Wittner L, Eross L, Szabó Z, Tóth Sz, Czirják S, Halász P, Freund T F, Maglóczky Z S
Institute of Experimental Medicine, Hungarian Academy of Sciences, PO Box 67, H-1450, Budapest, Hungary.
Neuroscience. 2002;115(3):961-78. doi: 10.1016/s0306-4522(02)00264-6.
The distribution, morphology, synaptic coverage and postsynaptic targets of calbindin-containing interneurons and afferent pathways have been analyzed in the control and epileptic CA1 region of the human hippocampus. Numerous calbindin-positive interneurons are preserved even in the strongly sclerotic CA1 region. The morphology of individual cells is altered: the cell body and dendrites become spiny, the radially oriented dendrites disappear, and are replaced by a large number of curved, distorted dendrites. Even in the non-sclerotic epileptic samples, where pyramidal cells are present and calbindin-immunoreactive interneurons seem to be unchanged, some modifications could be observed at the electron microscopic level: they received more inhibitory synaptic input, and the calbindin-positive excitatory afferents - presumably derived from the CA1, the CA2 and/or the dentate gyrus - are sprouted. In the strongly sclerotic tissue, with the death of pyramidal cells, calbindin-positive terminals (belonging to interneurons and the remaining excitatory afferents) change their targets. Our data suggest that an intense synaptic reorganization takes place in the epileptic CA1 region, even in the non-sclerotic tissue, before the death of considerable numbers of pyramidal cells. Calbindin-positive interneurons participate in this reorganization: they show plastic changes in response to epilepsy. The enhanced inhibition of inhibitory interneurons may result in the disinhibition of pyramidal cells or in an abnormal synchrony in the output region of the hippocampus.
在人类海马体的对照和癫痫性CA1区域，已经对含钙结合蛋白的中间神经元和传入通路的分布、形态、突触覆盖和突触后靶点进行了分析。即使在严重硬化的CA1区域，仍保留着大量钙结合蛋白阳性中间神经元。单个细胞的形态发生了改变：细胞体和树突变得有棘，径向排列的树突消失，取而代之的是大量弯曲、扭曲的树突。即使在非硬化的癫痫样本中，锥体细胞存在且钙结合蛋白免疫反应性中间神经元似乎未发生变化，但在电子显微镜水平仍可观察到一些改变：它们接受了更多的抑制性突触输入，并且钙结合蛋白阳性的兴奋性传入纤维（可能源自CA1、CA2和/或齿状回）出现了发芽。在严重硬化的组织中，随着锥体细胞的死亡，钙结合蛋白阳性终末（属于中间神经元和剩余的兴奋性传入纤维）改变了它们的靶点。我们的数据表明，即使在大量锥体细胞死亡之前，癫痫性CA1区域，甚至在非硬化组织中，也会发生强烈的突触重组。钙结合蛋白阳性中间神经元参与了这种重组：它们表现出对癫痫的可塑性变化。抑制性中间神经元的抑制增强可能导致锥体细胞去抑制或海马体输出区域出现异常同步。
