Role of NMDA receptor subtypes in different forms of NMDA-dependent synaptic plasticity.
Role of NMDA receptor subtypes in different forms of NMDA-dependent synaptic plasticity.
复制标题
DOI：
10.1186/1471-2202-8-55
复制
发表时间：
2007-07-26
期刊：
影响因子：
2.4
通讯作者：
Wigstroem, Holger
中科院分区：
文献类型：
--
作者：
Li, Rui;Huang, Fen-Sheng;Abbas, Abdul-Karim;Wigstroem, Holger
不同的NMDAR亚基参与了多种形式的突触可塑性。然而，NMDAR亚单位在某些“非常规”可塑性形式中的作用仍存在争议。在这项研究中，我们使用亚单位特异性阻断剂来测试含有NR2A和NR2B的NMDAR在一种化学性长期抑郁(LTD)中的作用。这种抑郁是由NMDAR激动剂NMDA短暂沐浴在12-18天大鼠的海马片上引起的。为了进行比较，我们还研究了其他形式的可塑性，包括在低镁离子条件下0.1赫兹刺激引起的“慢LTD”以及长时程增强(LTP)。含有NR2a的NMDARs的阻断剂NVP-AAM077(NVP)显著减少了这两种形式的抑郁症，而含有NR2B的NMDARs的阻断剂Ro25-6981(Ro)或ifenprodil(Ife)对它们没有显著影响。LTP似乎更敏感，因为它被NVP完全阻断，被Ro或Ife部分阻断。然而，NVP的阻断作用可以通过降低灌流液中的镁离子浓度而被NMDA反应的普遍放大所抵消。在低镁溶液中记录的NMDA-EPSP上施加NVP或Ro/IFE后，反应分别减少到初始大小的70%和20%，而两种阻滞剂联合应用几乎完全取消了反应。此外，NMDA的应用与先前破伤风诱导的LTP一样，导致了一条通路的去增强，NVP但不是Ro/Ife基本上阻止了这种去增强以及控制通路的化学LTD。LTP通路上的第二次破伤风引起的再增强可被NVP完全阻断，但可被Ro/Ife部分阻断。在幼年大鼠的海马片上，所有这些结果都可以用一个简单的模型来解释，在可塑性和NMDAR介导的反应方面，NR2A亚基主导NR2B亚基。该模型表明，钙离子通过不同的NMDAR亚型流入突触后脊椎，构成一条“最终的共同途径”，通过突触的大小和时间模式控制突触的可塑性，而不受来源的影响。
The involvement of different NMDA receptor (NMDAR) subunits has been implicated in several forms of synaptic plasticity. However, it is still controversial to what extent the involvement is specific, and little is known about the role of NMDAR subunits in certain "non-conventional" forms of plasticity. In this study we used subunit-specific blockers to test the roles of NR2A- and NR2B-containing NMDARs in a type of chemical long-term depression (LTD) induced by brief bath application of the NMDAR agonist NMDA to hippocampal slices from 12–18 days old rats. For comparison, we also examined other forms of plasticity, including a "slow LTD" induced by 0.1 Hz stimulation under low Mg2+ conditions as well as long-term potentiation (LTP). A blocker of NR2A-containing NMDARs, NVP-AAM077 (NVP), substantially reduced the two forms of studied depression whereas blockers of NR2B-containing NMDARs, Ro25-6981 (Ro) or Ifenprodil (Ife), had no significant effect on them. LTP appeared to be more sensitive as it was fully blocked by NVP and partially blocked by Ro or Ife. However, the blocking effects of NVP could be counteracted by general amplification of NMDA responses by lowering Mg2+ concentration in the perfusion solution. Applying NVP or Ro/Ife on isolated NMDA-EPSPs recorded in low Mg2+ solution reduced responses to about 70% and 20% of initial size, respectively, whereas coapplication of both blockers almost completely abolished the responses. Additionally, NMDA application caused depotentiation of a pathway with prior tetanus-induced LTP, and NVP but not Ro/Ife substantially prevented that depotentiation as well as the chemical LTD of the control pathway. A second tetanus on the LTP pathway induced repotentiation which was fully blocked by NVP but partially blocked by Ro/Ife. All of these results on hippocampal slices from young rats can be explained by a simple model, in which NR2A subunits dominate over NR2B subunits with respect to both plasticity and NMDAR-mediated responses. The model suggests that Ca2+ influx into the postsynaptic spine via different subtypes of NMDARs makes up a "final common pathway", controlling synaptic plasticity by its magnitude and temporal pattern regardless of the source.
登录
查看更多内容
DOI：
10.1073/pnas.89.10.4363
发表时间：
1992-05-15
影响因子：
11.1
作者：
DUDEK, SM;BEAR, MF
通讯作者：
BEAR, MF
影响因子：
25
作者：
Li, H;Chen, AQ;Rogawski, MA
通讯作者：
Rogawski, MA
影响因子：
5.5
作者：
BLISS, TVP;GARDNERM.AR
通讯作者：
GARDNERM.AR
影响因子：
5.5
作者：
BLISS, TVP;LOMO, T
通讯作者：
LOMO, T
影响因子：
2
作者：
BASHIR, ZI;COLLINGRIDGE, GL
通讯作者：
COLLINGRIDGE, GL