Physiological unmasking of new glutamatergic pathways in the dentate gyrus of hippocampal slices from kainate-induced epileptic rats.
Physiological unmasking of new glutamatergic pathways in the dentate gyrus of hippocampal slices from kainate-induced epileptic rats.
复制标题
红藻氨酸诱导癫痫大鼠海马切片齿状回中新谷氨酸能通路的生理揭示。
DOI：
10.1152/jn.1998.79.1.418
复制
发表时间：
1998
影响因子：
2.5
通讯作者：
Dudek,FE
中科院分区：
文献类型：
--
作者：
Patrylo,PR;Dudek,FE
彼得·r·帕特里洛和f·爱德华·杜德克。癫痫大鼠海马齿状回新谷氨酸通路的生理揭示[j]。中国生物医学工程学报，2009,31(2):418-429。在颞叶癫痫患者和盐处理大鼠中，齿状颗粒细胞的苔藓状纤维将侧枝轴突送入内层分子层。先前对海碱处理大鼠的研究表明，当γ-氨基丁酸-a （GABAA）介导的抑制被双球茎碱阻断时，在苔藓纤维发芽的切片中偶尔会观察到异常的门门诱发事件。然而，这些异常并不常见，并且不清楚这些大鼠是否患有癫痫。Wuarin和Dudek报道，在海碱盐诱导的癫痫大鼠的切片中（治疗后3-13个月），门部刺激在大多数切片中引起异常事件，苔藓纤维发芽同时暴露于双藤碱和细胞外钾浓度升高[K+]o。使用相同的大鼠，从海马颗粒细胞切片中获得细胞外记录，以确定1)肝门刺激是否能在正常人工脑脊液（ACSF）中引起异常事件，2)仅添加双球茎碱可以掩盖肝门诱发的异常，谷氨酸受体拮抗剂可以阻断这些事件，3)仅增加[K+]可以掩盖这些异常。在正常ACSF中，27%的有发芽的切片与没有发芽的对照组（即盐处理或仅在盐酸盐处理后2-4天）相比，门部刺激引起了异常的场电位。在双球茎碱（10 μM）单独刺激下，84%的发芽切片的门部刺激触发了延长的场电位，而在两个对照组的切片中则没有。添加n -甲基-d-天冬氨酸（NMDA）受体拮抗剂dl-2-氨基-5-磷酸戊酸（AP5）可以阻断爆发或降低其发生的可能性。α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯(AMPA)/盐酸盐受体拮抗剂6,7-二硝基喹啉-2,3-二酮（DNQX）总能消除癫痫样发作。在盐处理的有发芽的大鼠中，而在盐处理的对照组中，6-9 mM也显示了异常的hila诱发反应[K+] 0。此外，在含有9 mm [K+]o的ACSF中，63%的发芽片产生持续1-40 s的自发爆发；在对照组中没有观察到类似的爆发。这些结果表明：1)苔藓纤维的发芽与新的谷氨酸能通路有关，尽管NMDA受体对这些通路的繁殖很重要，但AMPA受体的激活是至关重要的；2)[K+]o的适度升高，在一个对颗粒细胞影响相对较小的范围内，可以揭开这些新的兴奋回路并产生癫痫状爆发。3)当抑制被抑制或膜兴奋性增加时，这种新的电路是增加电图癫痫易感性的基础。
Patrylo, Peter R. and F. Edward Dudek.Physiological unmasking of new glutamatergic pathways in the dentate gyrus of hippocampal slices from kainate-induced epileptic rats.J. Neurophysiol.79: 418–429, 1998. In humans with temporal lobe epilepsy and kainate-treated rats, the mossy fibers of the dentate granule cells send collateral axons into the inner molecular layer. Prior investigations on kainate-treated rats demonstrated that abnormal hilar-evoked events can occasionally be observed in slices with mossy fiber sprouting when γ-aminobutyric acid-A (GABAA)–mediated inhibition is blocked with bicuculline. However, these abnormalities were observed infrequently, and it was unknown whether these rats were epileptic. Wuarin and Dudek reported that in slices from kainate-induced epileptic rats (3–13 mo after treatment), hilar stimulation evoked abnormal events in most slices with mossy fiber sprouting exposed simultaneously to bicuculline and elevated extracellular potassium concentration [K+]o. Using the same rats, extracellular recordings were obtained from granule cells in hippocampal slices to determine whether1) hilar stimulation could evoke abnormal events in slices with sprouting in normal artificial cerebrospinal fluid (ACSF),2) adding only bicuculline could unmask hilar-evoked abnormalities and glutamate-receptor antagonists could block these events, and3) increasing only [K+]ocould unmask these abnormalities. In normal ACSF, hilar stimulation evoked abnormal field potentials in 27% of slices with sprouting versus controls without sprouting (i.e., saline-treated or only 2–4 days after kainate treatment). In bicuculline (10 μM) alone, hilar stimulation triggered prolonged field potentials in 84% of slices with sprouting, but not in slices from the two control groups. Addition of theN-methyl-d-aspartate (NMDA) receptor antagonist,dl-2-amino-5-phosphonopentanoic acid (AP5), either blocked the bursts or reduced their probability of occurrence. The α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX), always eliminated the epileptiform bursts. In kainate-treated rats with sprouting, but not in saline-treated controls, abnormal hilar-evoked responses were also revealed in 6–9 mM [K+]o. Additionally, 63% of slices with sprouting generated spontaneous bursts lasting 1–40 s in ACSF containing 9 mm [K+]o; similar bursts were not observed in controls. These results indicate that1) mossy fiber sprouting is associated with new glutamatergic pathways, and although NMDA receptors are important for propagation through these circuits, AMPA receptor activation is crucial,2) modest elevations of [K+]o, in a range that would have relatively little effect on granule cells, can unmask these new excitatory circuits and generate epileptiform bursts, and3) this new circuitry underlies an increased electrographic seizure susceptibility when inhibition is depressed or membrane excitability is increased.