Endomorphin-1 modulates intrinsic inhibition in the dorsal vagal complex
Endomorphin-1 modulates intrinsic inhibition in the dorsal vagal complex
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DOI：
10.1152/jn.00336.2007
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发表时间：
2007-09-01
影响因子：
2.5
通讯作者：
Smith, Bret N.
中科院分区：
文献类型：
--
作者：
Glatzer, Nicholas R.;Derbenev, Andrei V.;Smith, Bret N.
μ-阿片受体（莫尔）激动剂通过调节孤束核（NTS）和迷走神经背侧运动核（DMV）中的神经元而深刻地影响消化和其它自主神经功能。从大鼠和转基因小鼠的脑干切片中的NTS和DMV神经元进行全细胞记录，所述大鼠和转基因小鼠在GAD 67启动子的控制下表达增强型绿色荧光蛋白（EGFP）（EGFP-GABA神经元），以鉴定阿片样物质介导的对GABA能回路的作用。评估了EGFP-GABA神经元的突触和膜特性。内源性选择性莫尔激动剂内吗啡肽-1（EM-1）减少大鼠和小鼠DMV神经元中的自发和诱发兴奋性突触后电流（EPSC）和抑制性突触后电流（IPSC）。电刺激孤束诱发恒定潜伏期的EPSCs在类似的50%的EGFP-GABA神经元，EM-1的应用和反应减少。EM-1减少动作电位放电，EGFP-GABA神经元突触输入的频率和幅度以及对直接谷氨酸刺激的反应。EGFP-GABA神经元的一个子集共定位mRFP 1后逆行，transneuronal感染后，胃接种PRV-614，表明它们与胃投射DMV神经元突触。完整NTS投射的谷氨酸光解刺激在DMV神经元中诱发IPSC，EM-1减少诱发反应，最有可能是通过激活NTS中运动前GABA神经元的索马上的莫尔。莫尔拮抗剂纳洛酮或H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH 2（CTAP）阻断EM-1的作用。结果表明，孤束核的GABA神经元接受迷走神经的直接传入，并投射到胃相关的DMV神经元。此外，迷走神经复合体的特定成分的EM-1的调制通过作用于不同的受体位置而差异地抑制对DMV的兴奋性和抑制性突触输入。
Mu-opioid receptor (MOR) agonists profoundly influence digestive and other autonomic functions by modulating neurons in nucleus tractus solitarius (NTS) and dorsal motor nucleus of the vagus (DMV). Whole cell recordings were made from NTS and DMV neurons in brain stem slices from rats and transgenic mice that expressed enhanced green fluorescent protein (EGFP) under the control of a GAD67 promoter (EGFP-GABA neurons) to identify opioid-mediated effects on GABAergic circuitry. Synaptic and membrane properties of EGFP-GABA neurons were assessed. The endogenous selective MOR agonist endomorphin-1 (EM-1) reduced spontaneous and evoked excitatory postsynaptic currents (EPSCs) and inhibitory postsynaptic currents (IPSCs) in both rat and mouse DMV neurons. Electrical stimulation of the solitary tract evoked constant-latency EPSCs in similar to 50% of EGFP-GABA neurons, and the responses were reduced by EM-1 application. EM-1 reduced action potential firing, the frequency and amplitude of synaptic inputs in EGFP-GABA neurons and responses to direct glutamate stimulation. A subset of EGFP-GABA neurons colocalized mRFP1 after retrograde, transneuronal infection after gastric inoculation with PRV-614, indicating that they synapsed with gastric-projecting DMV neurons. Glutamate photolysis stimulation of intact NTS projections evoked IPSCs in DMV neurons, and EM-1 reduced the evoked response, most likely by activation of MOR on the soma of premotor GABA neurons in NTS. Naltrexone or H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 ( CTAP), MOR antagonists, blocked the effects of EM-1. Our results show that GABA neurons in the NTS receive direct vagal afferent input and project to gastric-related DMV neurons. Furthermore, modulation by EM-1 of specific components of the vagal complex differentially suppresses excitatory and inhibitory synaptic input to the DMV by acting at different receptor locations.