Shao Li-Rong, Dudek F Edward
Dept. of Biomedical Sciences, Anatomy and Neurobiology Section, 1617 Campus Delivery, Colorado State University, Fort Collins, CO 80523, USA.
J Neurophysiol. 2004 Sep;92(3):1366-73. doi: 10.1152/jn.00131.2004. Epub 2004 Apr 14.
Formation of local excitatory circuits may contribute to epileptogenesis. We tested the hypothesis that epileptogenesis is associated with increased recurrent excitation in the hippocampal CA1 area of rats with kainate-induced epilepsy. Whole cell recordings were obtained during focal flash photolysis of caged glutamate, which served as a focal excitant to activate local pyramidal cells and to study possible connections between neurons. Kainate-treated rats with spontaneous seizures were studied months after status epilepticus and were compared with saline-injected control rats. Experiments were done in isolated CA1 minislices and in bicuculline to block GABA(A) receptors. Spontaneous excitatory postsynaptic currents (sEPSCs) were present in 42% of the CA1 pyramidal cells from controls and 62% from kainate-treated rats. The frequency of sEPSCs in the kainate group was significantly higher than that in the control group, but mean amplitude was not different. Flash photolysis of caged glutamate on the somatodendritic area of CA1 pyramidal neurons caused a burst of action potentials. Local excitatory connections between CA1 pyramidal cells were found in 4 of 48 neurons (8%) in slices from control animals, but in significantly more neurons (12 of 37; 32%) from rats with kainate-induced epilepsy exhibited interconnections (P < 0.001). Photoactivation of glutamate on recorded CA1 pyramidal cells in the kainate group sometimes caused afterdischarges, but not in controls. The kainate-treated rats with pyramidal cells that responded to photostimulaltion with repetitive EPSCs appeared to have experienced more severe seizures. These data provide new electrophysiological evidence for the formation of recurrent excitatory circuits in the CA1 area of rats with kainate-induced epilepsy.
局部兴奋性回路的形成可能促成癫痫发生。我们检验了这样一个假说：癫痫发生与海藻酸诱导癫痫大鼠海马CA1区反复性兴奋增强有关。在笼形谷氨酸的局灶闪光光解过程中进行全细胞记录，笼形谷氨酸作为局灶性刺激物来激活局部锥体细胞并研究神经元之间可能的联系。对癫痫持续状态数月后出现自发性癫痫发作的海藻酸处理大鼠进行研究，并与注射生理盐水的对照大鼠进行比较。实验在分离的CA1微小切片中进行，并使用荷包牡丹碱阻断GABAA受体。对照组42%的CA1锥体细胞和海藻酸处理组62%的CA1锥体细胞存在自发性兴奋性突触后电流（sEPSCs）。海藻酸组sEPSCs的频率显著高于对照组，但平均幅度无差异。对CA1锥体细胞的树突-胞体区域进行笼形谷氨酸的闪光光解会引发一阵动作电位。在对照动物切片的48个神经元中有4个（8%）发现了CA1锥体细胞之间的局部兴奋性联系，但在海藻酸诱导癫痫的大鼠切片中，有更多神经元（37个中的12个；32%）表现出相互联系（P<0.001）。海藻酸组中记录到的CA1锥体细胞上谷氨酸的光激活有时会引起后放电，但对照组则不会。对光刺激产生重复性兴奋性突触后电流反应的锥体细胞的海藻酸处理大鼠似乎经历了更严重的癫痫发作。这些数据为海藻酸诱导癫痫的大鼠CA1区反复性兴奋性回路的形成提供了新的电生理证据。
