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Cortical neurons and networks are dormant but fully responsive during isoelectric brain state
Brain ( IF 14.5 ) Pub Date : 2017-08-24 , DOI: 10.1093/brain/awx175
Tristan Altwegg-Boussac , Adrien E Schramm , Jimena Ballestero , Fanny Grosselin , Mario Chavez , Sarah Lecas , Michel Baulac , Lionel Naccache , Sophie Demeret , Vincent Navarro , Séverine Mahon , Stéphane Charpier

A continuous isoelectric electroencephalogram reflects an interruption of endogenously-generated activity in cortical networks and systematically results in a complete dissolution of conscious processes. This electro-cerebral inactivity occurs during various brain disorders, including hypothermia, drug intoxication, long-lasting anoxia and brain trauma. It can also be induced in a therapeutic context, following the administration of high doses of barbiturate-derived compounds, to interrupt a hyper-refractory status epilepticus. Although altered sensory responses can be occasionally observed on an isoelectric electroencephalogram, the electrical membrane properties and synaptic responses of individual neurons during this cerebral state remain largely unknown. The aim of the present study was to characterize the intracellular correlates of a barbiturate-induced isoelectric electroencephalogram and to analyse the sensory-evoked synaptic responses that can emerge from a brain deprived of spontaneous electrical activity. We first examined the sensory responsiveness from patients suffering from intractable status epilepticus and treated by administration of thiopental. Multimodal sensory responses could be evoked on the flat electroencephalogram, including visually-evoked potentials that were significantly amplified and delayed, with a high trial-to-trial reproducibility compared to awake healthy subjects. Using an analogous pharmacological procedure to induce prolonged electro-cerebral inactivity in the rat, we could describe its cortical and subcortical intracellular counterparts. Neocortical, hippocampal and thalamo-cortical neurons were all silent during the isoelectric state and displayed a flat membrane potential significantly hyperpolarized compared with spontaneously active control states. Nonetheless, all recorded neurons could fire action potentials in response to intracellularly injected depolarizing current pulses and their specific intrinsic electrophysiological features were preserved. Manipulations of the membrane potential and intracellular injection of chloride in neocortical neurons failed to reveal an augmented synaptic inhibition during the isoelectric condition. Consistent with the sensory responses recorded from comatose patients, large and highly reproducible somatosensory-evoked potentials could be generated on the inactive electrocorticogram in rats. Intracellular recordings revealed that the underlying neocortical pyramidal cells responded to sensory stimuli by complex synaptic potentials able to trigger action potentials. As in patients, sensory responses in the isoelectric state were delayed compared to control responses and exhibited an elevated reliability during repeated stimuli. Our findings demonstrate that during prolonged isoelectric brain state neurons and synaptic networks are dormant rather than excessively inhibited, conserving their intrinsic properties and their ability to integrate and propagate environmental stimuli.

中文翻译:

皮质神经元和网络处于休眠状态,但在等电脑状态下完全反应

连续的等电脑电图反映了皮质网络中内源性活动​​的中断,并有系统地导致意识过程的完全消退。这种脑电不活动发生在各种脑部疾病中,包括体温过低,药物中毒,长期缺氧和脑外伤。在给予高剂量的巴比妥酸酯衍生的化合物后,也可以在治疗环境中诱导其发作,以中断癫痫病的高难治性状态。尽管有时可以在等电脑电图上观察到改变的感觉反应,但是在这种脑状态下单个神经元的电膜特性和突触反应仍然未知。本研究的目的是表征巴比妥酸盐诱导的等电脑电图的细胞内相关性,并分析感觉剥夺的自发性电活动可能引起的感觉诱发的突触反应。我们首先检查了患有顽固性癫痫持续状态并通过使用硫喷妥钠治疗的患者的感觉反应。可以在平坦的脑电图上诱发多模式感官反应,包括明显诱发和延迟的视觉诱发电位,与觉醒的健康受试者相比,具有较高的试验到试验的可重复性。使用类似的药理学方法诱导大鼠长时间的脑电不活动,我们可以描述其皮质和皮质下细胞内对应物。新皮质 在等电状态下,海马和丘脑皮质神经元均保持沉默,并且与自发活跃的对照状态相比,其平坦的膜电位显着超极化。尽管如此,所有记录的神经元都可以响应细胞内注射的去极化电流脉冲而激发动作电位,并且保留了它们特定的固有电生理特征。在新皮层神经元中对膜电位的操纵和细胞内氯化物的注入未能显示出在等电状态下突触抑制作用的增强。与昏迷患者记录的感觉反应一致,大剂量和高度可复制的体感诱发电位可能在大鼠的非活动性皮质电图上产生。细胞内记录显示,潜在的新皮质锥体细胞通过能够触发动作电位的复杂突触电位对感觉刺激作出反应。与患者一样,等电状态下的感觉反应与对照反应相比有所延迟,并且在反复刺激过程中表现出较高的可靠性。我们的发现表明,在长时间的等电脑状态下,神经元和突触网络处于休眠状态,而不是被过度抑制,从而保留了它们的固有特性以及整合和传播环境刺激的能力。与控制响应相比,等电状态下的感觉响应被延迟,并且在重复刺激期间表现出提高的可靠性。我们的发现表明,在长时间的等电脑状态下,神经元和突触网络处于休眠状态,而不是被过度抑制,从而保留了它们的固有特性以及整合和传播环境刺激的能力。与控制响应相比,等电状态下的感觉响应被延迟,并且在重复刺激期间表现出提高的可靠性。我们的发现表明,在长时间的等电脑状态下,神经元和突触网络处于休眠状态,而不是被过度抑制,从而保留了它们的固有特性以及整合和传播环境刺激的能力。
更新日期:2017-08-24
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