Ribak C E, Tran P H, Spigelman I, Okazaki M M, Nadler J V
Department of Anatomy and Neurobiology, University of California at Irvine, College of Medicine, Irvine, California 92697-1275, USA.
J Comp Neurol. 2000 Dec 11;428(2):240-53. doi: 10.1002/1096-9861(20001211)428:2<240::aid-cne4>3.0.co;2-q.
Mossy fiber sprouting into the inner molecular layer of the dentate gyrus is an important neuroplastic change found in animal models of temporal lobe epilepsy and in humans with this type of epilepsy. Recently, we reported in the perforant path stimulation model another neuroplastic change for dentate granule cells following seizures: hilar basal dendrites (HBDs). The present study determined whether status epilepticus-induced HBDs on dentate granule cells occur in the pilocarpine model of temporal lobe epilepsy and whether these dendrites are targeted by mossy fibers. Retrograde transport of biocytin following its ejection into stratum lucidum of CA3 was used to label granule cells for both light and electron microscopy. Granule cells with a heterogeneous morphology, including recurrent basal dendrites, and locations outside the granule cell layer were observed in control preparations. Preparations from both pilocarpine and kainate models of temporal lobe epilepsy also showed granule cells with HBDs. These dendrites branched and extended into the hilus of the dentate gyrus and were shown to be present on 5% of the granule cells in pilocarpine-treated rats with status epilepticus, whereas control rats had virtually none. Electron microscopy was used to determine whether HBDs were postsynaptic to axon terminals in the hilus, a site where mossy fiber collaterals are prevalent. Labeled granule cell axon terminals were found to form asymmetric synapses with labeled HBDs. Also, unlabeled, large mossy fiber boutons were presynaptic to HBDs of granule cells. These results indicate that HBDs are present in the pilocarpine model of temporal lobe epilepsy, confirm the presence of HBDs in the kainate model, and show that HBDs are postsynaptic to mossy fibers. These new mossy fiber synapses with HBDs may contribute to additional recurrent excitatory circuitry for granule cells.
苔藓纤维向齿状回内分子层的发芽是在颞叶癫痫动物模型和患有此类癫痫的人类中发现的一种重要的神经可塑性变化。最近,我们在穿通通路刺激模型中报道了癫痫发作后齿状颗粒细胞的另一种神经可塑性变化:门区基底树突(HBDs)。本研究确定了在颞叶癫痫的毛果芸香碱模型中,癫痫持续状态诱导的齿状颗粒细胞上的HBDs是否出现,以及这些树突是否被苔藓纤维靶向。将生物素注入CA3的透明层后进行逆行运输,用于标记颗粒细胞,以进行光学显微镜和电子显微镜观察。在对照制剂中观察到形态各异的颗粒细胞,包括回返性基底树突,以及位于颗粒细胞层之外的位置。来自颞叶癫痫的毛果芸香碱和海藻酸模型的制剂也显示出具有HBDs的颗粒细胞。这些树突分支并延伸到齿状回的门区,在癫痫持续状态的毛果芸香碱处理大鼠中,5%的颗粒细胞上有这些树突,而对照大鼠几乎没有。电子显微镜用于确定HBDs是否是门区轴突终末的突触后部位,门区是苔藓纤维侧支普遍存在的部位。发现标记的颗粒细胞轴突终末与标记的HBDs形成不对称突触。此外,未标记的大型苔藓纤维终扣是颗粒细胞HBDs的突触前成分。这些结果表明,HBDs存在于颞叶癫痫的毛果芸香碱模型中,证实了海藻酸模型中存在HBDs,并表明HBDs是苔藓纤维的突触后成分。这些与HBDs形成的新的苔藓纤维突触可能有助于颗粒细胞额外的反复兴奋性回路。