GABAA receptor subtype specific enhancement of inhibition in human motor cortex
GABAA receptor subtype specific enhancement of inhibition in human motor cortex
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DOI：
10.1113/jphysiol.2006.114694
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发表时间：
2006-09-15
影响因子：
5.5
通讯作者：
Ziemann, Ulf
中科院分区：
文献类型：
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作者：
Di Lazzaro, Vincenzo;Pilato, Fabio;Ziemann, Ulf
抑制对于调节皮层回路的活动具有根本的重要性。抑制作用是通过多种不同的中间神经元和γ-氨基丁酸A受体（GABA（A）R）亚型介导的。在这里，我们采用成对脉冲经颅磁刺激（TMS）来测量短间隔皮层内抑制（SICI），GABA（A）R介导的抑制在人类运动皮层，以解决的问题，GABA（A）R亚型是负责这种形式的抑制。研究表明，经典的苯二氮卓类药物（地西泮和劳拉西泮）对GABA（A）R的不同α亚基亚型具有非选择性亲和力，而唑吡坦对α 1亚基GABA（A）R的亲和力是对α 2或α 3亚基GABA（A）R亲和力的10倍。我们发现，在7名健康受试者中，单次口服20 mg地西泮或2.5 mg劳拉西泮显著增加了SICI，而10 mg唑吡坦没有改变SICI。尽管所有三种药物具有相同的镇静作用，但仍发生了这种解离，这是α 1亚基GABA（A）R介导的作用。研究结果强烈表明，SICI不是由GABA（A）R的α 1亚基亚型介导的，而是由α 2或α 3亚基介导的。本研究代表了一种尝试，通过经颅磁刺激，以确定GABA（A）R亚型的具体行动，在系统水平的人类皮层，一个高度相关的问题，因为不同的α-亚基轴承亚型的GABA（A）R不同地参与苯二氮卓类介导的影响，如镇静，健忘症或抗焦虑，在发育皮层可塑性，并在神经系统疾病，如癫痫。
Inhibition is of fundamental importance to regulate activity in cortical circuits. Inhibition is mediated through a diversity of different interneurones and gamma-aminobutyric acid A receptor (GABA(A)R) subtypes. Here we employed paired-pulse transcranial magnetic stimulation (TMS) to measure short interval intracortical inhibition (SICI), a GABA(A)R-mediated inhibition in human motor cortex, to address the question of which GABA(A)R subtype is responsible for this form of inhibition. It has been shown that classical benzodiazepines (diazepam and lorazepam) have a non-selective affinity profile at different alpha-subunit-bearing subtypes of the GABA(A)R while zolpidem has a 10-fold greater affinity to the alpha 1-subunit-bearing GABA(A)R compared with those bearing the alpha 2- or alpha 3-subunit. We found that, in seven healthy subjects, a single oral dose of 20 mg of diazepam or 2.5 mg of lorazepam significantly increased SICI, whereas 10 mg of zolpidem did not change SICI. This dissociation occurred despite equal sedation by all three drugs, an alpha 1-subunit GABA(A)R-mediated effect. The findings strongly suggest that SICI is not mediated by the alpha 1-subunit-bearing subtype of the GABA(A)R but by those bearing either the alpha 2- or alpha 3-subunit. This study represents an attempt by means of TMS to identify GABA(A)R subtype-specific action at the systems level of human cortex, a highly relevant issue because the different alpha-subunit-bearing subtypes of the GABA(A)R are differently involved in benzodiazepine-mediated effects such as sedation, amnesia or anxiolysis, in developmental cortical plasticity, and in neurological disorders such as epilepsy.