Intrinsic neurophysiological properties of hilar ectopic and normotopic dentate granule cells in human temporal lobe epilepsy and a rat model
Intrinsic neurophysiological properties of hilar ectopic and normotopic dentate granule cells in human temporal lobe epilepsy and a rat model
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DOI：
10.1152/jn.00835.2014
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发表时间：
2015-02-15
影响因子：
2.5
通讯作者：
Murphy, G. G.
中科院分区：
文献类型：
--
作者：
Althaus, A. L.;Sagher, O.;Murphy, G. G.
在人类颞叶癫痫(TLE)和大多数啮齿动物模型中，肺门异位齿状颗粒细胞(DGC)是异常可塑性的显著特征。最近来自啮齿动物TLE模型的证据表明，肺门异位DGC有助于癫痫海马网内的过度兴奋。在这里，我们研究了来自人类TLE和大鼠毛果芸香碱TLE模型的DGCs的内在兴奋性，目的是比较肺门异位DGCs与正常的颗粒细胞层(GCL)对应的DGCs的神经生理学。我们从人TLE组织中记录了36个GCL和7个肺门部DGC。与GCL DGCs相比，患者组织中的肺门DGCs表现出较低的动作电位(AP)放电频率，较高的AP去极化阈值，且单个AP波形不同，与兴奋性的整体下降一致。为了评价肝门部异位DGC的内在神经生理学，我们在匹罗卡品诱导的癫痫持续状态或假治疗后2-4个月记录了逆转录病毒出生的成年DGC。癫痫大鼠肺门DGCs的AP放电频率高于正常对照组和癫痫大鼠DGCs。他们还表现出更多的去极化静息膜电位和更宽的AP波形，表明整体兴奋性增加。疾病和疾病模型之间的对比发现可能反映了从人类手术标本中获得的晚期疾病组织与在大鼠TLE模型中检查的早期疾病组织之间的差异。这些数据代表了来自人类海马区的异位树突状细胞和在啮齿动物TLE模型中预期出生的异位树突状细胞的首次神经生理学特征。
Hilar ectopic dentate granule cells (DGCs) are a salient feature of aberrant plasticity in human temporal lobe epilepsy (TLE) and most rodent models of the disease. Recent evidence from rodent TLE models suggests that hilar ectopic DGCs contribute to hyperexcitability within the epileptic hippocampal network. Here we investigate the intrinsic excitability of DGCs from humans with TLE and the rat pilocarpine TLE model with the objective of comparing the neurophysiology of hilar ectopic DGCs to their normotopic counterparts in the granule cell layer (GCL). We recorded from 36 GCL and 7 hilar DGCs from human TLE tissue. Compared with GCL DGCs, hilar DGCs in patient tissue exhibited lower action potential (AP) firing rates, more depolarized AP threshold, and differed in single AP waveform, consistent with an overall decrease in excitability. To evaluate the intrinsic neurophysiology of hilar ectopic DGCs, we made recordings from retrovirus-birthdated, adult-born DGCs 2-4 mo after pilocarpine-induced status epilepticus or sham treatment in rats. Hilar DGCs from epileptic rats exhibited higher AP firing rates than normotopic DGCs from epileptic or control animals. They also displayed more depolarized resting membrane potential and wider AP waveforms, indicating an overall increase in excitability. The contrasting findings between disease and disease model may reflect differences between the late-stage disease tissue available from human surgical specimens and the earlier disease stage examined in the rat TLE model. These data represent the first neurophysiological characterization of ectopic DGCs from human hippocampus and prospectively birthdated ectopic DGCs in a rodent TLE model.