Recruiting extrasynaptic NMDA receptors augments synaptic signaling
Recruiting extrasynaptic NMDA receptors augments synaptic signaling
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DOI：
10.1152/jn.01169.2007
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发表时间：
2008-02-01
影响因子：
2.5
通讯作者：
Pettit, Diana L.
中科院分区：
文献类型：
--
作者：
Harris, Alexander Z.;Pettit, Diana L.
N-甲基-D-天冬氨酸受体（NMDAR）激活可促进细胞存活或启动细胞死亡，结果取决于突触或突触外受体是否被激活。类似地，这种差异激活被提出来控制可塑性的方向。然而，激活脑切片中突触外NMDAR所需的生理参数仍然未知。使用不可逆的使用依赖性NMDAR拮抗剂MK-801分离突触外NMDAR，我们已经测试了从5到400 Hz的短刺激列激活CA 1海马切片锥体神经元上这些受体的能力。低至25 Hz的频率参与突触外NMDAR，最大激活频率在100和200 Hz之间。由于在大鼠的探索行为中发生了类似的突触输入爆发，我们的研究结果表明，“突触外”NMDAR定期参与突触传递。此外，175 Hz刺激序列激活所有可用的突触和突触外树突NMDAR，表明这些NMDAR根据需要充当突触受体，瞬时增加突触强度。因此，突触外NMDAR在突触生理学中起着至关重要的作用，这使人们对其“突触外”的地位产生了疑问。".
N-Methyl-D-aspartate receptor (NMDAR) activation may promote cell survival or initiate cell death, with the outcome dependent on whether synaptic or extrasynaptic receptors are activated. Similarly, this differential activation has been proposed to govern the direction of plasticity. However, the physiological parameters necessary to activate extrasynaptic NMDARs in brain slices remain unknown. Using the irreversible use-dependent NMDAR antagonist MK-801 to isolate extrasynaptic NMDARs, we have tested the ability of short-stimulation trains from 5 to 400 Hz to activate these receptors on CA1 hippocampal slice pyramidal neurons. Frequencies as low as 25 Hz engage extrasynaptic NMDARs, with maximal activation at frequencies between 100 and 200 Hz. Since similar bursts of synaptic input occur during exploratory behavior in rats, our results demonstrate that "extrasynaptic" NMDARs regularly participate in synaptic transmission. Further, 175-Hz-stimulation trains activate all available synaptic and extrasynaptic dendritic NMDARs, suggesting these NMDARs act as synaptic receptors as needed, transiently increasing synaptic strength. Thus extrasynaptic NMDARs play a vital role in synaptic physiology, calling into question their status as "extrasynaptic.".