Long-Lasting Increase of Corticosterone After Fear Memory Reactivation: Anxiolytic Effects and Network Activity Modulation in the Ventral Hippocampus
Long-Lasting Increase of Corticosterone After Fear Memory Reactivation: Anxiolytic Effects and Network Activity Modulation in the Ventral Hippocampus
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DOI：
10.1038/npp.2012.192
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发表时间：
2013-02-01
影响因子：
7.6
通讯作者：
Stork, Oliver
中科院分区：
文献类型：
--
作者：
Albrecht, Anne;Caliskan, Gursel;Stork, Oliver
病理性恐惧和焦虑可以在啮齿动物中进行研究，通过恐惧条件反射和暴露于提醒线索。这些范例被认为是关键涉及腹侧海马，这也是糖皮质激素在大脑中作用的关键部位。在这里，我们证明了一个持久的减少红藻氨酸诱导的γ振荡片制备的腹侧海马区CA 3，30天后，一个单一的恐惧条件训练。减少γ功率是敏感的皮质酮的应用和减少糖皮质激素和盐皮质激素受体mRNA表达的腹侧海马CA 3层。恐惧再激活会议24小时后，初始条件反射正常化受体表达水平和衰减皮质酮介导的恢复γ振荡。此外，它增加了基线和刺激诱导的皮质酮血浆水平，并诱发了恐惧记忆的泛化背景。在高架十字迷宫中，恐惧再激活和非再激活小鼠腹侧海马γ振荡的减少与焦虑样行为的减少有关。利用皮质酮的昼夜节律波动，我们证明了早上高内源性基础皮质酮血浆浓度与恐惧再激活小鼠焦虑样行为减少的相关性。通过腹侧海马的局部应用验证了该激素的抗焦虑作用。我们的数据表明，皮质酮作用于腹侧海马网络活动具有抗焦虑作用后，恐惧暴露，突出其潜在的治疗价值焦虑症。Neuropsychopharmacology（2013）38，386-394; doi：10.1038/npp.2012.192; 2012年9月12日在线发表
Pathological fear and anxiety can be studied, in rodents, with fear conditioning and exposure to reminder cues. These paradigms are thought to critically involve the ventral hippocampus, which also serves as key site of glucocorticoid action in the brain. Here, we demonstrate a long-lasting reduction of kainate-induced gamma oscillations in slice preparations of the ventral hippocampal area CA3, 30 days after a single fear conditioning training. Reduction of gamma power was sensitive to corticosterone application and associated with a decrease in glucocorticoid and mineralocorticoid receptor mRNA expression across strata of the ventral hippocampal CA3. A fear reactivation session 24 h after the initial conditioning normalized receptor expression levels and attenuated the corticosterone-mediated recovery of gamma oscillations. It moreover increased both baseline and stimulus-induced corticosterone plasma levels and evoked a generalization of fear memory to the background context. Reduced ventral hippocampal gamma oscillation in both fear reactivated and non-reactivated mice were associated with a decrease of anxiety-like behavior in an elevated plus maze. Taking advantage of the circadian fluctuation in corticosterone, we demonstrated the association of high endogenous basal corticosterone plasma concentrations during morning hours with reduced anxiety-like behavior in fear reactivated mice. The anxiolytic effect of the hormone was verified with local applications to the ventral hippocampus. Our data suggest that corticosterone acting on ventral hippocampal network activity has anxiolytic-like effects following fear exposure, highlighting its potential therapeutic value for anxiety disorders. Neuropsychopharmacology (2013) 38, 386-394; doi:10.1038/npp.2012.192; published online 12 September 2012