代谢型谷氨酸受体5（mGluR5）介导晚期长时程增强（late-LTP）、网络活动和学习之间的相互作用。

MGluR5 mediates the interaction between late-LTP, network activity, and learning.

作者信息

Bikbaev Arthur, Neyman Sergey, Ngomba Richard Teke, Conn P Jeffrey, Nicoletti Ferdinando, Manahan-Vaughan Denise

机构信息

Department of Experimental Neurophysiology, Medical Faculty, Ruhr University Bochum, Bochum, Germany.

出版信息

PLoS One. 2008 May 14;3(5):e2155. doi: 10.1371/journal.pone.0002155.

Hippocampal synaptic plasticity and learning are strongly regulated by metabotropic glutamate receptors (mGluRs) and particularly by mGluR5. Here, we investigated the mechanisms underlying mGluR5-modulation of these phenomena. Prolonged pharmacological blockade of mGluR5 with MPEP produced a profound impairment of spatial memory. Effects were associated with 1) a reduction of mGluR1a-expression in the dentate gyrus; 2) impaired dentate gyrus LTP; 3) enhanced CA1-LTP and 4) suppressed theta (5-10 Hz) and gamma (30-100 Hz) oscillations in the dentate gyrus. Allosteric potentiation of mGluR1 after mGluR5 blockade significantly ameliorated dentate gyrus LTP, as well as suppression of gamma oscillatory activity. CA3-lesioning prevented MPEP effects on CA1-LTP, suggesting that plasticity levels in CA1 are driven by mGluR5-dependent synaptic and network activity in the dentate gyrus. These data support the hypothesis that prolonged mGluR5-inactivation causes altered hippocampal LTP levels and network activity, which is mediated in part by impaired mGluR1-expression in the dentate gyrus. The consequence is impairment of long-term learning.

海马体突触可塑性和学习受到代谢型谷氨酸受体（mGluRs）的强烈调控，尤其是mGluR5。在此，我们研究了mGluR5调节这些现象的潜在机制。用MPEP对mGluR5进行长期药理学阻断会导致空间记忆严重受损。这些影响与以下因素有关：1）齿状回中mGluR1a表达的减少；2）齿状回长时程增强（LTP）受损；3）CA1区LTP增强；4）齿状回中θ波（5 - 10赫兹）和γ波（30 - 100赫兹）振荡受到抑制。mGluR5阻断后mGluR1的变构增强显著改善了齿状回LTP以及γ振荡活动的抑制。CA3区损伤可防止MPEP对CA1区LTP的影响，这表明CA1区的可塑性水平是由齿状回中mGluR5依赖的突触和网络活动驱动的。这些数据支持以下假设：mGluR5的长期失活会导致海马体LTP水平和网络活动改变，这部分是由齿状回中mGluR1表达受损介导的。其结果是长期学习受到损害。