Enhanced group II mGluR-mediated inhibition of pain-related synaptic plasticity in the amygdala.

Enhanced group II mGluR-mediated inhibition of pain-related synaptic plasticity in the amygdala.
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DOI:
10.1186/1744-8069-2-18
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发表时间:
2006-05-08
期刊:
影响因子:
3.3
通讯作者:
Neugebauer V
Neugebauer V
中科院分区:
医学3区
文献类型:
--
作者:
Han JS;Fu Y;Bird GC;Neugebauer V

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杏仁中央核的外侧囊部分(CeLC)是脊髓-臂旁-杏仁核疼痛通路的靶点。我们先前的研究表明,CeLC神经元在关节炎疼痛的高岭土/角叉菜胶模型中发展突触可塑性和增加的神经元兴奋性。这些疼痛相关的变化涉及突触前I组代谢型谷氨酸受体(mGluRs)和突触后NMDA和降钙素基因相关肽(CGRP 1)受体。在这里,我们解决了第二组mGluRs的作用。从来自对照大鼠和关节炎大鼠(将高岭土/角叉菜胶注射到膝盖中后>6小时)的脑切片中的CeLC神经元进行全细胞电流钳和电压钳记录。电刺激桥臂旁区传入纤维诱发单突触兴奋性突触后电流。选择性II组mGluR激动剂(LY 354740)降低关节炎大鼠CeLC神经元EPSC的幅度(IC 50 = 0.59 nM)比对照动物(IC 50 = 15.0 nM)更有效。LY 354740的抑制作用被II组mGluR拮抗剂(EGLU)逆转,但不是GABAA受体拮抗剂(荷包牡丹碱)。LY 354740降低TTX存在下微型EPSC的频率,但不降低振幅。未检测到神经元兴奋性指标(膜斜率电导和动作电位放电率)的显著变化。我们的数据表明,第二组mGluRs的行为突触前调节突触可塑性在杏仁核的关节炎疼痛模型。
The latero-capsular part of the central nucleus of the amygdala (CeLC) is the target of the spino-parabrachio-amygdaloid pain pathway. Our previous studies showed that CeLC neurons develop synaptic plasticity and increased neuronal excitability in the kaolin/carrageenan model of arthritic pain. These pain-related changes involve presynaptic group I metabotropic glutamate receptors (mGluRs) and postsynaptic NMDA and calcitonin gene-related peptide (CGRP1) receptors. Here we address the role of group II mGluRs. Whole-cell current- and voltage-clamp recordings were made from CeLC neurons in brain slices from control rats and arthritic rats (>6 h postinjection of kaolin/carrageenan into the knee). Monosynaptic excitatory postsynaptic currents (EPSCs) were evoked by electrical stimulation of afferents from the pontine parabrachial (PB) area. A selective group II mGluR agonist (LY354740) decreased the amplitude of EPSCs more potently in CeLC neurons from arthritic rats (IC50 = 0.59 nM) than in control animals (IC50 = 15.0 nM). The inhibitory effect of LY354740 was reversed by a group II mGluR antagonist (EGLU) but not a GABAA receptor antagonist (bicuculline). LY354740 decreased frequency, but not amplitude, of miniature EPSCs in the presence of TTX. No significant changes of neuronal excitability measures (membrane slope conductance and action potential firing rate) were detected. Our data suggest that group II mGluRs act presynaptically to modulate synaptic plasticity in the amygdala in a model of arthritic pain.
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发表时间: 2002-01-01
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