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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Enhancement of CA3 hippocampal network activity by activation of group II metabotropic glutamate receptors
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Enhancement of CA3 hippocampal network activity by activation of group II metabotropic glutamate receptors

机译：通过激活II型代谢型谷氨酸受体增强CA3海马网络活性

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摘要

Impaired function or expression of group II metabotropic gluta mate receptors (mGluRlls) is observed in brain disorders such as schizophrenia. This class of receptor is thought to modulate activity of neuronal circuits primarily by inhibiting neurotransmit ter release. Here, we characterize a postsynaptic excitatory re sponse mediated by somato-dendritic mGluRlls in hippocampal CA3 pyramidal cells and in stratum oriens interneurons. The spe cific 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 mGluRMs were blocked. Thus, our data indicate that hippocampal responses are modulated not only by presynaptic mGluRlls that reduce gluta mate release but also by postsynaptic mGluRlls that depolarize neurons and enhance CA3 network activity.
机译：在诸如精神分裂症的脑部疾病中观察到II族代谢型谷氨酸伴侣受体（mGluRlls）的功能或表达受损。认为这类受体主要通过抑制神经递质的释放来调节神经元回路的活性。在这里，我们表征了海马CA3锥体细胞和间层神经元中体树突状mGluRlls介导的突触后兴奋反应。特定的mGluRII激动剂DCG-IV或LCCG-1诱导了被mGluRII拮抗剂LY341495阻断的内向电流。转基因小鼠的实验表明，mGluR3〜（-/-）小鼠的内向电流显着降低，而mGluR2〜（-/-）小鼠却没有。兴奋反应与theta频率的同步活动周期有关。此外，当mGluRM被阻断时，胆碱能引起的网络振荡表现出降低的频率。因此，我们的数据表明，海马反应不仅受到降低谷氨酸释放的突触前mGluRlls的调节，而且还受到使神经元去极化并增强CA3网络活性的突触后mGluRlls的调节。

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    Jeanne Ster; Jose Maria Mateos; Benjamin Friedrich Grewe; Guyllaume Coiret; Corrado Corti; Mauro Corsi; Fritjof Helmchen; Urs Gerber;

  • 作者单位

    Brain Research Institute, University of Zurich, CH-8057 Zurich, Switzerland;

    Brain Research Institute, University of Zurich, CH-8057 Zurich, Switzerland,Center for Microscopy and Image Analysis, University of Zurich, CH-8057 Zurich, Switzerland;

    Brain Research Institute, University of Zurich, CH-8057 Zurich, Switzerland;

    Brain Research Institute, University of Zurich, CH-8057 Zurich, Switzerland;

    Department of Biology, Neuroscience Centre of Excellence in Drug Discovery, GlaxoSmithKline Medicines Research Centre,37135 Verona, Italy;

    Department of Biology, Neuroscience Centre of Excellence in Drug Discovery, GlaxoSmithKline Medicines Research Centre,37135 Verona, Italy;

    Brain Research Institute, University of Zurich, CH-8057 Zurich, Switzerland;

    Brain Research Institute, University of Zurich, CH-8057 Zurich, Switzerland;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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