Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013, Paris, France.
UPMC Univ Paris 06, F-75005, Paris, France.
Brain. 2017 Sep 1;140(9):2381-2398. doi: 10.1093/brain/awx175.
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.
持续等电脑电图反映了皮质网络中内源性活动的中断，并系统地导致意识过程的完全溶解。这种电脑无活性发生在各种脑疾病中，包括低温、药物中毒、长时间缺氧和脑外伤。它也可以在治疗环境中通过给予高剂量的巴比妥类化合物来诱导，以中断超敏状态的癫痫发作。虽然在等电脑电图上偶尔可以观察到改变的感觉反应，但在这种脑状态下，单个神经元的电膜特性和突触反应在很大程度上仍然未知。本研究的目的是描述巴比妥类药物诱导的等电脑电图的细胞内相关性，并分析从自发电活动中丧失的大脑中可能出现的感觉诱发突触反应。我们首先检查了患有难治性癫痫持续状态并接受硫喷妥钠治疗的患者的感觉反应能力。可以在平坦的脑电图上诱发多模态感觉反应，包括视觉诱发电位，与清醒健康受试者相比，其明显放大和延迟，具有高的试验间可重复性。使用类似的药理学程序在大鼠中诱导长时间的电脑无活性，我们可以描述其皮质和皮质下的细胞内对应物。在等电状态下，新皮层、海马和丘脑皮质神经元均处于沉默状态，与自发活动对照状态相比，其膜电位明显超极化。尽管如此，所有记录的神经元都可以对细胞内注入的去极化电流脉冲产生动作电位，并且保留了其特定的内在电生理特征。在新皮层神经元中操纵膜电位和细胞内注入氯离子未能在等电条件下揭示增强的突触抑制。与昏迷患者记录的感觉反应一致，在大鼠的无活性脑电图上可以产生大的且高度可重复的体感诱发电位。细胞内记录显示，潜在的新皮层锥体神经元通过能够触发动作电位的复杂突触电位对感觉刺激做出反应。与对照反应相比，在等电状态下感觉反应延迟，并且在重复刺激时表现出更高的可靠性。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，而不是过度抑制，保持其内在特性和整合和传播环境刺激的能力。
