Hippocampal long-term depression mediates spatial reversal learning in the Morris water maze
Hippocampal long-term depression mediates spatial reversal learning in the Morris water maze
复制标题
海马长期抑郁介导莫里斯水迷宫的空间逆转学习
DOI：
10.1016/j.neuropharm.2012.06.027
复制
发表时间：
2013-01-01
影响因子：
4.7
通讯作者：
Wang, Yu Tian
中科院分区：
文献类型：
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作者：
Dong, Zhifang;Bai, Yanrui;Wang, Yu Tian
海马兴奋性突触的可塑性被认为是空间学习记忆的细胞机制。然而，大多数以前的研究都集中在长时程增强（LIP）在学习和记忆中的作用，而对长时程抑郁（LTD）的作用知之甚少。在这里，我们报告，在Morris水迷宫中的海马依赖的空间学习促进海马CM LTD在体内的诱导。LTD可通过全身应用选择性GluN 2B拮抗剂Ro 25 -6981（6 mg/kg，i. p.）或合成肽Tat-GluA 2（3 γ）（3 μ mol/kg，i. p.）干扰AMPA受体的内吞作用。此外，这两种机制和结构不同的抑制剂的全身或海马内给药损害了新的目标位置的空间反转学习，当隐藏的平台被移动到与初始目标位置相对的象限时。值得注意的是，急性升高的平台应激，这有利于海马LTD诱导，增强了空间反转记忆的获取和检索。目前的研究表明，逆转学习是通过阻断海马LTD受损，并通过促进海马LTD增强，这表明海马LTD可能是必要的和足够的调解新的信息processing.This文章的一部分，题为“认知增强剂”的特刊。(C)2012爱思唯尔有限公司保留所有权利。
Synaptic plasticity at hippocampal excitatory synapses has been proposed as the cellular mechanism underlying spatial learning and memory. However, most previous studies have focused on the role of long-term potentiation (LIP) in learning and memory, and much less is known about the role of long-term depression (LTD). Here, we report that hippocampal-dependent spatial learning in the Morris water maze facilitated hippocampal CM LTD induction in vivo. The LTD can be blocked by systemic application of the selective GluN2B antagonist Ro25-6981 (6 mg/kg, i.p.) or a synthetic peptide Tat-GluA2(3 gamma) (3 mu mol/kg, i.p.) that interferes with the endocytosis of AMPA receptors. In addition, systemic or intrahippocampal administration of these two mechanistically and structurally distinct inhibitors impaired spatial reversal learning of a novel target location, when the hidden platform was moved to the quadrant opposite the initial target location. Notably, acute elevated-platform stress, which facilitates hippocampal LTD induction, enhanced both acquisition and retrieval of spatial reversal memory. The present study demonstrates that reversal learning is impaired by blocking hippocampal LTD, and enhanced by facilitating hippocampal LTD, suggesting that hippocampal LTD may be necessary and sufficient to mediate new information processing.This article is part of a Special Issue entitled 'Cognitive Enhancers'. (C) 2012 Elsevier Ltd. All rights reserved.