Specific imbalance of excitatory/inhibitory signaling establishes seizure onset pattern in temporal lobe epilepsy
Specific imbalance of excitatory/inhibitory signaling establishes seizure onset pattern in temporal lobe epilepsy
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DOI：
10.1152/jn.01128.2015
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发表时间：
2016-06-01
影响因子：
2.5
通讯作者：
Williams, Sylvain
中科院分区：
文献类型：
--
作者：
Avoli, Massimo;de Curtis, Marco;Williams, Sylvain
低电压快速（LVF）和超同步（HYP）模式是中颞叶癫痫（MTLE）患者颅内脑电图记录中最常观察到的癫痫发作模式。这两种模式也发生在体内和体外的MTLE模型中，这些研究强调了不同的神经网络/神经递质受体信号在每种模式中的主要参与。首先，癫痫啮齿动物的lvf发作可起源于几个边缘结构，经常扩散，并与纹波带（80-200 Hz）的高频振荡有关，而HYP发作的癫痫发作始于海马，并倾向于保持以快速纹波（250-500 Hz）为主的局灶性。其次，来自边缘区主要细胞的体外细胞内记录表明，药物诱导的LVF发作的癫痫样放电是由同步抑制事件或超极化抑制性突触后电位屏障启动的；相反，HYP的发病与抑制的进行性损伤和伴随的无节制的兴奋增强有关。最后，体外光遗传学实验表明，在类似的实验条件下（即4-氨基吡啶应用），llf或hpp发作性癫痫的开始分别取决于神经元间网络或主细胞网络的主要参与。总的来说，这些数据可能为MTLE患者的治疗提供更好的治疗靶点，也可能为其他癫痫疾病患者提供更好的治疗靶点。
Lowvoltage fast (LVF) and hypersynchronous (HYP) patterns are the seizure-onset patterns most frequently observed in intracranial EEG recordings from mesial temporal lobe epilepsy (MTLE) patients. Both patterns also occur in models of MTLE in vivo and in vitro, and these studies have highlighted the predominant involvement of distinct neuronal network/neurotransmitter receptor signaling in each of them. First, LVF-onset seizures in epileptic rodents can originate from several limbic structures, frequently spread, and are associated with high-frequency oscillations in the ripple band (80-200 Hz), whereas HYP onset seizures initiate in the hippocampus and tend to remain focal with predominant fast ripples (250-500 Hz). Second, in vitro intracellular recordings from principal cells in limbic areas indicate that pharmacologically induced seizure-like discharges with LVF onset are initiated by a synchronous inhibitory event or by a hyperpolarizing inhibitory postsynaptic potential barrage; in contrast, HYP onset is associated with a progressive impairment of inhibition and concomitant unrestrained enhancement of excitation. Finally, in vitro optogenetic experiments show that, under comparable experimental conditions (i.e., 4-aminopyridine application), the initiation of LVF-or HYP-onset seizures depends on the preponderant involvement of interneuronal or principal cell networks, respectively. Overall, these data may provide insight to delineate better therapeutic targets in the treatment of patients presenting with MTLE and, perhaps, with other epileptic disorders as well.