Contribution of AMPA and NMDA receptors to early and late phases of LTP in hippocampal slices

Contribution of AMPA and NMDA receptors to early and late phases of LTP in hippocampal slices
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DOI:
10.1016/j.neures.2006.03.001
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发表时间:
2006-06-01
影响因子:
2.9
通讯作者:
Wigstrom, Holger
Wigstrom, Holger
中科院分区:
医学4区
文献类型:
--
作者:
Dozmorov, Mikhail;Li, Rui;Wigstrom, Holger

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在大鼠海马脑片上观察了长时程增强(LTP)表达4 h时α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)和N-甲基-D-天冬氨酸(NMDA)受体介导的反应。使用含有NMDA受体拮抗剂AP 5和低浓度Mg 2+的改良培养基来监测分离的AMPA反应。NMDA成分测定从复合兴奋性突触后电位(EPSP)下短暂(15-20分钟)冲洗出的AP 5。UP在低浓度AP 5的培养基中诱导,导致AMPA组分比NMDA组分在诱导后1 h和4 h增加约2倍。如果在“正常Mg 2+”中诱导UP,并且在实验结束时从复合或分离的NMDA EPSP(有或没有GABA能抑制的阻断)评估NMDA组分,则获得类似的结果。一般认为,LTP在最初的几个小时内经历生物化学和/或结构转化。然而,我们的研究表明,在此期间,LTP的恒定表达,至少在AMPA与NMDA组分方面。数据支持的概念,LTP启动作为一个主要的AMPA受体的扩增,并保持至少4小时。(c)2006年Elsevier爱尔兰有限公司和日本神经科学学会。All rights reserved.
Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor mediated responses were investigated in rat hippocampal slices under 4 h of long-term potentiation (LTP) expression. A modified medium containing the NMDA receptor antagonist AP5 and low concentration of Mg2+ was used to monitor isolated AMPA responses. NMDA components were determined from composite excitatory postsynaptic potentials (EPSPs) under brief (15-20 min) wash-out of AP5. UP was induced in a medium with low concentration of AP5, resulting in an about two-fold larger increase of the AMPA component than of the NMDA component at both I h and 4 h after induction. Similar results were obtained if UP was induced in "normal Mg2+" and the NMDA components were assessed at the end of experiment, from either composite or isolated NMDA EPSPs, with or without blockade of GABAergic inhibition. It is generally believed that LTP undergoes biochemical and/or structural conversions during the first few hours. Our study, however, shows constant expression of LTP, at least in terms of AMPA versus NMDA components, during this time. The data support the notion that LTP initiates as a predominant amplification of AMPA receptors and remains so for at least 4 h. (c) 2006 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.