GABAergic inhibition shapes interictal dynamics in awake epileptic mice
GABAergic inhibition shapes interictal dynamics in awake epileptic mice
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DOI：
10.1093/brain/awv227
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发表时间：
2015-10-01
期刊：
影响因子：
14.5
通讯作者：
Cossart, Rosa
中科院分区：
文献类型：
--
作者：
Muldoon, Sarah Feldt;Villette, Vincent;Cossart, Rosa
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，其存在于发作之间，并在EEG信号中观察到短暂事件。虽然已知GABA能传递在形成健康的大脑活动中起重要作用，但抑制在这些病理性癫痫动力学中的作用仍不清楚。因此，检查参与发作间期尖峰的微电路是解决这个问题的重要的第一步，因为这些瞬时同步在促进或禁止癫痫发作中的功能目前正在辩论中。为了识别在没有任何促惊厥药物或麻醉剂的情况下自发发作间期尖峰中招募的微电路，我们将癫痫的慢性模型与体内双光子钙成像和多单位细胞外记录相结合，以在自由在自行节奏跑步机上跑步的小鼠中绘制大量CA1神经元内的细胞招募。我们发现，GABA能神经元，而不是他们的mesamatergic同行，优先招募自发发作间期活动在癫痫小鼠海马CA1区。虽然特定的细胞动力学发作间期尖峰被发现是高度可变的，他们始终与GABA能神经元的激活，导致在一个perisomatic抑制，减少神经元尖峰的主细胞层。考虑到GABA能神经元在正常认知功能期间塑造脑活动中的作用，它们在这些短暂事件期间的异常不平衡募集可能具有重要的下游效应，具有临床意义。
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.