Brain Research Institute, University of Zurich, CH-8057 Zurich, Switzerland.
Proc Natl Acad Sci U S A. 2011 Jun 14;108(24):9993-7. doi: 10.1073/pnas.1100548108. Epub 2011 May 31.
Impaired function or expression of group II metabotropic glutamate receptors (mGluRIIs) is observed in brain disorders such as schizophrenia. This class of receptor is thought to modulate activity of neuronal circuits primarily by inhibiting neurotransmitter release. Here, we characterize a postsynaptic excitatory response mediated by somato-dendritic mGluRIIs in hippocampal CA3 pyramidal cells and in stratum oriens interneurons. The specific mGluRII agonists DCG-IV or LCCG-1 induced an inward current blocked by the mGluRII antagonist LY341495. Experiments with transgenic mice revealed a significant reduction of the inward current in mGluR3(-/-) but not in mGluR2(-/-) mice. The excitatory response was associated with periods of synchronized activity at theta frequency. Furthermore, cholinergically induced network oscillations exhibited decreased frequency when mGluRIIs were blocked. Thus, our data indicate that hippocampal responses are modulated not only by presynaptic mGluRIIs that reduce glutamate release but also by postsynaptic mGluRIIs that depolarize neurons and enhance CA3 network activity.
在精神分裂症等脑部疾病中，观察到 II 型代谢型谷氨酸受体（mGluRIIs）的功能或表达受损。这类受体被认为主要通过抑制神经递质释放来调节神经元回路的活动。在这里，我们描述了海马 CA3 锥体神经元和齿状回门区中间神经元中由 somato-dendritic mGluRII 介导的突触后兴奋性反应。特定的 mGluRII 激动剂 DCG-IV 或 LCCG-1 诱导被 mGluRII 拮抗剂 LY341495 阻断的内向电流。在 mGluR3(-/-)而不是 mGluR2(-/-)转基因小鼠中的实验表明，内向电流显著减少。兴奋性反应与θ频率的同步活动期有关。此外，当阻断 mGluRII 时，胆碱能诱导的网络振荡的频率降低。因此，我们的数据表明，海马体的反应不仅受到减少谷氨酸释放的突触前 mGluRII 的调节，还受到去极化神经元和增强 CA3 网络活动的突触后 mGluRII 的调节。
