Synaptic hyperexcitability of deep layer neocortical cells in a genetic model of absence seizures
Synaptic hyperexcitability of deep layer neocortical cells in a genetic model of absence seizures
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DOI：
10.1111/j.1601-183x.2005.00148.x
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发表时间：
2006-02-01
影响因子：
2.5
通讯作者：
Avoli, M
中科院分区：
文献类型：
--
作者：
D'Antuono, M;Inaba, Y;Avoli, M
我们在体外脑切片制备中使用锐电极，细胞内记录来研究癫痫大鼠（180-210天龄）Wistar白化葛兰素/瑞氏（WAG/Rij）和年龄匹配的非癫痫对照（NEC）大鼠位于深层（距pia bbb900 μ m）的新皮质神经元的兴奋性。Wistar白化Glaxo/Rijswijk大鼠在体内表现出与广泛性峰波（SW）放电相关的失神癫痫的遗传模型。当充满神经生物素时，这些神经元具有典型的锥体形状，具有广泛的顶端和基部树突树；此外，WAG/Rij细胞和NEC细胞具有相似的基本电生理和重复放电特性。电刺激下脑白质或新皮层均可诱发兴奋性突触后电位（EPSPs）和超极化抑制性突触后电位（IPSPs）序列；然而，在55个定期放电的WAG/Rij细胞中的24个，而25个NEC神经元中只有2个，我们发现了一个晚期EPSP，(1)导致动作电位放电，(2)被n -甲基- d -天氨酸（NMDA）受体拮抗剂3,3-(2- carboxypperazine -4-yl)-丙基-1-膦酸盐（20 μ M; n = 8/8 WAG/Rij细胞）所消除。最后，我们发现在应用谷氨酸受体拮抗剂时记录的刺激诱导IPSP的快、慢组分在两种菌株中具有相似的逆转电位，而快速IPSP的峰值电导在WAG/Rij细胞中显著降低。这些发现证明，在位于新皮层深层的癫痫WAG/Rij大鼠神经元中，由NMDA受体介导的突触兴奋性增加。我们认为这种机制可能有助于在体内启动和维持广泛性脑电放电。
We used sharp-electrode, intracellular recordings in an in vitro brain slice preparation to study the excitability of neocortical neurons located in the deep layers (> 900 mu m from the pia) of epileptic (180-210-days old) Wistar Albino Glaxo/Rijswijk (WAG/Rij) and age-matched, non-epileptic control (NEC) rats. Wistar Albino Glaxo/Rijswijk rats represent a genetic model of absence seizures associated with generalized spike and wave (SW) discharges in vivo. When filled with neurobiotin, these neurons had a typical pyramidal shape with extensive apical and basal dendritic trees; moreover, WAG/Rij and NEC cells had similar fundamental electrophysiological and repetitive firing properties. Sequences of excitatory postsynaptic potentials (EPSPs) and hyperpolarizing inhibitory postsynaptic potentials (IPSPs) were induced in both the strains by electrical stimuli delivered to the underlying white matter or within the neocortex; however, in 24 of 55 regularly firing WAG/Rij cells but only in 2 of 25 NEC neurons, we identified a late EPSP that (1) led to action potential discharge and (2) was abolished by the N-methyl-D-aspartate (NMDA) receptor antagonist 3,3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonate (20 mu M; n = 8/8 WAG/Rij cells). Finally, we found that the fast and slow components of the stimulus-induced IPSPs recorded during the application of glutamatergic receptor antagonists had similar reversal potentials in the two strains, while the peak conductance of the fast IPSP was significantly reduced in WAG/Rij cells. These findings document an increase in synaptic excitability that is mediated by NMDA receptors, in epileptic WAG/Rij rat neurons located in neocortical deep layers. We propose that this mechanism may be instrumental for initiating and maintaining generalized SW discharges in vivo.