Schneiderman J H
Wellesley Hospital, Toronto, Ontario, Canada.
Neuroscience. 1997 Dec;81(4):1111-22. doi: 10.1016/s0306-4522(97)00209-1.
Persistent hyperexcitability follows synchronized bursting induced in the CA3 region of hippocampal slices by perfusion with high concentrations (2000 IU/ml) of the GABAA antagonist, penicillin. This hyperexcitable state is characterized by: i) slow recovery from bursting following penicillin washout; ii) persistent "post-burst" field potential oscillations and iii) increased probability of spontaneous bursting with ordinarily sub-convulsant doses of GABAA antagonists. An N-methyl-D-aspartate-independent type of long-term potentiation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate excitatory postsynaptic potentials occurred following bursting. However, similar increases in excitatory postsynaptic potential magnitude also occurred after a subconvulsant dose of penicillin (500 IU/ml) which did not produce the other features of persistent hyperexcitability. Furthermore, long-term potentiation either increased or remained stable after bursting stopped, whereas, post-burst oscillations gradually diminished with time. Low doses of the AMPA/kainate antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, which restored the potentiated excitatory postsynaptic potentials to control levels, reduced but did not eliminate the post-burst oscillation. Tetanus-induced long-term potentiation did not reproduce the hyperexcitable state seen after bursting. These findings indicate that the epileptiform bursting caused by blocking GABAA-mediated inhibition induces long-term potentiation which is partially responsible for persistent burst-induced hyperexcitability but is not sufficient to entirely explain it. The hippocampus which is critical for normal memory is also frequently the generator of intractable epileptic seizures. Seizure-like discharges in the hippocampus induced long-lasting increases in synaptic efficacy similar to those thought to underlie normal memory. This form of long-term potentiation contributed to the network oscillations characteristics of the hyperexcitable state persisting after epileptiform activity but was not sufficient to entirely explain them. Epileptic seizures may engage normal memory mechanisms which increase neuronal excitability and predispose the hippocampal network to further seizures. This may, in part, account for the propensity for hippocampal seizure foci to become intractable.
用高浓度（2000国际单位/毫升）的GABAA拮抗剂青霉素灌注海马切片的CA3区所诱导的同步爆发之后，会出现持续性的过度兴奋。这种过度兴奋状态的特征为：i）青霉素洗脱后爆发的恢复缓慢；ii）持续性的“爆发后”场电位振荡；iii）使用通常低于惊厥剂量的GABAA拮抗剂时，自发爆发的概率增加。爆发后出现了一种不依赖N-甲基-D-天冬氨酸的α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）/海人藻酸兴奋性突触后电位的长期增强。然而，在低于惊厥剂量的青霉素（500国际单位/毫升）作用后，兴奋性突触后电位幅度也有类似增加，但并未产生持续性过度兴奋的其他特征。此外，爆发停止后，长期增强作用要么增加，要么保持稳定，而爆发后的振荡会随着时间逐渐减弱。低剂量的AMPA/海人藻酸拮抗剂6-氰基-7-硝基喹喔啉-2,3-二酮可将增强后的兴奋性突触后电位恢复到对照水平，减少但并未消除爆发后的振荡。强直刺激诱导的长期增强作用并未重现爆发后出现的过度兴奋状态。这些发现表明，阻断GABAA介导的抑制作用所引起的癫痫样爆发会诱导长期增强作用，这部分导致了持续性爆发诱导的过度兴奋，但不足以完全解释这种现象。对正常记忆至关重要的海马体，也常常是难治性癫痫发作的起源部位。海马体中类似癫痫发作的放电会诱导突触效能的长期增加，类似于被认为是正常记忆基础的那些变化。这种形式的长期增强作用促成了癫痫样活动后持续存在的过度兴奋状态的网络振荡特征，但不足以完全解释这些特征。癫痫发作可能会激活正常的记忆机制，这会增加神经元的兴奋性，并使海马网络更容易发生进一步的癫痫发作。这可能部分解释了海马癫痫病灶倾向于变得难治的原因。
