固的转变与时间调节的 DNA 甲基化和记忆相关基因的转录变化相平行,即 和 ζ,在海马体和新皮层中。这些发现提供了证据,表明去甲肾上腺素能机制对情绪记忆的巩固改变了系统巩固的动态,并因此影响了长期情景般准确性的记忆维持。