Otx1在小鼠癫痫样行为中的潜在作用机制:大脑皮质第5皮层锥体神经元生理功能的“调节者”  

The Potential Role of Otx1 in Epileptic-like Behavior Mice: the “Modulator” of Physiological Function of Layer V Pyramidal Neurons in the Cerebral Cortex

作　　者：张云峰[1,2] 文正伟[3] 

机构地区：[1]温州医科大学眼视光学院 [2]温州医科大学附属眼视光医院,温州325027 [3]温州医科大学基础医学院,温州325027

出　　处：《中国细胞生物学学报》2015年第5期663-670,共8页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(批准号:81301117);温州市科技计划项目(批准号:Y20140049)资助的课题~~

摘　　要：转录因子Otx1在大脑皮质第5皮层锥体神经元中特异性表达。该研究利用全细胞膜片钳记录技术和神经元三维形态模拟重构及定量分析平台探讨Otx1在小鼠癫痫样行为中的潜在作用机制。结果表明,在大脑皮质运动区第5皮层锥体神经元中鉴定到四种不同放电类型的神经元,即固有爆发式、节律性振荡爆发式、适应性规律式及紧张性放电型。与对照相比,Otx1突变小鼠中规律式放电神经元的比例显著升高,而爆发式放电神经元的比例显著减少并表现出增强的兴奋性。此外,Otx1突变促使神经元动作电位(action potential,AP)阈值、输入阻抗及快速后超极化电位都显著降低,进而使其兴奋性增强。Otx1突变降低神经元基树突形态结构复杂性,主要表现为基树突表面积、体积、分节表面积及分节体积的显著降低。可见,Otx1突变导致大脑皮质运动区第5皮层锥体神经元生理功能的改变可能是小鼠癫痫样行为的潜在原因。The transcription factor Otxl is specifically expressed in layer V pyramidal neurons （L5PNs） in the cerebral cortex. This study used the whole-cell patch clamp recording and 3D neuronal morphological recon- struction and analysis to investigate the potential role of Otxl in epileptic-like behavior mice. Four types of L5PNs with distinct firing patterns, namely intrinsically bursting （IB）, rhythmic oscillatory bursting （ROB）, adapting regular spiking （RSAD） and tonic firing （TF） were confirmed. Compared with controls, the proportion of regular spiking neurons increased significantly while the burst firing neurons decreased remarkably with enhanced excitability in the Otxl mutant mice. The AP-thresholds, input resistance and fast after-hyperpolarization of L5PNs decreased markedly in the Otxl mutant mice, leading to an enhanced neuronal excitability. Moreover, Otxl mutation reduced basal dendritic morphological structural complexity, which mainly exhibited as the significant decrements in the surface area, the volume, the segment surface area and the segment volume. It suggested that change in physiologi-cal function of L5PNs resulting from the mutation of Otxl in the cerebral cortex was a potential mechanism of the epileptic-like behavior of the Otxl mutant mice.

关 键 词：全细胞膜片钳记录 癫痫样行为 第5皮层锥体神经元 Otx1突变 基树突 

分 类 号：R742.1[医药卫生—神经病学与精神病学]