Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Canada.
Hippocampus. 2011 Jul;21(7):702-13. doi: 10.1002/hipo.20785. Epub 2010 Apr 13.
The perirhinal cortex (PC), which is heavily connected with several epileptogenic regions of the limbic system such as the entorhinal cortex and amygdala, is involved in the generation and spread of seizures. However, the functional alterations occurring within an epileptic PC network are unknown. Here, we analyzed this issue by using in vitro electrophysiology and immunohistochemistry in brain tissue obtained from pilocarpine-treated epileptic rats and age-matched, nonepileptic controls (NECs). Neurons recorded intracellularly from the PC deep layers in the two experimental groups had similar intrinsic and firing properties and generated spontaneous depolarizing and hyperpolarizing postsynaptic potentials with comparable duration and amplitude. However, spontaneous and stimulus-induced epileptiform discharges were seen with field potential recordings in over one-fifth of pilocarpine-treated slices but never in NEC tissue. These network events were reduced in duration by antagonizing NMDA receptors and abolished by NMDA + non-NMDA glutamatergic receptor antagonists. Pharmacologically isolated isolated inhibitory postsynaptic potentials had reversal potentials for the early GABA(A) receptor-mediated component that were significantly more depolarized in pilocarpine-treated cells. Experiments with a potassium-chloride cotransporter 2 antibody identified, in pilocarpine-treated PC, a significant immunostaining decrease that could not be explained by neuronal loss. However, interneurons expressing parvalbumin and neuropeptide Y were found to be decreased throughout the PC, whereas cholecystokinin-positive cells were diminished in superficial layers. These findings demonstrate synaptic hyperexcitability that is contributed by attenuated inhibition in the PC of pilocarpine-treated epileptic rats and underscore the role of PC networks in temporal lobe epilepsy.
内嗅皮质（PC）与边缘系统的多个致痫区域如内嗅皮层和杏仁核紧密相连，参与癫痫发作的产生和扩散。然而，癫痫性PC网络内发生的功能改变尚不清楚。在此，我们通过对毛果芸香碱处理的癫痫大鼠及年龄匹配的非癫痫对照（NEC）脑组织进行体外电生理学和免疫组织化学分析来探讨这一问题。在两个实验组中，从PC深层细胞内记录的神经元具有相似的内在特性和放电特性，并产生持续时间和幅度相当的自发性去极化和超极化突触后电位。然而，在超过五分之一的毛果芸香碱处理切片中通过场电位记录观察到自发性和刺激诱导的癫痫样放电，而在NEC组织中从未观察到。通过拮抗NMDA受体可缩短这些网络事件的持续时间，而NMDA +非NMDA谷氨酸能受体拮抗剂可消除这些事件。药理学分离的抑制性突触后电位对早期GABA(A)受体介导成分的反转电位在毛果芸香碱处理的细胞中明显更去极化。用氯化钾共转运体2抗体进行的实验发现，在毛果芸香碱处理的PC中，免疫染色显著降低，这不能用神经元丢失来解释。然而，发现整个PC中表达小白蛋白和神经肽Y的中间神经元减少，而胆囊收缩素阳性细胞在表层减少。这些发现表明，在毛果芸香碱处理的癫痫大鼠的PC中，抑制减弱导致突触兴奋性过高，并强调了PC网络在颞叶癫痫中的作用。
