Pathological high frequency oscillations associate with increased GABA synaptic activity in pediatric epilepsy surgery patients
Pathological high frequency oscillations associate with increased GABA synaptic activity in pediatric epilepsy surgery patients
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DOI：
10.1016/j.nbd.2019.104618
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发表时间：
2020-02-01
影响因子：
6.1
通讯作者：
Wu, Joyce Y.
中科院分区：
文献类型：
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作者：
Cepeda, Carlos;Levinson, Simon;Wu, Joyce Y.
病理性高频振荡（HFO），特别是快波（FR，> 250 Hz），是活动性致痫区的特征性表现。然而，FR的起源仍然未知。在这里，我们探讨了术中切除前皮质电图（ECoG）记录的FR与从切除用于治疗耐药性癫痫的皮质组织样本中离体记录的自发性突触活动之间的相关性。该队列包括47名患有局灶性皮质发育不良（CD I型和II型）、结节性硬化症（TSC）和非CD病理的儿童（年龄0.22-9.99岁）。全细胞膜片钳记录从皮质区域的锥体神经元和中间神经元获得，其对于病理性HFO是阳性或阴性的，定义为ECoG处的FR带振荡（250-500 Hz）。在HFO +和HFO-区域之间比较自发兴奋性和抑制性突触后电流（分别为sEPSC和IPSC）的频率。无论病理底物，与FR阴性的区域相比，FR阳性的区域显示sIPSC的频率显著增加。相比之下，sEPSC的频率在两个地区是相似的。在约三分之一的病例（n = 17）中，观察到起搏GABA突触活动（PGA）。在绝大多数（n = 15）中，PGA发生在HFO +区域。此外，快速尖峰的中间神经元仅在HFO +区域显示出过度兴奋的迹象。这些结果表明，在儿童癫痫患者中，GABA突触活性增加与致痫区的发作间期FR相关，并表明GABA能中间神经元在病理性HFO的产生中发挥积极作用。GABA突触活动的增加可以抑制致痫区皮质锥体神经元的过度兴奋，但也可以促进神经元网络的同步性。
Pathological high-frequency oscillations (HFOs), specifically fast ripples (FRs, > 250 Hz), are pathognomonic of an active epileptogenic zone. However, the origin of FRs remains unknown. Here we explored the correlation between FRs recorded with intraoperative pre-resection electrocorticography (ECoG) and spontaneous synaptic activity recorded ex vivo from cortical tissue samples resected for the treatment of pharmacoresistant epilepsy. The cohort included 47 children (ages 0.22-9.99 yr) with focal cortical dysplasias (CD types I and II), tuberous sclerosis complex (TSC) and non-CD pathologies. Whole-cell patch clamp recordings were obtained from pyramidal neurons and interneurons in cortical regions that were positive or negative for pathological HFOs, defined as FR band oscillations (250-500 Hz) at ECoG. The frequency of spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and IPSCs, respectively) was compared between HFO + and HFO- regions. Regardless of pathological substrate, regions positive for FRs displayed significantly increased frequencies of sIPSCs compared with regions negative for FRs. In contrast, the frequency of sEPSCs was similar in both regions. In about one third of cases (n = 17), pacemaker GABA synaptic activity (PGA) was observed. In the vast majority (n = 15), PGA occurred in HFO + areas. Further, fast-spiking interneurons displayed signs of hyperexcitability exclusively in HFO + areas. These results indicate that, in pediatric epilepsy patients, increased GABA synaptic activity is associated with interictal FRs in the epileptogenic zone and suggest an active role of GABAergic interneurons in the generation of pathological HFOs. Increased GABA synaptic activity could serve to dampen excessive excitability of cortical pyramidal neurons in the epileptogenic zone, but it could also promote neuronal network synchrony.