Perirhinal Cortex Hyperexcitability in Pilocarpine-Treated Epileptic Rats
Perirhinal Cortex Hyperexcitability in Pilocarpine-Treated Epileptic Rats
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DOI：
10.1002/hipo.20785
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发表时间：
2011-07-01
期刊：
影响因子：
3.5
通讯作者：
Avoli, Massimo
中科院分区：
文献类型：
--
作者：
Benini, Ruba;Longo, Daniela;Avoli, Massimo
嗅周皮质(PC)与内嗅皮质、杏仁核等边缘系统致痫区域紧密相连，参与癫痫的发生和扩散。然而，癫痫PC网络中发生的功能改变尚不清楚。在这里，我们使用体外电生理学和免疫组织化学的方法，从匹罗卡品治疗的癫痫大鼠和年龄匹配的非癫痫对照组(NECS)的脑组织中分析了这一问题。两个实验组在PC深层细胞内记录的神经元具有相似的本征和放电特性，并产生时程和幅度相当的自发去极化和超极化突触后电位。然而，在超过五分之一的匹罗卡品治疗的脑片中，可以看到自发的和刺激诱导的癫痫样放电，但在NEC组织中却没有。NMDA受体拮抗剂可缩短这些网络事件的持续时间，NMDA1非NMDA谷氨酸能受体拮抗剂可使其消失。从药物上分离的分离的抑制性突触后电位对早期GABAA受体介导的成分具有逆转潜力，在匹罗卡品处理的细胞中，这种成分的去极化程度明显更高。使用氯化钾转运蛋白2抗体的实验证明，在匹罗卡品治疗的PC中，免疫染色显著减少，这不能用神经元丢失来解释。然而，表达小白蛋白和神经肽Y的中间神经元在整个PC层都减少了，而浅层的CCK阳性细胞也减少了。这些发现证明了由匹罗卡品治疗的癫痫大鼠PC中减弱的抑制所致的突触过度兴奋性，并强调了PC网络在颞叶癫痫中的作用。(C)2010年Wiley-Liss公司
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 1 non-NMDA glutamatergic receptor antagonists. Pharmacologically isolated isolated inhibitory postsynaptic potentials had reversal potentials for the early GABAA 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. (C) 2010 Wiley-Liss, Inc.