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AMPA和NMDA受体对海马切片中长时程增强早期和晚期阶段的作用。

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

作者信息

Dozmorov Mikhail, Li Rui, Abbas Abdul-Karim, Hellberg Fredrik, Farre Cecilia, Huang Fen-Sheng, Jilderos Barbro, Wigström Holger

机构信息

Department of Medical Biophysics, Institute of Neuroscience and Physiology, Göteborg University, Box 433, 405 30 Göteborg, Sweden.

出版信息

Neurosci Res. 2006 Jun;55(2):182-8. doi: 10.1016/j.neures.2006.03.001. Epub 2006 May 5.

DOI:10.1016/j.neures.2006.03.001
PMID:16678928
Abstract

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 4h of long-term potentiation (LTP) expression. A modified medium containing the NMDA receptor antagonist AP5 and low concentration of Mg(2+) 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. LTP 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 1h and 4h after induction. Similar results were obtained if LTP was induced in "normal Mg(2+)" 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 4h.

摘要

在大鼠海马切片中,研究了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,该反应处于4小时的长时程增强(LTP)表达状态下。使用含有NMDA受体拮抗剂AP5和低浓度镁离子(Mg²⁺)的改良培养基来监测分离的AMPA反应。在短暂(15 - 20分钟)洗脱AP5的情况下,从复合兴奋性突触后电位(EPSP)中测定NMDA成分。在含有低浓度AP5的培养基中诱导LTP,结果在诱导后1小时和4小时,AMPA成分的增加幅度比NMDA成分大约大两倍。如果在“正常镁离子(Mg²⁺)”条件下诱导LTP,并在实验结束时从复合或分离的NMDA EPSP中评估NMDA成分,无论是否阻断GABA能抑制,都能得到类似结果。一般认为LTP在最初几个小时内会经历生化和/或结构转变。然而,我们的研究表明,在此期间LTP至少在AMPA与NMDA成分方面保持恒定表达。这些数据支持了这样一种观点,即LTP最初是作为AMPA受体的主要放大作用开始的,并且至少持续4小时。

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