Henan Neurodevelopment Engineering Research Center for Children, Henan Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, 33 Longhu Outer Circle Dong Road, Zhengzhou, 450018, Henan, China.
Henan Neurodevelopment Engineering Research Center for Children, Henan Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, 33 Longhu Outer Circle Dong Road, Zhengzhou, 450018, Henan, China.
Brain Res. 2021 Aug 1;1764:147467. doi: 10.1016/j.brainres.2021.147467. Epub 2021 Apr 5.
Excitation-inhibition imbalance of GABAergic interneurons is predisposed to develop chronic temporal lobe epilepsy (TLE). We have previously shown that virtually every neuronal nitric oxide synthase (nNOS)-positive cell is a GABAergic inhibitory interneuron in the denate gyrus. The present study was designed to quantify the number of nNOS-containing hilar interneurons using stereology in pilocapine- and kainic acid (KA)-exposed transgenic adult mice that expressed GFP under the nNOS promoter. In addition, we studied the properties of miniature excitatory postsynaptic current (mEPSC) and paired-pulse response ratio (PPR) of evoked EPSC in nNOS interneurons using whole cell recording techniques. Results showed that there were fewer nNOS-immunoreactive interneurons of chronically epileptic animals. Importantly, patch-clamp recordings revealed reduction in mEPSC frequency, indicating diminished global excitatory input. In contrast, PPR of evoked EPSC following the granule cell layer stimulation was increased in epileptic animals suggesting reduced neurotransmitter release from granule cell input. In summary, we propose that impaired excitatory drive onto hippocampal nNOS interneurons may be implicated in the development of refractory epilepsy.
GABA 能中间神经元的兴奋抑制失衡易导致慢性颞叶癫痫（TLE）的发生。我们先前已经证实，在齿状回中，几乎所有神经元型一氧化氮合酶（nNOS）阳性细胞都是 GABA 能抑制性中间神经元。本研究旨在通过立体学方法，对表达 nNOS 启动子下 GFP 的毛果芸香碱和海人酸（KA）暴露转基因成年小鼠中的 nNOS 阳性海马回神经元进行定量计数。此外，我们还使用全细胞膜片钳记录技术，研究了 nNOS 中间神经元诱发的兴奋性突触后电流（EPSC）的微小兴奋性突触后电流（mEPSC）和成对脉冲反应比（PPR）的特性。结果表明，慢性癫痫动物的 nNOS 免疫反应性中间神经元数量较少。重要的是，膜片钳记录显示 mEPSC 频率降低，表明整体兴奋性输入减少。相比之下，癫痫动物颗粒细胞层刺激后诱发的 EPSC 的 PPR 增加，表明颗粒细胞输入的神经递质释放减少。综上所述，我们提出，海马 nNOS 中间神经元兴奋性传入受损可能与难治性癫痫的发生有关。
