Regulation of synaptic plasticity by mGluR(1) studied in vivo in mGluR(1) mutant mice

被引:33
作者
Bordi, F [1 ]
Reggiani, A [1 ]
Conquet, F [1 ]
机构
[1] GLAXO WELLCOME INC,INST MOL BIOL,GENEVA,SWITZERLAND
关键词
glutamate metabotropic receptor; long term potentiation; paired pulse; knock outs; mouse; in vivo;
D O I
10.1016/S0006-8993(97)00320-X
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The role of the metabotropic glutamate receptor 1 (mGluR(1)) in synaptic plasticity was investigated in vivo in the intact hippocampus of mutant mice lacking this receptor. In a previous study we showed reduced long-term potentiation (LTP) in the dentate gyrus of mGluR(1) -/- mice in vivo, but not when LTP was studied in a slice preparation. A possible explanation of this difference is that dentate neurons receive more inhibitory synaptic drive in vivo than in slice preparation where many inhibitory axon collaterals are lost. We report here that another form of synaptic plasticity, paired-pulse depression of the population spike, is also abnormal in the dentate gyrus of mGluR(1)-deficient mice when tested in vivo. In wild-type mice, stimulation of the medial perforant path produced paired-pulse depression of inter-pulse intervals (IPIs) up to 30 ms. Mutant mGluR(1), on the other hand, showed a significantly longer IPI depression, up to 50 ms. Paired-pulse depression results from the activation of inhibitory interneurons. The GABA(A) agonist baclofen, acting presynaptically on the GABA interneurons, attenuated paired-pulse depression and allowed for a normal and stable LTP in mGluR(1) mutant mice. These findings suggest an indirect role for mGluR(1) in synaptic plasticity via a regulation of GABA inhibition.
引用
收藏
页码:121 / 126
页数:6
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