Department of Neuroscience & Cell Biology, The University of Texas Medical Branch, Galveston, TX 77555-1069, USA.
Neuropharmacology. 2011 Dec;61(8):1334-44. doi: 10.1016/j.neuropharm.2011.08.006. Epub 2011 Aug 16.
Pain-related plasticity in the laterocapsular division of the central nucleus of the amygdala (CeLC) depends on the activation of group I metabotropic glutamate receptors (mGluRs) whereas groups II and III mGluRs generally serve inhibitory functions. Recent evidence suggests differential roles of group III subtypes mGluR7 (pain enhancing) and mGluR8 (pain inhibiting) in the amygdala (Palazzo et al., 2008). Here we addressed the underlying synaptic mechanisms of mGluR7 and mGluR8 function in the CeLC under normal conditions and in an arthritis pain model. Using patch-clamp recordings in rat brain slices, we measured monosynaptic excitatory post-synaptic currents (EPSCs), mono- and polysynaptic inhibitory synaptic currents (IPSCs), and synaptically evoked action potentials (E-S coupling) in CeLC neurons. Synaptic responses were evoked by electrical stimulation in the basolateral amygdala (BLA). A selective mGluR8 agonist (DCPG) inhibited evoked EPSCs and synaptic spiking more potently in slices from arthritic rats than in slices from normal rats. In contrast, a selective mGluR7 agonist (AMN082) increased EPSCs and E-S coupling in slices from normal rats but not in the pain model. The effects of AMN082 and DCPG were blocked by a group III antagonist (MAP4). AMN082 increased frequency, but not amplitude, of spontaneous EPSCs but had no effect on miniature EPSCs (in TTX). DCPG decreased frequency, but not amplitude, of spontaneous and miniature EPSCs. The data suggest that mGluR8 acts presynaptically to inhibit excitatory transmission whereas the facilitatory effects of mGluR7 are indirect through action potential-dependent network action. AMN082 decreased evoked IPSCs and frequency, but not amplitude, of spontaneous and miniature IPSCs in slices from normal rats. DCPG had no effect on inhibitory transmission. The results suggest that presynaptic mGluR7 inhibits inhibitory synaptic transmission to gate glutamatergic transmission to CeLC neurons under normal conditions but not in pain. Presynaptic mGluR8 inhibits pain-related enhanced excitatory transmission in the CeLC.
杏仁中央核外侧被盖区（CeLC）的疼痛相关可塑性依赖于 I 型代谢型谷氨酸受体（mGluRs）的激活，而 II 型和 III 型 mGluRs 通常发挥抑制作用。最近的证据表明，III 型亚类 mGluR7（增强疼痛）和 mGluR8（抑制疼痛）在杏仁核中发挥不同的作用（Palazzo 等人，2008 年）。在这里，我们研究了正常条件下和关节炎疼痛模型中 CeLC 中 mGluR7 和 mGluR8 功能的潜在突触机制。我们使用大鼠脑切片中的膜片钳记录技术，测量了 CeLC 神经元中的单突触兴奋性突触后电流（EPSC）、单突触和多突触抑制性突触电流（IPSC）以及突触诱发动作电位（E-S 耦联）。突触反应通过基底外侧杏仁核（BLA）的电刺激诱发。选择性 mGluR8 激动剂（DCPG）在关节炎大鼠切片中的作用比在正常大鼠切片中更强地抑制了诱发的 EPSC 和突触放电。相比之下，选择性 mGluR7 激动剂（AMN082）在正常大鼠切片中增加了 EPSC 和 E-S 耦联，但在疼痛模型中没有作用。AMN082 和 DCPG 的作用被 III 组拮抗剂（MAP4）阻断。AMN082 增加了自发性 EPSC 的频率，但不增加其幅度，但对在 TTX 中的微小 EPSC 没有影响。DCPG 降低了自发性和微小 EPSC 的频率，但不降低其幅度。数据表明，mGluR8 在前突触水平上起作用，抑制兴奋性传递，而 mGluR7 的促进作用是通过动作电位依赖性网络作用间接产生的。AMN082 降低了正常大鼠切片中诱发的 IPSC 以及自发性和微小 IPSC 的频率，但不降低其幅度。DCPG 对抑制性传递没有影响。结果表明，在正常条件下，前突触 mGluR7 抑制 CeLC 神经元的抑制性突触传递，以控制谷氨酸能传递，但在疼痛时则不抑制。前突触 mGluR8 抑制 CeLC 中的疼痛相关增强的兴奋性传递。
