Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS (IEPhB), 44, Toreza prospekt, Saint Petersburg 194223, Russia; Ioffe Institute, 26, Politekhnicheskaya, St Petersburg 194021, Russia.
Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS (IEPhB), 44, Toreza prospekt, Saint Petersburg 194223, Russia.
Neuroscience. 2018 May 21;379:202-215. doi: 10.1016/j.neuroscience.2018.03.020. Epub 2018 Mar 24.
Profound alterations in both the synaptic and intrinsic membrane properties of neurons that increase the neuronal network excitability are found in epileptic tissue. However, there are still uncertainties regarding the kind of changes in the intrinsic membrane properties occurring during epileptogenesis. Epileptogenesis is typically triggered by the initial brain-damaging insult, and status epilepticus (SE) is one of such insults. In the present study, we explored the acute changes in the intrinsic membrane properties of pyramidal cells one day after SE in a rat lithium-pilocarpine model. Using whole-cell patch-clamp recording and the dynamic-clamp technique, we investigated the properties of regular-spiking neurons in the entorhinal cortex (EC) and the medial prefrontal cortex (PFC), two areas differentially affected by SE. We found that one day after SE: (1) the intrinsic membrane properties of EC neurons are significantly altered, while the properties of PFC neurons are mostly unchanged; (2) the input resistance and membrane time constant of regular-spiking neurons are reduced due to enhanced leak current; (3) the active membrane properties of neurons are mostly unaffected; and (4) changes in the passive membrane properties diminish the intrinsic neuronal excitability. Therefore, our results suggest that the acute changes in the intrinsic membrane properties of entorhinal neurons following pilocarpine-induced SE do not contribute to network hyperexcitability. In contrast, at the early stage of epileptogenesis, protective homeostatic plasticity of intrinsic membrane properties is observed in the EC; it reduces the neuronal excitability in response to increased network excitability.
在癫痫组织中发现，神经元的突触和内在膜特性发生深刻改变，从而增加神经元网络的兴奋性。然而，在癫痫发生过程中内在膜特性发生的变化类型仍存在不确定性。癫痫发生通常由最初的脑损伤性刺激引发，癫痫持续状态（SE）就是其中一种刺激。在本研究中，我们在锂匹鲁卡品大鼠模型中探索了 SE 后一天内在海马区（EC）和前额叶皮质（PFC）中锥体神经元内在膜特性的急性变化。使用全细胞膜片钳记录和动态箝位技术，我们研究了 SE 不同影响的两个区域即内嗅皮层（EC）和前额叶皮质（PFC）中规则放电神经元的特性。我们发现 SE 后一天：（1）EC 神经元的内在膜特性发生显著改变，而 PFC 神经元的特性大多不变；（2）由于增强的漏电流，规则放电神经元的输入电阻和膜时间常数降低；（3）神经元的主动膜特性基本不受影响；（4）被动膜特性的变化降低了内在神经元的兴奋性。因此，我们的结果表明，匹鲁卡品诱导 SE 后海马区神经元内在膜特性的急性变化不会导致网络过度兴奋。相反，在癫痫发生的早期阶段，EC 中观察到内在膜特性的保护性同型可塑性；它降低了神经元的兴奋性，以响应增加的网络兴奋性。
