Jensen M S, Yaari Y
PharmaBiotech, Institute of Physiology, Aarhus University, Denmark.
J Neurophysiol. 1997 Mar;77(3):1224-33. doi: 10.1152/jn.1997.77.3.1224.
Perfusing rat hippocampal slices with high-K+ (7.5 mM) saline induced brief population bursts originating in CA3 at 0.5-1 Hz and spreading synaptically into CA1. In 42% of the slices the brief bursts evoked in CA1 gave way every 0.5-2 s to sustained ictal (or seizure) episode with tonic and clonic components. Paired intra- and extracellular recordings in the CA1 pyramidal layer were used to characterize the synaptic and nonsynaptic mechanisms generating the brief and sustained epileptiform events. The interictal, tonic, or clonic primary burst response in CA1 comprised a spindle-shaped, tight cluster (170-180 Hz) of five to seven population spikes. Bursts evoked between sequential seizures (interictal bursts) were initially small and progressively increased in size. Concurrently, basal extracellular K+ concentration ([K+]o] increased from 6.5 to 7.5 mM. The tonic event emanated from a large primary burst and comprised prolonged (> 1 s), self-sustained afterdischarge, associated with a rise in [K+]o to 12 mM. Bursts generated during the subsequent [K+]o decline (clonic bursts) also were large and followed by some afterdischarge. They became small during [K+]o undershoot to 6.5 mM. Intrinsically burst firing pyramidal cells (PCs) were recruited before or at the very onset of the primary population burst and fired repetitively during its course. Nonbursters were recruited > or = 10 ms after the beginning of the primary burst and fired, on average, only one spike. The PCs depolarized during the primary burst and subsequent afterdischarge. The primary depolarizing shift was larger in bursters than in nonbursters. Both bursters and nonbursters fired repetitively, albeit intermittently, during tonic and clonic afterdischarge. Throughout the interictal-ictal cycle intracellular spikes were time-locked to population spikes, indicating that PCs fire in tight synchrony. Differential recording of transmembrane potentials unmasked rapid (4-7 ms) transmembrane depolarizing potentials of up to 10 mV, coincident with population spikes. We conclude that in the high-K+ model of hippocampal epilepsy, the local generation of population bursts in CA1 is led by intrinsic bursters, which recruit and synchronize other PCs by synaptic, electrical, and K(+)-mediated excitatory interactions. The cycling between interictal, tonic, and clonic events appears to result from feedback interactions between neuronal discharge and [K+]o.
用高钾（7.5 mM）生理盐水灌注大鼠海马切片，可诱发始于CA3区、频率为0.5 - 1 Hz的短暂群体爆发，并通过突触扩散至CA1区。在42%的切片中，CA1区诱发的短暂爆发每隔0.5 - 2秒就会转变为伴有强直和阵挛成分的持续性发作（或癫痫）事件。利用CA1锥体细胞层的细胞内和细胞外配对记录来表征产生短暂和持续性癫痫样事件的突触和非突触机制。CA1区的发作间期、强直或阵挛性初级爆发反应包括一个纺锤形、紧密聚集（170 - 180 Hz）的五到七个群体峰电位。连续癫痫发作之间诱发的爆发（发作间期爆发）最初较小，随后规模逐渐增大。同时，细胞外基础钾离子浓度（[K⁺]ₒ）从6.5 mM升高至7.5 mM。强直事件源于一个大的初级爆发，包括持续时间延长（> 1秒）、自我维持的后放电，同时[K⁺]ₒ升高至12 mM。随后[K⁺]ₒ下降期间产生的爆发（阵挛性爆发）也较大，随后有一些后放电。在[K⁺]ₒ低于6.5 mM的超射期间，它们会变小。内在爆发性放电的锥体细胞（PCs）在初级群体爆发之前或刚开始时被募集，并在爆发过程中重复放电。非爆发性细胞在初级爆发开始后≥10毫秒被募集，平均仅发放一个峰电位。PCs在初级爆发和随后的后放电期间发生去极化。初级去极化转变在爆发性细胞中比在非爆发性细胞中更大。在强直和阵挛性后放电期间，爆发性细胞和非爆发性细胞都会间歇性地重复放电。在整个发作间期 - 发作周期中，细胞内峰电位与群体峰电位在时间上锁定，表明PCs紧密同步放电。跨膜电位的差异记录揭示了与群体峰电位同时出现的高达10 mV的快速（4 - 7毫秒）跨膜去极化电位。我们得出结论，在海马癫痫的高钾模型中，CA1区群体爆发的局部产生由内在爆发性细胞主导，这些细胞通过突触、电和钾离子介导的兴奋性相互作用募集并同步其他PCs。发作间期、强直和阵挛性事件之间的循环似乎是由神经元放电与[K⁺]ₒ之间的反馈相互作用导致的。
