Stelzer A, Slater N T, ten Bruggencate G
Nature. 1987;326(6114):698-701. doi: 10.1038/326698a0.
The application of tetanic electrical stimuli to the stratum radiatum fibre pathway in the hippocampus in vitro produces an NMDA (N-methyl-D-aspartate) receptor-dependent enhancement of synaptic efficacy. Repeated application of such stimuli produces a progressive enhancement of synaptic efficacy leading to the genesis of spontaneous and stimulation-evoked epileptiform discharges. We have used this in vitro approach to explore the cellular mechanisms which underlie the kindling model of epilepsy. Kindling of the stratum radiatum fibre pathway in vitro induced a progressive, long-lasting reduction of both spontaneous and stimulation-evoked GABAergic (gamma-aminobutyric acid-mediated) inhibitory postsynaptic potentials (i.p.s.ps). The reduction of i.p.s.ps by kindling was associated with a profound decrease in the sensitivity of CA1 pyramidal neurons to ionophoretically applied GABA and an increase in sensitivity to NMDA. The reduction of i.p.s.ps and GABA sensitivity was prevented by kindling in the presence of the NMDA receptor antagonist D-2-amino-5-phosphonovalerate (D-APV). These results demonstrate that kindling-like stimulus patterns produce a reduction of GABAergic inhibition in the hippocampus resulting from a stimulus-induced postsynaptic activation of NMDA receptors. The modulation of GABAergic inhibition by NMDA receptors may cause the synaptic plasticity which underlies the kindling model of epilepsy.
在体外对海马体辐射层纤维通路施加强直电刺激会产生一种依赖N-甲基-D-天冬氨酸（NMDA）受体的突触效能增强。重复施加此类刺激会使突触效能逐渐增强，导致自发和刺激诱发的癫痫样放电的产生。我们利用这种体外方法来探索癫痫点燃模型背后的细胞机制。体外点燃辐射层纤维通路会导致自发和刺激诱发的γ-氨基丁酸（GABA）能抑制性突触后电位（i.p.s.ps）进行性、长期降低。点燃导致的i.p.s.ps降低与CA1锥体神经元对离子导入施加的GABA的敏感性显著降低以及对NMDA的敏感性增加有关。在NMDA受体拮抗剂D-2-氨基-5-磷酸戊酸（D-APV）存在的情况下进行点燃可防止i.p.s.ps和GABA敏感性的降低。这些结果表明，类似点燃的刺激模式会导致海马体中GABA能抑制的降低，这是由刺激诱导的NMDA受体突触后激活引起的。NMDA受体对GABA能抑制的调节可能会导致构成癫痫点燃模型基础的突触可塑性。
