Mineralocorticoid Receptor Blockade Prevents Stress-Induced Modulation of Multiple Memory Systems in the Human Brain
Mineralocorticoid Receptor Blockade Prevents Stress-Induced Modulation of Multiple Memory Systems in the Human Brain
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DOI：
10.1016/j.biopsych.2013.06.001
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发表时间：
2013-12-01
影响因子：
10.6
通讯作者：
Wolf, Oliver T.
中科院分区：
文献类型：
--
作者：
Schwabe, Lars;Tegenthoff, Martin;Wolf, Oliver T.
背景：越来越多的证据表明，压力可能会协调大脑中多个记忆系统的参与。特别是，压力被认为有利于背侧纹状体依赖的程序性记忆，而不是背侧纹状体依赖的陈述性记忆。然而，神经内分泌机制的调节作用的压力仍然难以捉摸，特别是在人类。在这里，我们使用事件相关功能磁共振成像和MR的药理学阻断相结合的方法，靶向盐皮质激素受体（MR）在人脑背侧纹状体和海马记忆系统的应激诱导调制中的作用。80名健康受试者接受MR拮抗剂螺内酯（300 mg）或安慰剂，并在他们进行之前接受应激或控制操作，结果：安慰剂后的压力不影响学习成绩，但减少了外显任务知识，并导致更多的程序性学习策略的使用相对增加。在神经水平上，压力促进了以纹状体为基础的学习，而牺牲了以纹状体为基础的学习。功能连接分析表明，这种转变与杏仁核与海马和背侧纹状体的耦合改变有关。在应激前阻断盐皮质激素受体可以防止应激诱导的背侧纹状体程序性学习的转变，这与应激诱导的杏仁核与海马和背侧纹状体连接的改变相同，但会导致显著受损的表现。我们的研究结果表明，应激诱导的从海马到背侧纹状体记忆系统的转变是由杏仁核介导的，杏仁核是在应激后保持表现所必需的，并且依赖于MR。
Background: Accumulating evidence suggests that stress may orchestrate the engagement of multiple memory systems in the brain. In particular, stress is thought to favor dorsal striatum-dependent procedural over hippocampus-dependent declarative memory. However, the neuroendocrine mechanisms underlying these modulatory effects of stress remain elusive, especially in humans. Here, we targeted the role of the mineralocorticoid receptor (MR) in the stress-induced modulation of dorsal striatal and hippocampal memory systems in the human brain using a combination of event-related functional magnetic resonance imaging and pharmacologic blockade of the MR.Methods: Eighty healthy participants received the MR antagonist spironolactone (300 mg) or a placebo and underwent a stressor or control manipulation before they performed, in the scanner, a classification task that can be supported by the hippocampus and the dorsal striatum.Results: Stress after placebo did not affect learning performance but reduced explicit task knowledge and led to a relative increase in the use of more procedural learning strategies. At the neural level, stress promoted striatum-based learning at the expense of hippocampus-based learning. Functional connectivity analyses showed that this shift was associated with altered coupling of the amygdala with the hippocampus and dorsal striatum. Mineralocorticoid receptor blockade before stress prevented the stress-induced shift toward dorsal striatal procedural learning, same as the stress-induced alterations of amygdala connectivity with hippocampus and dorsal striatum, but resulted in significantly impaired performance.Conclusions: Our findings indicate that the stress-induced shift from hippocampal to dorsal striatal memory systems is mediated by the amygdala, required to preserve performance after stress, and dependent on the MR.