Noradrenergic activation of the basolateral amygdala maintains hippocampus-dependent accuracy of remote memory
Noradrenergic activation of the basolateral amygdala maintains hippocampus-dependent accuracy of remote memory
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DOI：
10.1073/pnas.1710819114
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发表时间：
2017-08-22
影响因子：
11.1
通讯作者：
Roozendaal, Benno
中科院分区：
文献类型：
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作者：
Atucha, Erika;Vukojevic, Vanja;Roozendaal, Benno
去甲肾上腺素能机制对记忆的情绪增强已有充分描述，但对这种增强的长期后果却知之甚少。随着时间的推移，记忆痕迹被认为会经历神经重组，即系统整合，在此期间它们至少部分地从海马体转移到新皮质网络。这种转移伴随着情节细节的减少。在这里，我们研究了在抑制性回避辨别任务（包括两种不同的训练环境）训练后，将去甲肾上腺素（NE）注射到基底外侧杏仁核是否会改变系统整合动力学以维持情景式准确性和远程记忆的海马依赖性。在 2 d 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足部电击的训练环境。在保留测试之前用蝇蕈醇灭活海马破坏了两个治疗组对休克环境的辨别。 28 天时，生理盐水处理的大鼠表现出海马体独立检索和缺乏辨别能力。相比之下，接受 NE 治疗的大鼠继续表现出对电击环境关联的准确记忆。在这个远程记忆测试中，海马失活阻碍了情景式的准确性，并引起了普遍的记忆障碍。这些发现表明，NE 治疗通过维持海马参与记忆来改变系统巩固动力学。这种系统整合的转变与海马和新皮质中记忆相关基因（即 Reln 和 Pkm zeta）的时间调节 DNA 甲基化和转录变化并行。研究结果提供的证据表明，去甲肾上腺素能机制对情绪记忆的巩固会改变系统巩固动力学，从而影响记忆的长期情景准确性的维持。
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 Reln and Pkm zeta, 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.