Xiang Hui, Chen Huan-Xin, Yu Xin-Xin, King Michael A, Roper Steven N
Department of Neurological Surgery and McKnight Brain Institute, University of Florida College of Medicine, Gainesville, USA.
J Neurophysiol. 2006 Aug;96(2):569-78. doi: 10.1152/jn.01133.2005. Epub 2006 Apr 26.
Cortical dysplasia (CD) is strongly associated with epilepsy. Enhanced excitability in dysplastic neuronal networks is believed to contribute to epileptogenesis, but the underlying mechanisms for the hyperexcitability are poorly understood. Cortical GABAergic interneurons provide the principal inhibition in the neuronal networks by forming inhibitory synapses on excitatory neurons. The aim of the present study was to determine if the function of interneurons in CD is compromised. In a rat model of CD, in utero irradiation, we studied spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs) in cortical interneurons using whole cell recording techniques. Two types of interneurons, type I and type II, were identified based on their distinctive spike patterns and short-term synaptic plasticity. We found that the frequencies of sEPSCs and mEPSCs were significantly decreased in both types of interneurons in CD. However, the amplitude and kinetics of sEPSCs and mEPSCs were not different. Five-pulse, 20-Hz stimulation produced short-term depression in type I interneurons in both CD and control tissue. Type II interneurons showed a robust short-term facilitation in both CD and control tissue. Morphological analysis of biocytin-filled neurons revealed that dendritic trees of both types of interneurons were not altered in CD. Our results demonstrate that the excitatory drive, namely sEPSCs and mEPSCs, in two main types of interneuron is largely attenuated in CD, probably due to a reduction in the number of excitatory synapses on both types of interneurons in CD.
皮质发育异常（CD）与癫痫密切相关。发育异常的神经元网络中兴奋性增强被认为与癫痫发生有关，但这种过度兴奋性的潜在机制尚不清楚。皮质GABA能中间神经元通过在兴奋性神经元上形成抑制性突触，在神经元网络中提供主要抑制作用。本研究的目的是确定CD中中间神经元的功能是否受损。在子宫内照射诱导的CD大鼠模型中，我们使用全细胞记录技术研究了皮质中间神经元的自发性和微小兴奋性突触后电流（sEPSCs和mEPSCs）。根据其独特的放电模式和短期突触可塑性，鉴定出两种类型的中间神经元，I型和II型。我们发现，CD中两种类型的中间神经元的sEPSCs和mEPSCs频率均显著降低。然而，sEPSCs和mEPSCs的幅度和动力学没有差异。五脉冲、20赫兹刺激在CD和对照组织的I型中间神经元中均产生短期抑制。II型中间神经元在CD和对照组织中均表现出强烈的短期易化。对生物素填充神经元的形态学分析表明，CD中两种类型的中间神经元的树突分支均未改变。我们的结果表明，在CD中，两种主要类型的中间神经元的兴奋性驱动，即sEPSCs和mEPSCs，在很大程度上减弱，这可能是由于CD中两种类型的中间神经元上兴奋性突触数量减少所致。
