Department of Medical Neurobiology, IMRIC, Hebrew University-Hadassah School of Medicine, Jerusalem 91120, Israel.
Department of Medical Neurobiology, IMRIC, Hebrew University-Hadassah School of Medicine, Jerusalem 91120, Israel.
Neuroscience. 2017 Aug 15;357:325-337. doi: 10.1016/j.neuroscience.2017.06.013. Epub 2017 Jun 15.
In experimental models of temporal lobe epilepsy (TLE), brain neurons manifest multiple changes in intrinsic excitability that contribute to neuronal network hyperexcitability. We have investigated whether the intrinsic firing response gain, quantified by the slope of the function relating the number of evoked spikes (Ns) to input excitatory current intensity (I), is modified in principal rat hippocampal neurons in the pilocarpine-status epilepticus (SE) model of TLE.
Intracellular recordings were made in CA3 and CA1 pyramidal cells (PCs) and dentate granule cells (GCs) in acute hippocampal slices obtained 7-36days after pilocarpine-SE. Firing response gains were determined empirically from Ns/I relationships and compared to other measured neuronal properties.
The firing response gain in all three types of principal neurons, particularly in CA3 PCs, was markedly multiplied following pilocarpine-SE. Analyses of persistent changes in active and passive properties of CA3 PCs suggested that this increase is multifactorial in origin, the major factors being a reduction in amplitude of the slow afterhyperpolarization and an increase in the fraction of bursting neurons.
Here we show that pilocarpine-SE causes multiplication of the firing response gain in the three principal neurons in the hippocampal trisynaptic pathway. This alteration undoubtedly would contribute to hippocampal hyperexcitability in SE-induced TLE.
在颞叶癫痫（TLE）的实验模型中，大脑神经元表现出内在兴奋性的多种变化，这些变化有助于神经元网络的过度兴奋。我们研究了在匹罗卡品癫痫持续状态（SE）模型的大鼠海马神经元中，固有放电反应增益（通过将诱发的尖峰数（Ns）与兴奋性输入电流强度（I）的关系函数的斜率来量化）是否发生改变。
在急性海马切片中进行了 CA3 和 CA1 锥体神经元（PCs）和齿状回颗粒细胞（GCs）的细胞内记录，这些切片是在匹罗卡品-SE 后 7-36 天获得的。通过 Ns/I 关系经验性地确定放电反应增益，并与其他测量的神经元特性进行比较。
在所有三种主要神经元中，尤其是在 CA3 PCs 中，放电反应增益在匹罗卡品-SE 后显著增加。对 CA3 PCs 中活跃和被动特性的持续变化的分析表明，这种增加是多因素的，主要因素是慢后超极化幅度的降低和爆发神经元的比例增加。
在这里，我们显示匹罗卡品-SE 导致海马三突触通路中的三种主要神经元的放电反应增益增加。这种改变无疑会导致 SE 诱导的 TLE 中海马的过度兴奋。
