Gereau R W, Conn P J
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
J Neurosci. 1995 Oct;15(10):6879-89. doi: 10.1523/JNEUROSCI.15-10-06879.1995.
The metabotropic glutamate receptors (mGluRs) have many important roles in regulation of neuronal excitability and synaptic transmission. In hippocampal area CA1, activation of mGluRs can reduce both excitatory and inhibitory synaptic transmission. The conventional view is that the presynaptic effects are mediated by L-2-amino-4-phosphonobutyric acid (L-AP4)-sensitive, or group III mGluRs (mGluR4, mGluR6, mGluR7, mGluR8). However, some studies suggest that other mGluR subtypes may also be involved in regulation of excitatory and inhibitory synaptic transmission in area CA1. We have found that two pharmacologically distinct presynaptic receptors are involved in the depression of excitatory transmission at the Schaffer collateral--CA1 synapse. Consistent with previous studies, one receptor subtype is an L-AP4-sensitive receptor that is pharmacologically similar to mGluR4 or mGluR7. However, we have found that a second mGluR subtype, which is pharmacologically similar to mGluR1 and mGluR5 (group I mGluRs), can also reduce excitatory synaptic transmission in area CA1. Analysis of effects of agonists of these two receptors on miniature EPSCs and paired-pulse facilitation suggest that both receptors are localized presynaptically. It is also shown that the mGluR that reduces transmission at inhibitory synapses in area CA1 is presynaptically localized, is insensitive to L-AP4, and is sensitive to agonists selective for mGluR1 and mGluR5.
代谢型谷氨酸受体（mGluRs）在调节神经元兴奋性和突触传递方面具有许多重要作用。在海马CA1区，mGluRs的激活可降低兴奋性和抑制性突触传递。传统观点认为，突触前效应是由L-2-氨基-4-膦酸丁酸（L-AP4）敏感的或III组mGluRs（mGluR4、mGluR6、mGluR7、mGluR8）介导的。然而，一些研究表明，其他mGluR亚型也可能参与CA1区兴奋性和抑制性突触传递的调节。我们发现，两种药理学上不同的突触前受体参与了Schaffer侧支-CA1突触处兴奋性传递的抑制。与先前的研究一致，一种受体亚型是对L-AP4敏感的受体，在药理学上与mGluR4或mGluR7相似。然而，我们发现，另一种在药理学上与mGluR1和mGluR5（I组mGluRs）相似的mGluR亚型，也能降低CA1区的兴奋性突触传递。对这两种受体激动剂对微小兴奋性突触后电流（mEPSCs）和双脉冲易化的影响分析表明，这两种受体均定位于突触前。研究还表明，在CA1区抑制性突触处降低传递的mGluR定位于突触前，对L-AP4不敏感，对mGluR1和mGluR5选择性激动剂敏感。
