Davenport C J, Brown W J, Babb T L
Division of Neuropathology, University of California, Los Angeles 90024.
Exp Neurol. 1990 Aug;109(2):180-90. doi: 10.1016/0014-4886(90)90072-z.
The present study examined the bilateral synaptic rearrangements of presumed gamma-aminobutyric acid (GABAergic) inhibitory axons and mossy fiber (presumed excitatory) recurrent collaterals following intrahippocampal kainic acid (KA) injection. Glutamate decarboxylase immunoreactivity (GAD-IR) was used to study inhibitory axon terminal sprouting, following 0.5 microgram KA/0.2 microliter injected unilaterally into the posterior hippocampus of rats (n = 16), with survival periods of 14, 28, and 120 days. The age-matched control animals (n = 9) received intrahippocampal 0.2 microliter saline (sham, n = 4) or no injection (normal, n = 5). To study mossy fiber synaptic rearrangements, 0.5 microgram KA/0.2 microliter volumes were injected unilaterally into the posterior hippocampus of rats (n = 10), with survival periods from 14, 28, and 120 days, and Timm sulfide-stained tissue sections were compared to age-matched sham (n = 4) or normal controls (n = 4). At 14 through 120 days after posterior KA injection, GAD-IR puncta were significantly increased in the ipsi- and contralateral inner molecular layers (IML) of the fascia dentata (FD) when compared to sham or normal controls. KA lesion also induced mossy fiber recurrent collateral sprouting into the ipsi- and contralateral FD IMLs. The loss of both the commissural and ipsilateral associational afferents to the FD apparently induced sprouting into their ipsi- and contralateral termination zones by granule cell mossy fibers and GAD-IR axons, thus establishing an abnormal circuitry near the observed pathology in the kainate model of epilepsy. Although reactive synaptogenesis of mossy fibers producing monosynaptic excitation may be one mechanism for KA epileptogenicity, the concurrent sprouting of GABAergic terminals in the same IML zone of the FD suggests that anomalous inhibitory synapses may contribute to chronic KA hippocampal hyperexcitability.
本研究检测了海马内注射 kainic 酸（KA）后，假定的γ-氨基丁酸（GABA 能）抑制性轴突和苔藓纤维（假定为兴奋性）回返侧支的双侧突触重排情况。采用谷氨酸脱羧酶免疫反应性（GAD-IR）研究抑制性轴突终末发芽，将 0.5 微克 KA/0.2 微升单侧注射到大鼠（n = 16）后海马中，存活期分别为 14、28 和 120 天。年龄匹配的对照动物（n = 9）接受海马内注射 0.2 微升生理盐水（假手术组，n = 4）或不注射（正常组，n = 5）。为研究苔藓纤维突触重排，将 0.5 微克 KA/0.2 微升体积单侧注射到大鼠（n = 10）后海马中，存活期为 14、28 和 120 天，并将 Timm 硫化物染色的组织切片与年龄匹配的假手术组（n = 4）或正常对照组（n = 4）进行比较。在后海马注射 KA 后 14 至 120 天，与假手术组或正常对照组相比，齿状回（FD）同侧和对侧内分子层（IML）中的 GAD-IR 斑点显著增加。KA 损伤还诱导苔藓纤维回返侧支向同侧和对侧 FD IML 发芽。向 FD 的连合和同侧联合传入纤维的丧失显然诱导颗粒细胞苔藓纤维和 GAD-IR 轴突向其同侧和对侧终末区发芽，从而在癫痫的海藻酸盐模型中观察到的病变附近建立异常回路。虽然产生单突触兴奋的苔藓纤维的反应性突触形成可能是 KA 致痫性的一种机制，但 FD 同一 IML区中 GABA 能终末的同时发芽表明异常抑制性突触可能导致慢性 KA 海马过度兴奋。
