Chung Sungkwon, Spruston Nelson, Koh Sookyong
Department of Physiology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, South Korea.
Scientific Program, Janelia Research Campus, Ashburn, Virginia, United States of America.
PLoS One. 2015 Mar 16;10(3):e0119411. doi: 10.1371/journal.pone.0119411. eCollection 2015.
Kainic acid-induced status epilepticus (KA-SE) in mature rats results in the development of spontaneous recurrent seizures and a pattern of cell death resembling hippocampal sclerosis in patients with temporal lobe epilepsy. In contrast, KA-SE in young animals before postnatal day (P) 18 is less likely to cause cell death or epilepsy. To investigate whether changes in neuronal excitability occur in the subiculum after KA-SE, we examined the age-dependent effects of SE on the bursting neurons of subiculum, the major output region of the hippocampus. Patch-clamp recordings were used to monitor bursting in pyramidal neurons in the subiculum of rat hippocampal slices. Neurons were studied either one or 2-3 weeks following injection of KA or saline (control) in immature (P15) or more mature (P30) rats, which differ in their sensitivity to KA as well as the long-term sequelae of the KA-SE. A significantly greater proportion of subicular pyramidal neurons from P15 rats were strong-bursting neurons and showed increased frequency-dependent bursting compared to P30 animals. Frequency-dependent burst firing was enhanced in P30, but not in P15 rats following KA-SE. The enhancement of bursting induced by KA-SE in more mature rats suggests that the frequency-dependent limitation of repetitive burst firing, which normally occurs in the subiculum, is compromised following SE. These changes could facilitate the initiation of spontaneous recurrent seizures or their spread from the hippocampus to other parts of the brain.
成年大鼠中,海人酸诱导的癫痫持续状态(KA-SE)会导致自发性反复癫痫发作的发生,以及一种类似于颞叶癫痫患者海马硬化的细胞死亡模式。相比之下,出生后第18天(P18)之前的幼龄动物发生KA-SE后,引起细胞死亡或癫痫的可能性较小。为了研究KA-SE后海马下托神经元兴奋性是否发生变化,我们研究了癫痫持续状态对海马下托(海马的主要输出区域)爆发性神经元的年龄依赖性影响。采用膜片钳记录技术监测大鼠海马脑片海马下托锥体神经元的爆发活动。在未成熟(P15)或更成熟(P30)的大鼠中注射KA或生理盐水(对照)后1周或2 - 3周对神经元进行研究,这两组大鼠对KA的敏感性以及KA-SE的长期后遗症有所不同。与P30大鼠相比,P15大鼠海马下托锥体神经元中强爆发性神经元的比例显著更高,且频率依赖性爆发增加。KA-SE后,P30大鼠的频率依赖性爆发放电增强,但P15大鼠未增强。KA-SE在更成熟大鼠中诱导的爆发增强表明,正常情况下发生在海马下托的重复性爆发放电的频率依赖性限制在癫痫持续状态后受到损害。这些变化可能会促进自发性反复癫痫发作的起始或从海马向脑的其他部位扩散。