Codadu Neela K, Graham Robert T, Burman Richard J, Jackson-Taylor R Thomas, Raimondo Joseph V, Trevelyan Andrew J, Parrish R Ryley
Institute of Neuroscience, Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom.
Division of Cell Biology, Department of Human Biology, Neuroscience Institute and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Physiol Rep. 2019 Oct;7(19):e14226. doi: 10.14814/phy2.14226.
Much debate exists about how the brain transitions into an epileptic seizure. One source of confusion is that there are likely to be critical differences between experimental seizure models. To address this, we have compared the evolving activity patterns in two widely used in vitro models of epileptic discharges. Brain slices from young adult mice were prepared in the same way and bathed either in 0 Mg or 100 µmol/L 4AP artificial cerebrospinal fluid. We have found that while local field potential recordings of epileptiform discharges in the two models appear broadly similar, patch-clamp analysis reveals an important difference in the relative degree of glutamatergic involvement. 4AP affects parvalbumin-expressing interneurons more than other cortical populations, destabilizing their resting state and inducing spontaneous bursting behavior. Consequently, the most prominent pattern of transient discharge ("interictal event") in this model is almost purely GABAergic, although the transition to seizure-like events (SLEs) involves pyramidal recruitment. In contrast, interictal discharges in 0 Mg are only maintained by a very large glutamatergic component that also involves transient discharges of the interneurons. Seizure-like events in 0 Mg have significantly higher power in the high gamma frequency band (60-120Hz) than these events do in 4AP, and are greatly delayed in onset by diazepam, unlike 4AP events. We, therefore, conclude that the 0 Mg and 4AP models display fundamentally different levels of glutamatergic drive, demonstrating how ostensibly similar pathological discharges can arise from different sources. We contend that similar interpretative issues will also be relevant to clinical practice.
关于大脑如何转变为癫痫发作存在诸多争议。一个造成混淆的原因是实验性癫痫发作模型之间可能存在关键差异。为了解决这个问题，我们比较了两种广泛使用的癫痫放电体外模型中不断演变的活动模式。以相同方式制备来自年轻成年小鼠的脑片，并将其置于0 Mg或100 µmol/L 4-氨基吡啶（4AP）人工脑脊液中浸泡。我们发现，虽然两种模型中癫痫样放电的局部场电位记录大致相似，但膜片钳分析揭示了谷氨酸能参与程度的重要差异。4AP对表达小白蛋白的中间神经元的影响大于其他皮质细胞群，破坏其静息状态并诱导自发爆发行为。因此，该模型中最突出的瞬态放电模式（“发作间期事件”）几乎完全是γ-氨基丁酸能的，尽管向癫痫样事件（SLEs）的转变涉及锥体神经元的募集。相比之下，0 Mg中的发作间期放电仅由非常大的谷氨酸能成分维持，该成分也涉及中间神经元的瞬态放电。0 Mg中的癫痫样事件在高γ频段（60 - 120Hz）的功率明显高于4AP中的这些事件，并且与4AP事件不同，地西泮会大大延迟其发作。因此，我们得出结论，0 Mg和4AP模型显示出谷氨酸能驱动的根本不同水平，表明表面上相似的病理性放电可源于不同来源。我们认为类似的解释问题在临床实践中也会相关。
