Wuarin J P, Dudek F E
Department of Anatomy, Colorado State University, Fort Collins 80523, USA.
J Neurosci. 1996 Jul 15;16(14):4438-48. doi: 10.1523/JNEUROSCI.16-14-04438.1996.
Mossy fiber sprouting has been proposed to lead to new excitatory connections between dentate granule cells, which in turn cause electrographic seizures. We tested this hypothesis in hippocampal slices from rats made epileptic-by kainate injections. The Timm's histological method revealed intense staining of the inner molecular layer in slices from all kainate-treated rats. In bicuculline (10 microM) and 6 mM [K +]o, antidromic stimulation of the granule cells evoked bursts of population spikes superimposed on long-lasting negative shifts in all slices tested from all kainate-treated rats. Long-duration (2-47 sec), seizure-like bursts with tonic and clonic components occurred spontaneously (53%) or in response to antidromic stimulation (81%). Under identical conditions, prolonged bursts were never seen in slices from controls or from kainate-injected rats 2-4 d after treatment. Glutamate microdrops applied in the granule cell layer evoked abrupt increases in the frequency of excitatory postsynaptic potentials (EPSPs) in two thirds of the cells tested. Glutamate microstimulation was effective at several sites in the granule cell layer but ineffective in the hilus. The proportion of granule cells responding to local application of glutamate by an increase in EPSPs was higher in slices with long bursts (80% with bursts of > 3 sec) than in slices with shorter bursts (33% with bursts of < 3 sec). Glutamate microstimulation did not affect EPSPs in granule cells from control preparations. These results support the hypothesis that kainate-induced mossy fiber sprouting forms new excitatory connections between granule cells and can lead to increased seizure susceptibility in the dentate gyrus.
有人提出苔藓纤维发芽会导致齿状颗粒细胞之间形成新的兴奋性连接，进而引发脑电图癫痫发作。我们在通过注射红藻氨酸诱发癫痫的大鼠海马切片中验证了这一假设。Timm组织学方法显示，所有经红藻氨酸处理的大鼠切片中，内分子层均有强烈染色。在荷包牡丹碱（10微摩尔）和6毫摩尔细胞外钾离子浓度条件下，对颗粒细胞进行逆向刺激，在所有经红藻氨酸处理的大鼠测试切片中，均可诱发群体峰电位爆发，并叠加有持久的负向偏移。长时程（2 - 47秒）、具有强直和阵挛成分的癫痫样爆发自发出现（53%）或由逆向刺激诱发（81%）。在相同条件下，对照组或处理后2 - 4天注射红藻氨酸的大鼠切片中从未出现过长时程爆发。在颗粒细胞层施加谷氨酸微滴，在三分之二的测试细胞中诱发兴奋性突触后电位（EPSP）频率突然增加。谷氨酸微刺激在颗粒细胞层的几个部位有效，但在海马门无效。在长时程爆发的切片中（爆发时长>3秒时为80%），对局部施加谷氨酸产生EPSP增加反应的颗粒细胞比例高于短时程爆发的切片（爆发时长<3秒时为33%）。谷氨酸微刺激对对照制剂的颗粒细胞中的EPSP没有影响。这些结果支持了以下假设：红藻氨酸诱导的苔藓纤维发芽在颗粒细胞之间形成了新的兴奋性连接，并可导致齿状回癫痫易感性增加。
