The regulation of hippocampal LTP by the molecular switch, a form of metaplasticity, requires mGlu5 receptors
The regulation of hippocampal LTP by the molecular switch, a form of metaplasticity, requires mGlu5 receptors
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DOI：
10.1016/j.neuropharm.2005.05.020
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发表时间：
2005-01-01
影响因子：
4.7
通讯作者：
Collingridge, GL
中科院分区：
文献类型：
--
作者：
Bortolotto, ZA;Collett, VJ;Collingridge, GL
代谢型谷氨酸 (mGlu) 受体在海马长时程增强 (LTP) 中的作用存在争议。在本研究中，我们使用通过同源重组删除了 mGlul、mGIU(5) 或 mGIU(7) 受体的小鼠来研究这些受体亚型在 CAI 突触 LTP 中的作用。我们研究了敲除对 LTP 和分子开关的影响，分子开关是一种化塑性形式，使 LTP 对 mGlu 受体拮抗剂 MCPG（(S)α-甲基-4-羧基苯基甘氨酸）的作用不敏感。我们发现 LTP 在三种敲除以及 mGlul 和 mGIU(5) 双敲除中很容易诱导。此外，分子开关在 mGlu(1) 或 mGlu(7) 敲除中均正常运行。相比之下，分子开关在 mGIU(5) 敲除中完全不起作用，因此 MCPG 总是会阻止在已诱导 LTP 的输入中诱导额外的 LTP。 mGlu(5) 受体敲除的效果在灌注有特定 mGIU(5) 受体拮抗剂 MPEP（2-甲基-6-(苯乙炔基)-吡啶）的野生型小鼠切片中得到复制。此外，mGlu(5) 选择性激动剂 CHPG ((RS)-2-氯-5-羟基苯基甘氨酸) 设置分子开关。这些数据表明分子开关的操作需要mGlu(5)受体的激活。 (c) 2005 Elsevier Ltd. 保留所有权利。
The role of metabotropic glutamate (mGlu) receptors in long-term potentiation (LTP) in the hippocampus is controversial. In the present study, we have used mice in which the mGlul, mGIU(5) or mGIU(7) receptor has been deleted, by homologous recombination, to study the role of these receptor subtypes in LTP at CAI synapses. We investigated the effects of the knockouts on both LTP and the molecular switch, a form of metaplasticity that renders LTP insensitive to the actions of the mGlu receptor antagonist MCPG ((S)alpha-methyl-4-carboxyphenylglycine). We find that LTP is readily induced in the three knockouts and in an mGlul and mGIU(5) double knockout. In addition, the molecular switch operates normally in either the mGlu(1) or mGlu(7) knockout. In contrast, the molecular switch is completely non-functional in the mGIU(5) knockout, such that MCPG invariably blocks the induction of additional LTP in an input where LTP has already been induced. The effect of the mGlu(5) receptor knockout was replicated in wildtype mouse slices perfused with the specific mGIU(5) receptor antagonist MPEP (2-methyl-6-(phenylethynyl)-pyridine). In addition, the mGlu(5) selective agonist CHPG ((RS)-2-chloro-5-hydroxyphenylglycine) sets the molecular switch. These data demonstrate that the operation of the molecular switch requires activation of mGlu(5) receptors. (c) 2005 Elsevier Ltd. All rights reserved.