Barbarosie M, Avoli M
Research Group on Cell Biology of Excitable Tissues, Montreal Neurological Institute, Department of Neurology, McGill University, Montreal, Qu-ebec, Canada H3A 2B4.
J Neurosci. 1997 Dec 1;17(23):9308-14. doi: 10.1523/JNEUROSCI.17-23-09308.1997.
Continuous application of 4-aminopyridine (4-AP, 50 microM) to combined slices of hippocampus-entorhinal cortex obtained from adult mice induces (1) interictal discharges that initiate in the CA3 area and propagate via the hippocampal regions CA1 and subiculum to the entorhinal cortex and return to the hippocampus through the dentate gyrus; and (2) ictal discharges that originate in the entorhinal cortex and propagate via the dentate gyrus to the hippocampus proper. Ictal discharges disappear over time, whereas synchronous interictal discharges continue to occur throughout the experiment. Lesioning the Schaffer collaterals abolishes interictal discharges in CA1, entorhinal cortex, and dentate gyrus and discloses entorhinal ictal discharges that propagate, via the dentate gyrus, to the CA3 subfield. Interictal discharges originating in CA3 also prevent the occurrence of ictal events generated in the entorhinal cortex during application of Mg2+-free medium. In both models, ictal discharge generation recorded in the entorhinal cortex after Schaffer collateral cut is prevented by mimicking CA3 neuronal activity through rhythmic electrical stimulation (0.25-1.5 Hz) of the CA1 hippocampal output region. Our findings demonstrate that interictal discharges of hippocampal origin control the expression of ictal epileptiform activity in the entorhinal cortex. Sectioning the Schaffer collaterals may model the chronic epileptic condition in which cell damage in the CA3 subfield results in loss of CA3 control over the entorhinal cortex. Hence, we propose that the functional integrity of hippocampal output neurons may represent a critical control point in temporal lobe epileptogenesis.
将4-氨基吡啶（4-AP，50微摩尔）持续应用于成年小鼠的海马-内嗅皮质联合切片，可诱导出：（1）发作间期放电，起始于CA3区，经海马CA1区和下托传播至内嗅皮质，再通过齿状回返回海马；（2）发作期放电，起源于内嗅皮质，经齿状回传播至海马本部。发作期放电随时间消失，而同步发作间期放电在整个实验过程中持续出现。切断Schaffer侧支可消除CA1、内嗅皮质和齿状回的发作间期放电，并揭示经齿状回传播至CA3亚区的内嗅发作期放电。CA3区起源的发作间期放电也可在应用无镁培养基时阻止内嗅皮质产生的发作期事件的发生。在这两种模型中，通过对海马CA1输出区进行节律性电刺激（0.25 - 1.5赫兹）模拟CA3神经元活动，可防止切断Schaffer侧支后在内嗅皮质记录到的发作期放电的产生。我们的研究结果表明，海马起源的发作间期放电控制着内嗅皮质发作期癫痫样活动的表达。切断Schaffer侧支可能模拟了慢性癫痫状态，其中CA3亚区的细胞损伤导致CA3对内嗅皮质的控制丧失。因此，我们提出海马输出神经元的功能完整性可能是颞叶癫痫发生的关键控制点。
