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在体外实验中,阻断NMDA受体可揭示大鼠前额叶神经元突触效能的长期抑制。

Blockade of NMDA receptors unmasks a long-term depression in synaptic efficacy in rat prefrontal neurons in vitro.

作者信息

Hirsch J C, Crepel F

机构信息

CNRS-URA 1121, Laboratoire de Neurobiologie et Neuropharmacologie du Développement, Université Paris-Sud, Orsay, France.

出版信息

Exp Brain Res. 1991;85(3):621-4. doi: 10.1007/BF00231747.

DOI:10.1007/BF00231747
PMID:1680738
Abstract

All the experiments were carried out in slices of rat prefrontal cortex maintained in vitro. The effect of 2-amino-5-phosphonovalerate (APV) was tested on the postsynaptic potential (PSP) recorded in layer V pyramidal cells, in response to single or high frequency stimulation of the superficial layers I-II. Wash-out of Mg2+ increased the amplitude and duration of the PSPs. This effect resulted from activation of N-methyl-D-aspartate (NMDA) receptors since it was suppressed by bath application of APV. Furthermore, in every cell tested in Mg2+ containing medium (N = 16), exposure to APV reversibly reduced both mono- and polysynaptic components of the PSPs, indicating that, even in the control solution, activation of NMDA-coupled channels contributed to these synaptic events. Finally, the anomalous voltage-dependence of the EPSP in the presence of Mg2+ and its sensitivity to APV suggests that at least a fraction of the NMDA receptors are postsynaptically located. Tetanization was applied to the afferents of cells bathed in control- or APV-medium. Long-term potentiation (LTP) or long-term depression (LTD) is defined as an increase or a decrease respectively, of the PSPs peak amplitude or initial slope, lasting 20 min. In the control medium, LTP in synaptic efficacy was observed in 34% of the cells and LTD in 48% (N = 23). When exposed to APV, none of the cells tested (N = 16) showed LTP of the response. In contrast, the tetanus induced a LTD of the PSP amplitude or slope in 14 out of these 16 cells. The percentage of cells showing LTD in synaptic efficacy (87%) when the NMDA receptors activation was blocked was significantly higher than that in control-medium.

摘要

所有实验均在体外培养的大鼠前额叶皮层切片上进行。测试了2-氨基-5-磷酸戊酸(APV)对V层锥体细胞记录的突触后电位(PSP)的影响,该电位是对I-II表层进行单次或高频刺激的反应。洗脱Mg2+会增加PSP的幅度和持续时间。这种效应是由N-甲基-D-天冬氨酸(NMDA)受体的激活引起的,因为它被浴用APV所抑制。此外,在含Mg2+培养基中测试的每个细胞(N = 16)中,暴露于APV会可逆地降低PSP的单突触和多突触成分,这表明即使在对照溶液中,NMDA偶联通道的激活也促成了这些突触事件。最后,在存在Mg2+的情况下EPSP的异常电压依赖性及其对APV的敏感性表明,至少一部分NMDA受体位于突触后。对浸泡在对照或APV培养基中的细胞的传入神经施加强直刺激。长时程增强(LTP)或长时程抑制(LTD)分别定义为PSP峰值幅度或初始斜率的增加或减少,持续20分钟。在对照培养基中,34%的细胞观察到突触效能的LTP,48%的细胞观察到LTD(N = 23)。当暴露于APV时,测试的细胞(N = 16)均未显示出反应的LTP。相反,在这16个细胞中的14个细胞中,强直刺激诱导了PSP幅度或斜率的LTD。当NMDA受体激活被阻断时,显示突触效能LTD的细胞百分比(87%)显著高于对照培养基中的百分比。

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