Cell domain-dependent changes in the glutamatergic and GABAergic drives during epileptogenesis in the rat CA1 region
Cell domain-dependent changes in the glutamatergic and GABAergic drives during epileptogenesis in the rat CA1 region
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DOI：
10.1113/jphysiol.2006.119297
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发表时间：
2007-01-01
影响因子：
5.5
通讯作者：
Bernard, Christophe
中科院分区：
文献类型：
--
作者：
El-Hassar, Lynda;Milh, Mathieu;Bernard, Christophe
颞叶癫痫(TLE)慢性期的特点是谷氨酸能驱动与总的谷氨酸/GABA能驱动的比率增加，但目前尚不清楚这种修饰是否存在于癫痫阶段之前的潜伏期。利用匹罗卡品制作的大鼠TLE模型，我们报告了在潜伏期的早期(匹罗卡品后3-5天)，海马CA1区锥体细胞的这一比例降低。然而，在潜伏期的晚期(匹罗卡品后7-10天)，随着体内发作间歇性活动的发生，随着突触电流性质的依赖细胞区域的改变，它被增加。在潜伏期的晚期，体细胞的谷氨酸能驱动通过EPSC衰减时间常数的增加而增加，树突的谷氨酸驱动通过EPSC频率和幅度的增加而增加。GABA能驱动在胞体中没有变化，但在树突中减少，这是因为IPSC频率的下降比IPSC动力学的增加更明显。理论上的考虑表明，这些修饰足以产生发作间歇性活动。在癫痫动物中，谷氨酸能驱动与整个突触驱动的比率没有进一步改变，尽管突触电流频率和动力学发生了额外的变化。这些结果表明，在癫痫慢性期之前，CA1区谷氨酸能增加而GABA能减少的整体变化，可能有助于发作间期活动的发生和/或传播。
An increased ratio of the glutamatergic drive to the overall glutamatergic/GABAergic drive characterizes the chronic stage of temporal lobe epilepsy (TLE), but it is unclear whether this modification is present during the latent period that often precedes the epileptic stage. Using the pilocarpine model of TLE in rats, we report that this ratio is decreased in hippocampal CA1 pyramidal cells during the early phase of the latent period (3-5 days post pilocarpine). It is, however, increased during the late phase of the latent period (7-10 days post pilocarpine), via cell domain-dependent alterations in synaptic current properties, concomitant with the occurrence of interictal-like activity in vivo. During the late latent period, the glutamatergic drive was increased in somata via an enhancement in EPSC decay time constant and in dendrites via an increase in EPSC frequency and amplitude. The GABAergic drive remained unchanged in the soma but was decreased in dendrites, since the drop off in IPSC frequency was more marked than the increase in IPSC kinetics. Theoretical considerations suggest that these modifications are sufficient to produce interictal-like activity. In epileptic animals, the ratio of the glutamatergic drive to the overall synaptic drive was not further modified, despite additional changes in synaptic current frequency and kinetics. These results show that the global changes to more glutamatergic and less GABAergic activities in the CA1 region precede the chronic stage of epilepsy, possibly facilitating the occurrence and/or the propagation of interictal activity.