1 Institut National de la Santé et de la Recherche Médicale Unité 901, 13009 Marseille, France 2 Aix-Marseille Université, Unité Mixte de Recherche S901, 13009 Marseille, France 3 Institut de Neurobiologie de la Méditerranée, 13009 Marseille, France.
4 Institut des Neurosciences des Systèmes, Institut National de la Santé et de la Recherche Médicale Unité 1106, 13005 Marseille, France.
Brain. 2015 Oct;138(Pt 10):2875-90. doi: 10.1093/brain/awv227. Epub 2015 Aug 13.
Epilepsy is characterized by recurrent seizures and brief, synchronous bursts called interictal spikes that are present in-between seizures and observed as transient events in EEG signals. While GABAergic transmission is known to play an important role in shaping healthy brain activity, the role of inhibition in these pathological epileptic dynamics remains unclear. Examining the microcircuits that participate in interictal spikes is thus an important first step towards addressing this issue, as the function of these transient synchronizations in either promoting or prohibiting seizures is currently under debate. To identify the microcircuits recruited in spontaneous interictal spikes in the absence of any proconvulsive drug or anaesthetic agent, we combine a chronic model of epilepsy with in vivo two-photon calcium imaging and multiunit extracellular recordings to map cellular recruitment within large populations of CA1 neurons in mice free to run on a self-paced treadmill. We show that GABAergic neurons, as opposed to their glutamatergic counterparts, are preferentially recruited during spontaneous interictal activity in the CA1 region of the epileptic mouse hippocampus. Although the specific cellular dynamics of interictal spikes are found to be highly variable, they are consistently associated with the activation of GABAergic neurons, resulting in a perisomatic inhibitory restraint that reduces neuronal spiking in the principal cell layer. Given the role of GABAergic neurons in shaping brain activity during normal cognitive function, their aberrant unbalanced recruitment during these transient events could have important downstream effects with clinical implications.
癫痫的特征是反复发作和短暂的同步爆发，称为发作间期棘波，这些棘波出现在发作之间，在脑电图信号中表现为短暂事件。虽然 GABA 能传递被认为在塑造健康的大脑活动中发挥重要作用，但抑制在这些病理性癫痫动态中的作用仍不清楚。因此，检查参与发作间期棘波的微电路是解决这个问题的重要第一步，因为这些短暂同步在促进或抑制癫痫发作中的作用目前仍存在争议。为了在没有任何促惊厥药物或麻醉剂的情况下识别自发发作间期棘波中募集的微电路，我们将慢性癫痫模型与体内双光子钙成像和多单位细胞外记录相结合，以绘制在自由奔跑于自我调节跑步机上的小鼠 CA1 神经元中的大群体中的细胞募集情况。我们表明，在癫痫小鼠海马体的 CA1 区，与谷氨酸能神经元相反，GABA 能神经元在自发发作间期活动中优先募集。尽管发作间期棘波的特定细胞动力学发现具有高度可变性，但它们始终与 GABA 能神经元的激活相关，导致周围抑制性抑制减少主细胞层中的神经元放电。鉴于 GABA 能神经元在正常认知功能期间塑造大脑活动的作用，它们在这些短暂事件中的异常不平衡募集可能具有重要的下游影响，具有临床意义。
