Pinault Didier, O'Brien Terence J
Physiopathologie clinique et expérimentale de la schizophrénie INSERM : U666 IFR37 Université Louis Pasteur - Strasbourg I FR.
Thalamus Relat Syst. 2005;3(3):181-203. doi: 10.1017/S1472928807000209. Epub 2007 Jan 22.
The absence epilepsies are characterized by recurrent episodes of loss of consciousness associated with generalized spike-and-wave discharges, with an abrupt onset and offset, in the thalamocortical system. In the absence of detailed neurophysiological studies in humans, many of the concepts regarding the pathophysiological basis of absence seizures are based on studies in animal models. Each of these models has its particular strengths and limitations, and the validity of findings from these models for the human condition cannot be assumed. Consequently, studies in different models have produced some conflicting findings and conclusions. A long-standing concept, based primarily from studies in vivo in cats and in vitro brain slices, is that these paroxysmal electrical events develop suddenly from sleep-related spindle oscillations. More specifically, it is proposed that the initial mechanisms that underlie absence-related spike-and-wave discharges are located in the thalamus, involving especially the thalamic reticular nucleus. By contrast, more recent studies in well-established, genetic models of absence epilepsy in rats demonstrate that spike-and-wave discharges originate in a cortical focus and develop from a wake-related natural corticothalamic sensorimotor rhythm. In this review we integrate recent findings showing that, in both the thalamus and the neocortex, genetically-determined, absence-related spike-and-wave discharges are the manifestation of hypersynchronized, cellular, rhythmic excitations and inhibitions that result from a combination of complex, intrinsic, synaptic mechanisms. Arguments are put forward supporting the hypothesis that layer VI corticothalamic neurons act as 'drivers' in the generation of spike-and-wave discharges in the somatosensory thalamocortical system that result in corticothalamic resonances particularly initially involving the thalamic reticular nucleus. However an important unresolved question is: what are the cellular and network mechanisms responsible for the switch from physiological, wake-related, natural oscillations into pathological spike-and-wave discharges? We speculate on possible answers to this, building particularly on recent findings from genetic models in rats.
失神癫痫的特征是与全脑棘慢波放电相关的反复意识丧失发作，发作和终止均突然，发生于丘脑皮质系统。由于缺乏对人类的详细神经生理学研究，许多关于失神发作病理生理基础的概念都基于动物模型研究。这些模型各有其独特的优势和局限性，不能假定这些模型的研究结果对人类情况具有有效性。因此，不同模型的研究产生了一些相互矛盾的结果和结论。一个长期存在的概念主要基于对猫的体内研究和体外脑片研究，即这些阵发性电活动突然从与睡眠相关的纺锤波振荡发展而来。更具体地说，有人提出，与失神相关的棘慢波放电的初始机制位于丘脑，尤其涉及丘脑网状核。相比之下，最近对已确立的大鼠失神癫痫遗传模型的研究表明，棘慢波放电起源于皮质病灶，并从与清醒相关的自然皮质丘脑感觉运动节律发展而来。在这篇综述中，我们整合了最近的研究结果，表明在丘脑和新皮质中，基因决定的、与失神相关的棘慢波放电是由复杂的内在突触机制组合导致的超同步细胞节律性兴奋和抑制的表现。有人提出论据支持这样的假设，即VI层皮质丘脑神经元在体感丘脑皮质系统棘慢波放电的产生中充当“驱动者”，导致皮质丘脑共振，特别是最初涉及丘脑网状核。然而，一个重要的未解决问题是：从生理的、与清醒相关的自然振荡转变为病理性棘慢波放电的细胞和网络机制是什么？我们特别基于大鼠遗传模型的最新研究结果推测可能的答案。
