Group I Metabotropic Glutamate Receptor (mGluR)-Dependent Long-Term Depression Mediated via p38 Mitogen-Activated Protein Kinase Is Inhibited by Previous High-Frequency Stimulation and Activation of mGluRs and Protein Kinase C in the Rat Dentate Gyrus In Vitro
Group I Metabotropic Glutamate Receptor (mGluR)-Dependent Long-Term Depression Mediated via p38 Mitogen-Activated Protein Kinase Is Inhibited by Previous High-Frequency Stimulation and Activation of mGluRs and Protein Kinase C in the Rat Dentate Gyrus In Vitro
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DOI：
10.1523/jneurosci.22-14-06121.2002
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发表时间：
2002-07
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影响因子：
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通讯作者：
Anthony M. Rush;Jianqun Wu;M. Rowan;R. Anwyl
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文献类型：
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作者：
Anthony M. Rush;Jianqun Wu;M. Rowan;R. Anwyl
已知突触可塑性的诱导受突触的先前历史的影响，这一过程被称为元可塑性。在这里，我们证明了一种新的metaplasticity中，第一组代谢型谷氨酸受体（mGluR）依赖的长期抑郁症（LTD）的突触传递的调节由以前的mGluR激活。在这些研究中，由选择性激动剂（RS）-3，5-二羟基苯甘氨酸（DHPG-LTD）诱导的I组mGluR依赖性LTD被先前的预处理短暂高频刺激（HFS）抑制，无论预处理HFS是否诱导长时程增强。HFS预处理时阻断NMDA受体并不改变HFS对DHPG LTD的抑制作用。然而，在预处理HFS过程中拮抗mGluRs确实阻止了HFS对DHPG-LTD的抑制。此外，阻断预处理过程中PKC的激活也可阻断HFS对DHPG-LTD的抑制作用，阻断PKC的激活并不能抑制DHPG-LTD本身，但阻断p38丝裂原活化蛋白激酶（MAPK）通路可抑制DHPG-LTD。因此，尽管DHPG-LTD是通过激活p38 MAPK途径介导的，但预处理HFS对DHPG-LTD的抑制作用是通过刺激I/II组mGluR、激活PKC和随后阻断I组mGluR的功能介导的。
The induction of synaptic plasticity is known to be influenced by the previous history of the synapse, a process termed metaplasticity. Here we demonstrate a novel metaplasticity in which group I metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD) of synaptic transmission is regulated by previous mGluR activation. In these studies, the group I mGluR-dependent LTD induced by the selective agonist (RS)-3,5-dihydroxyphenylglycine (DHPG-LTD) was inhibited by previous preconditioning brief high-frequency stimulation (HFS), regardless of whether the preconditioning HFS induced long-term potentiation. Blockade of NMDA receptors during the preconditioning HFS did not alter the inhibition of DHPG-LTD by the HFS. However, antagonism of mGluRs during the preconditioning HFS did prevent the inhibition of DHPG-LTD by the HFS. In addition, blocking PKC stimulation during the preconditioning HFS also prevented the inhibitory effect of HFS on DHPG-LTD. The DHPG-LTD itself was not inhibited by blocking PKC stimulation but was inhibited by blocking the p38 mitogen-activated protein kinase (MAPK) pathway. Thus, whereas the DHPG-LTD is mediated via activation of the p38 MAPK pathway, the inhibitory effects of preconditioning HFS on DHPG-LTD are mediated via stimulation of group I/II mGluRs, activation of PKC, and subsequent blocking of the functioning of group I mGluR.