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代谢型谷氨酸受体在苔藓纤维长时程增强中作用的反面证据:突变小鼠及药理学拮抗剂的应用

Evidence against a role for metabotropic glutamate receptors in mossy fiber LTP: the use of mutant mice and pharmacological antagonists.

作者信息

Hsia A Y, Salin P A, Castillo P E, Aiba A, Abeliovich A, Tonegawa S, Nicoll R A

机构信息

Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143-0450, USA.

出版信息

Neuropharmacology. 1995 Nov;34(11):1567-72. doi: 10.1016/0028-3908(95)00115-m.

DOI:10.1016/0028-3908(95)00115-m
PMID:8606804
Abstract

We have used a number of approaches to address a possible role of metabotropic glutamate receptors (mGluRs) in mossy fiber long-term potentiation (LTP) in the hippocampus. We have used two types of mutant mice--one lacking the mGluR1 subtype of receptor and one lacking the gamma isoform of protein kinase C. In neither type of mouse did we find any alteration in the magnitude of mossy fiber LTP. We next examined whether mGluRs might modulate the magnitude and/or threshold for the induction of mossy fiber LTP. In these experiments we used tetani that were either just subthreshold or just suprathreshold for generating LTP. The mGluR antagonist (+)-alpha-methyl-4-carboxyphenylglycine [(+)MCPG] did not convert a subthreshold tetanus into a suprathreshold tetanus, nor did (+)MCPG have any effect on the small amount of LTP that was generated by a just suprathreshold tetanus. Based on our studies, we have been unable to identify a role for mGluRs in mossy fiber LTP.

摘要

我们采用了多种方法来研究代谢型谷氨酸受体(mGluRs)在海马体苔藓纤维长时程增强(LTP)中可能发挥的作用。我们使用了两种类型的突变小鼠——一种缺乏mGluR1受体亚型,另一种缺乏蛋白激酶C的γ亚型。在这两种类型的小鼠中,我们均未发现苔藓纤维LTP的幅度有任何改变。接下来,我们研究了mGluRs是否可能调节苔藓纤维LTP诱导的幅度和/或阈值。在这些实验中,我们使用了刚好低于阈值或刚好高于阈值以产生LTP的强直刺激。mGluR拮抗剂(+)-α-甲基-4-羧基苯甘氨酸[(+)MCPG]既没有将低于阈值的强直刺激转变为高于阈值的强直刺激,对于刚好高于阈值的强直刺激所产生的少量LTP,(+)MCPG也没有任何影响。基于我们的研究,我们无法确定mGluRs在苔藓纤维LTP中的作用。

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