Dietrich D, Podlogar M, Ortmanns G, Clusmann H, Kral T
Experimental Neurophysiology, Department of Neurosurgery, NCH U1 R035, University Clinic Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany.
Brain Res. 2005 Jan 25;1032(1-2):123-30. doi: 10.1016/j.brainres.2004.10.060.
The dentate gyrus is believed to play an important pathophysiological role during experimentally induced kindling. In this study, we investigated whether an altered content of the calcium binding protein calbindin-D(28k) or an increased intrinsic excitability of hippocampal granule cells contribute to the induction of the kindling phenomenon. We determined the firing pattern of granule cells in hippocampal slices using perforated patch-clamp recordings in current clamp mode. The expression of calbindin-D(28k) and glutamic acid decarboxylase (GAD(67)) by granule cells was analyzed immunohistochemically. Rats developed secondarily generalized limbic seizures within approximately 11 days of twice-daily stimulation of the amygdala. As reported for other kindling paradigms, this protocol induced a clear up-regulation of GAD(67) in granule cells, indicating their involvement in the induced neuronal activity. However, when comparing kindled and control rats, we could not detect any differences in intrinsic excitability: Firing frequency, after-hyperpolarisations, action potentials, input resistance and membrane potentials were nearly identical between both groups. Furthermore, we did not observe any differences in the calbindin-D(28k) immunoreactivity between groups. In every slice, virtually all granule cells were found to be strongly calbindin-D(28k) positive, and there was no apparent reduction in the general level of calbindin-D(28k) expression. We conclude that changes in intrinsic membrane properties or in the calbindin-D(28k) content of granule cells are not necessary for the development of amygdala kindling.
齿状回被认为在实验性诱导点燃过程中发挥重要的病理生理作用。在本研究中，我们调查了钙结合蛋白钙结合蛋白-D（28k）含量的改变或海马颗粒细胞内在兴奋性的增加是否有助于点燃现象的诱导。我们使用电流钳模式下的穿孔膜片钳记录来确定海马切片中颗粒细胞的放电模式。通过免疫组织化学分析颗粒细胞中钙结合蛋白-D（28k）和谷氨酸脱羧酶（GAD（67））的表达。大鼠在每天两次刺激杏仁核约11天内出现继发性全身性边缘性癫痫发作。正如其他点燃范式所报道的那样，该方案诱导颗粒细胞中GAD（67）明显上调，表明它们参与了诱导的神经元活动。然而，在比较点燃大鼠和对照大鼠时，我们未检测到内在兴奋性的任何差异：两组之间的放电频率、超极化后电位、动作电位、输入电阻和膜电位几乎相同。此外，我们未观察到两组之间钙结合蛋白-D（28k）免疫反应性的任何差异。在每一片切片中，几乎所有颗粒细胞都被发现强烈表达钙结合蛋白-D（28k），并且钙结合蛋白-D（28k）表达的总体水平没有明显降低。我们得出结论，颗粒细胞内在膜特性或钙结合蛋白-D（28k）含量的变化对于杏仁核点燃的发展不是必需的。
