Modulation of Inhibitory Activity Markers by Intermittent Theta-burst Stimulation in Rat Cortex is NMDA-receptor Dependent
Modulation of Inhibitory Activity Markers by Intermittent Theta-burst Stimulation in Rat Cortex is NMDA-receptor Dependent
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DOI：
10.1016/j.brs.2014.02.010
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发表时间：
2014-05-01
影响因子：
7.7
通讯作者：
Funke, Klaus
中科院分区：
文献类型：
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作者：
Labedi, Adnan;Benali, Alia;Funke, Klaus
背景资料：通过经颅磁刺激施加的间歇性θ脉冲串刺激（iTBS）已被证明可以增加人类的皮质兴奋性。在大鼠脑中，它强烈减少了表达GABA合成酶谷氨酸脱羧酶（GAD 67）的67-kD同种型的神经元的数量，以及表达钙结合蛋白小清蛋白（PV）和钙结合蛋白（CB）的神经元的数量，这两种蛋白分别是快速尖峰（FS）和非FS抑制性中间神经元的特异性标记物，这表明皮质抑制作用发生了改变。目的：由于iTBS在人体中的作用已被证明是NMDA受体敏感的，我们想知道iTBS诱导的中间神经元分子表型的变化是否也对NMDA受体介导的突触能突触传递敏感。以假手术对照的方式，在免疫组织化学分析之前，对仅通过氨基甲酸乙酯或通过额外的低剂量（亚麻醉剂）或高剂量的NMDA受体拮抗剂氯胺酮轻度麻醉的大鼠施加5个600个刺激的iTBS阻断。结果：iTBS可减少GAD 67、PV和CB表达的神经元数量。除了CB，低剂量的氯胺酮部分防止这些影响，而较高剂量几乎完全取消iTBS的effects.Conclusions：我们的研究结果表明，iTBS调制的分子，也可能是电，皮层抑制性中间神经元的活动和FS型，但非FS型神经元的调制是由NMDA受体介导的。因此，iTBS与影响不同受体亚型的药理学干预的组合可以提供增强其在调节不同细胞类型的活性和防止其他细胞类型被调节中的选择性的选择。(C)2014爱思唯尔公司All rights reserved.
Background: Intermittent theta-burst stimulation (iTBS) applied via transcranial magnetic stimulation has been shown to increase cortical excitability in humans. In the rat brain it strongly reduced the number of neurons expressing the 67-kD isoform of the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD67) and those expressing the calcium-binding proteins parvalbumin (PV) and calbindin (CB), specific markers of fast-spiking (FS) and non-FS inhibitory interneurons, respectively, an indication of modified cortical inhibition.Objective: Since iTBS effects in humans have been shown to be NMDA receptor sensitive, we wondered whether the iTBS-induced changes in the molecular phenotype of interneurons may be also sensitive to glutamatergic synaptic transmission mediated by NMDA receptors.Methods: In a sham-controlled fashion, five iTBS-blocks of 600 stimuli were applied to rats either lightly anesthetized by only urethane or by an additional low (subnarcotic) or high dose of the NMDA receptor antagonist ketamine before immunohistochemical analysis. Results: iTBS reduced the number of neurons expressing GAD67, PV and CB. Except for CB, a low dose of ketamine partially prevented these effects while a higher dose almost completely abolished the iTBS effects.Conclusions: Our findings indicate that iTBS modulates the molecular, and likely also the electric, activity of cortical inhibitory interneurons and that the modulation of FS-type but less that of non-FS-type neurons is mediated by NMDA receptors. A combination of iTBS with pharmacological interventions affecting distinct receptor subtypes may thus offer options to enhance its selectivity in modulating the activity of distinct cell types and preventing others from being modulated. (C) 2014 Elsevier Inc. All rights reserved.