Modulation of synaptic transmission from primary afferents to spinal substantia gelatinosa neurons by group III mGluRs in GAD65-EGFP transgenic mice
Modulation of synaptic transmission from primary afferents to spinal substantia gelatinosa neurons by group III mGluRs in GAD65-EGFP transgenic mice
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DOI：
10.1152/jn.00108.2010
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发表时间：
2011-03-01
影响因子：
2.5
通讯作者：
Kim, Sang Jeong
中科院分区：
文献类型：
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作者：
Cui, Lian;Kim, Yoo Rim;Kim, Sang Jeong
崔L，Kim YR，Kim HY，Lee SC，Shin H，Szabo G，Erdelii F，Kim J，Kim SJ。 GAD65-EGFP 转基因小鼠中 III 组 mGluR 对从初级传入神经到脊髓胶质神经元的突触传递的调节。 《神经生理学杂志》105：1102-1111，2011 年。首次发表于 2010 年 12 月 22 日； doi: 10.1152/jn.00108.2010.-第 III 组代谢型谷氨酸受体 (mGluR) 参与脊髓中的伤害性传递。然而，III 类 mGluRs 调节从伤害性初级传入神经到背角神经元的突触传递的细胞机制仍有待探索。在这项研究中，我们使用在谷氨酸脱羧酶 (GAD) 65 启动子控制下表达增强型绿色荧光蛋白 (EGFP) 的转基因小鼠来鉴定 GABA 能抑制性中间神经元的特定亚群。通过 GABA 免疫标记，我们证实大多数表达 GAD65-EGFP 的神经元都是 GABA 能的。因为之前没有详细检查过表达 GAD65-EGFP 的神经元，所以我们首先研究了脊髓背角凝胶质 (SG) 中表达 GAD65-EGFP 和非 EGFP 的神经元的生理特性。这两组神经元的膜特性，如静息膜电位、膜电容、动作电位阈值和动作电位高度，存在显着差异。大多数表达 EGFP 的神经元表现出强直放电模式（记录的神经元的 73%）并接收单突触 A delta 和/或 C 初级传入输入（记录的神经元的 85%）。相比之下，我们在 53% 不表达 EGFP 的神经元中观察到延迟放电模式。在确定了表达 EGFP 的神经元的生理特性后，我们测试了 III 组 mGluR 对突触传递药理学的影响。 III 组 mGluR 激动剂 L-AP4 减弱 A δ 纤维诱发的突触传递，但不影响 C 纤维诱发的向表达 EGFP 的神经元的突触传递。在不表达 EGFP 的神经元中也观察到 L-AP4 类似的初级传入特异性抑制。此外，选择性 mGluR7 激动剂 AMN082 抑制了 δ 纤维诱发的突触传递。这些结果表明，III族mGluR激动剂对从初级传入神经元到SG神经元的突触传递的调节对于伤害性初级传入神经元的类型是特异性的，但对于目标神经元的类型不是特异性的。
Cui L, Kim YR, Kim HY, Lee SC, Shin H, Szabo G, Erdelyi F, Kim J, Kim SJ. Modulation of synaptic transmission from primary afferents to spinal substantia gelatinosa neurons by group III mGluRs in GAD65-EGFP transgenic mice. J Neurophysiol 105: 1102-1111, 2011. First published December 22, 2010; doi: 10.1152/jn.00108.2010.-Group III metabotropic glutamate receptors (mGluRs) are involved in nociceptive transmission in the spinal cord. However, the cellular mechanism underlying the modulation of synaptic transmission from nociceptive primary afferents to dorsal horn neurons by group III mGluRs has yet to be explored. In this study, we used transgenic mice expressing enhanced green fluorescent protein (EGFP) under the control of the glutamate decarboxylase (GAD) 65 promoter to identify specific subpopulations of GABAergic inhibitory interneurons. By GABA immunolabeling, we confirmed the majority of GAD65-EGFP-expressing neurons were GABAergic. Because GAD65-EGFP-expressing neurons have not been examined in detail before, we first investigated the physiological properties of GAD65-EGFP- and non-EGFP-expressing neurons in substantia gelatinosa (SG) of the spinal dorsal horn. Membrane properties, such as the resting membrane potential, membrane capacitance, action potential threshold, and action potential height, differed significantly between these two groups of neurons. Most EGFP-expressing neurons displayed a tonic firing pattern (73% of recorded neurons) and received monosynaptic A delta and/or C primary afferent inputs (85% of recorded neurons). In contrast, we observed a delayed firing pattern in 53% of non-EGFP-expressing neurons. After identifying the physiological properties of EGFP-expressing neurons, we tested the effects of group III mGluRs on synaptic transmission pharmacologically. A group III mGluR agonist, L-AP4, attenuated A delta fiber-evoked synaptic transmission but did not affect C fiber-evoked synaptic transmission to EGFP-expressing neurons. Similar primary afferent-specific inhibition by L-AP4 was also observed in non-EGFP-expressing neurons. Moreover, A delta fiber-evoked synaptic transmission was suppressed by a selective mGluR7 agonist, AMN082. These results suggest that modulation of the synaptic transmission from primary afferents to SG neurons by group III mGluR agonist is specific to the type of nociceptive primary afferents but not to the type of target neurons.