Wittner L, Eross L, Czirják S, Halász P, Freund T F, Maglóczky Zs
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
Brain. 2005 Jan;128(Pt 1):138-52. doi: 10.1093/brain/awh339. Epub 2004 Nov 17.
Temporal lobe epilepsy (TLE) is known to be linked to an impaired balance of excitation and inhibition. Whether inhibition is decreased or preserved in the human epileptic hippocampus, beside the excess excitation, is still a debated question. In the present study, quantitative light and electron microscopy has been performed to analyse the distribution, morphology and input-output connections of parvalbumin (PV)-immunopositive interneurons, together with the entire perisomatic input of pyramidal cells, in the human control and epileptic CA1 region. Based on the degree of cell loss, the patients with therapy-resistant TLE formed four pathological groups. In the non-sclerotic CA1 region of TLE patients, where large numbers of pyramidal cells are preserved, the number of PV-immunopositive cell bodies decreased, whereas axon terminal staining, and the distribution of their postsynaptic targets was not altered. The synaptic coverage of CA1 pyramidal cell axon initial segments (AISs) remained unchanged in the epileptic tissue. The somatic inhibitory input is also preserved; it has been decreased only in the cases with patchy pyramidal cell loss in the CA1 region (control, 0.637; epileptic with mild cell loss, 0.642; epileptic with patchy cell loss, 0.424 microm synaptic length/100 microm soma perimeter). The strongly sclerotic epileptic CA1 region, where pyramidal cells can hardly be seen, contains a very small number of PV-immunopositive elements. Our results suggest that perisomatic inhibitory input is preserved in the epileptic CA1 region as long as pyramidal cells are present. Basket and axo-axonic cells survive in epilepsy if their original targets are present, although many of them lose their PV content or PV immunoreactivity. An efficient perisomatic inhibition is likely to take part in the generation of abnormal synchrony in the non-sclerotic epileptic CA1 region, and thus participate in the maintenance of epileptic seizures driven, for example, by hyperactive afferent input.
颞叶癫痫（TLE）已知与兴奋和抑制的平衡受损有关。除了过度兴奋外，人类癫痫海马体中的抑制是减少还是保留，仍是一个有争议的问题。在本研究中，已进行定量光镜和电镜分析，以研究人类对照和癫痫CA1区中小清蛋白（PV）免疫阳性中间神经元的分布、形态和输入-输出连接，以及锥体细胞的整个胞体周围输入。根据细胞丢失程度，将耐药性TLE患者分为四个病理组。在TLE患者的非硬化性CA1区，大量锥体细胞得以保留，PV免疫阳性细胞体数量减少，而轴突终末染色及其突触后靶点的分布未改变。癫痫组织中CA1锥体细胞轴突起始段（AIS）的突触覆盖保持不变。胞体抑制性输入也得以保留；仅在CA1区有散在锥体细胞丢失的病例中有所减少（对照组，0.637；轻度细胞丢失的癫痫组，0.642；散在细胞丢失的癫痫组，0.424微米突触长度/100微米胞体周长）。在严重硬化的癫痫CA1区，几乎看不到锥体细胞，含有极少数PV免疫阳性成分。我们的结果表明，只要锥体细胞存在，胞体周围抑制性输入在癫痫CA1区就能保留。如果篮状细胞和轴-轴突细胞的原始靶点存在，它们在癫痫中就能存活，尽管其中许多细胞会失去PV含量或PV免疫反应性。有效的胞体周围抑制可能参与非硬化性癫痫CA1区异常同步性的产生，从而参与例如由活跃传入输入驱动的癫痫发作的维持。
