Segregating two inhibitory circuits in human motor cortex at the level of GABAA receptor subtypes: A TMS study
Segregating two inhibitory circuits in human motor cortex at the level of GABAA receptor subtypes: A TMS study
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DOI：
10.1016/j.clinph.2007.07.005
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发表时间：
2007-10-01
影响因子：
4.7
通讯作者：
Ziernann, U.
中科院分区：
文献类型：
--
作者：
Di Lazzaro, V.;Pilato, F.;Ziernann, U.
目的：探讨人运动皮层不同神经元间回路是否通过γ -氨基丁酸A受体（GABAAR）的不同亚型介导抑制。方法：采用经颅磁刺激（TMS）方法对10名健康受试者进行两种不同形式的运动皮质抑制：短间隔皮质内抑制（SICI）和短潜伏期传入抑制（SA I）。通过单次口服三种不同的阳性GABAAR调节剂（20毫克地西泮，2.5毫克劳拉西泮和10毫克唑吡坦）对GABAAR的不同α -亚基亚型具有不同的亲和力（地西泮：非选择性，劳西泮：未知，唑吡坦：对α 1-的亲和力比α 2-或α 3亚基的GABAAR高10倍，对α 5亚基没有亲和力）的修饰，在随机交叉设计中进行了测试。此外，采用视觉模拟量表记录镇静药物的作用。结果：地西泮和劳拉西泮使SICI升高，而唑吡坦对SICI无影响。相反地西泮对SAL没有影响，而劳拉西泮和唑吡坦降低SAL，镇静作用在两种药物之间没有差异。结论：SICI和SAI的药物修饰解离模式强烈提示不同的GABAAR亚型参与了SICI和SAI。意义：我们首次为安定和唑吡坦对SAI的分离作用提供了证据，并证实了先前报道的唑吡坦与安定和劳拉西泮对SICI的不同作用。三种苯二氮松对SAI和SICI的不同影响表明，经颅磁刺激可以分离出人类运动皮层中通过不同GABAAR亚型介导抑制的神经元回路。(C) 2007年国际临床神经生理学联合会。爱思唯尔爱尔兰有限公司出版。版权所有。
Objective: To investigate if different interneuronal circuits in human motor cortex mediate inhibition through different subtypes of the gamma-aminobutyric acid A receptor (GABAAR).Methods: Two distinct forms of motor cortical inhibition were measured in 10 healthy subjects by established transcranial magnetic stimulation (TMS) protocols: short interval intracortical inhibition (SICI) and short latency afferent inhibition (SA I). Their modification by a single oral dose of three different positive GABAAR modulators (20 mg of diazepam, 2.5 mg of lorazepam and 10 mg of zolpidem) with different affinity profiles at the various alpha-subunit bearing subtypes of the GABAAR (diazepam: non-selective, lorazepam: unknown, zolpidem: 10-fold higher affinity to alpha 1- than alpha 2- or alpha 3-subunit bearing GABAARs, no affinity to alpha 5-subunits) was tested in a randomized crossover design. In addition, the sedative drug effects were recorded by a visual analogue scale.Results: Diazepam and lorazepam increased SICI, whereas zolpidem did not change SICI. In contrast, diazepam had no effect on SAL whereas lorazepam and zolpidem decreased SAL The sedative effects were not different between drugs.Conclusions: The dissociating patterns of drug modification of SICI versus SAI strongly suggest that different GABAAR subtypes are involved in SICI and SAI.Significance: We provide evidence, for the first time, for a dissociation of effects of diazepam and zolpidem on SAI and confirm the previously reported differential effect of zolpidem and of diazepam and lorazepam on SICI. The differential effects of the three benzodiaze-pines on SAI and SICI suggest that neuronal circuits in human motor cortex that mediate inhibition through different GABAAR subtypes can be segregated by TMS. (C) 2007 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.