Epilepsie de l'Enfant et Plasticité Cérébrale, INSERM U 663, Paris, France.
Brain Res. 2013 Aug 7;1525:39-52. doi: 10.1016/j.brainres.2013.05.044. Epub 2013 Jun 3.
Electroencephalographic generalized spike and wave discharges (SWD), the hallmark of human absence seizures, are generated in thalamocortical networks. However, the potential alterations in these networks in terms of the efficacy of the reciprocal synaptic activities between the cortex and the thalamus are not known in this pathology. Here, the efficacy of these reciprocal connections is assessed in vitro in thalamocortical slices obtained from BS/Orl mice, which is a new genetic model of absence epilepsy. These mice show spontaneous SWD, and their features can be compared to that of BR/Orl mice, which are free of SWD. In addition, since gap junctions may modulate the efficacy of these connections, their implications in pharmacologically-induced epileptiform discharges were studied in the same slices. The thalamus and neocortex were independently stimulated and the electrically-evoked responses in both structures were recorded from the same slice. The synaptic efficacy of thalamocortical and corticothalamic connections were assessed by measuring the dynamic range of synaptic field potential changes in response to increasing stimulation strengths. The connection efficacy was weaker in epileptic mice however, this decrease in efficacy was more pronounced in thalamocortical afferents, thus introducing an imbalance in the reciprocal connections between the cortex and thalamus. However, short-term facilitation of the thalamocortical responses were increased in epileptic mice compared to non-epileptic animals. These features may favor occurrence of rhythmical activities in thalamocortical networks. In addition, carbenoxolone (a gap junction blocker) decreased the cumulative duration of 4-aminopyridine-induced ictal-like activities, with a slower time course in epileptic mice. However, the 4-aminopyridine-induced GABA-dependent negative potentials, which appeared to trigger the ictal-like activities, remained. Our results show that the balance of the reciprocal connections between the thalamus and cortex is altered in favor of the corticothalamic connections in epileptic mice, and suggest that gap junctions mediate a stronger cortical synchronization in this strain.
脑电图广泛棘波和尖波放电（SWD）是人类失神发作的标志，是在丘脑皮质网络中产生的。然而，在这种病理状态下，皮质和丘脑之间的相互突触活动的效力在这些网络中的潜在变化尚不清楚。在这里，我们在从 BS/Orl 小鼠获得的丘脑皮质切片中评估了这些相互连接的效力，BS/Orl 小鼠是一种新的失神癫痫遗传模型。这些小鼠表现出自发性 SWD，它们的特征可以与没有 SWD 的 BR/Orl 小鼠进行比较。此外，由于缝隙连接可能调节这些连接的效力，我们在相同的切片中研究了它们在药理学诱导的癫痫样放电中的影响。独立刺激丘脑和新皮层，并从同一切片中记录两个结构中的电诱发反应。通过测量响应增加刺激强度时突触场电位变化的动态范围来评估丘脑皮质和皮质丘脑连接的突触效力。然而，在癫痫小鼠中，连接效力较弱，但是这种效力的降低在丘脑皮质传入中更为明显，从而在皮质和丘脑之间的相互连接中引入了不平衡。然而，与非癫痫动物相比，癫痫小鼠的丘脑皮质反应的短期易化增加。这些特征可能有利于丘脑皮质网络中节律性活动的发生。此外，Carbenoxolone（缝隙连接阻断剂）降低了 4-氨基吡啶诱导的类似癫痫发作活动的累积持续时间，在癫痫小鼠中具有更慢的时间过程。然而，4-氨基吡啶诱导的 GABA 依赖性负电位仍然存在，这些负电位似乎触发了类似癫痫发作的活动。我们的研究结果表明，在癫痫小鼠中，丘脑和皮质之间的相互连接的平衡发生了变化，有利于皮质丘脑连接，并且表明缝隙连接在这种品系中介导了更强的皮质同步。
