Otx1 promotes basal dendritic growth and regulates intrinsic electrophysiological and synaptic properties of layer V pyramidal neurons in mouse motor cortex-猫眼课题宝

DOI：

10.1016/j.neuroscience.2014.11.019

发表时间：

2015-01

期刊：

Neuroscience

影响因子：

3.3

通讯作者：

中科院分区：

医学3区

文献类型：

--

作者：

Y.-F. Zhang;L-X. Liu;Huateng Cao;L. Ou;J. Qu;Y. Wang;J.-G. Chen

转录因子otx1在大脑皮层的V层锥体细胞（L5PCs）中特异性表达。Otx1null突变小鼠在L5PCs的发育轴突修剪上存在缺陷，并表现为癫痫发作。然而，otx1在皮层神经元的电生理、形态学和突触学中的作用尚未得到充分的研究。本研究通过功能丧失和功能获得的方法研究了otx11对L5PCs神经元特性的影响。携带otx1 -null突变的小鼠L5PCs的基底树突结构测量值降低。相比之下，在t2 /3中，otx1过表达的锥体细胞（PCs）的基底树突大小增加，而该基因通常不表达。pc表现出动作电位的爆发和非爆发放电模式。otx1突变体的突发放电神经元比例减少，而过表达gotx1的神经元比例增加。在otx1突变小鼠中，虽然爆发放电数量减少，但低阈值爆发神经元的比例增加。此外，在otx1突变小鼠中，L5PCs之间形成的兴奋性促进突触连接占主导地位，与对照组中主要的抑制性突触连接形成鲜明对比。综上所述，这表明otx1突变小鼠皮层的神经网络活动增强。这些数据表明，otx1的表达对于L5PCs的树突形态、内在电生理和突触动力学的正常发育至关重要。该研究为L5PCs神经元和突触特性时空调控的分子机制提供了新的见解，并提高了我们对癫痫发作发生的理解。

The transcription factorOtx1is specifically expressed in layer V pyramidal cells (L5PCs) in the cerebral cortex.Otx1null mutant mice have a defect in the developmental axon pruning of L5PCs and show epileptic seizures. However, the role ofOtx1in electrophysiology, morphology and synaptology of the cortical neurons has not been fully investigated. This study examines the influences ofOtx1on neuronal properties of L5PCs by loss- and gain-of-function approaches. Mice with anOtx1-null mutation had decreased structural measurements of basal dendrites in L5PCs. In contrast, the size of basal dendrites was increased in theOtx1-over-expressed pyramidal cells (PCs) in L2/3 where the gene normally does not express. PCs showed burst and non-burst firing patterns of action potentials. The proportion of burst firing neurons was reduced in theOtx1mutant but increased in the neurons over-expressingOtx1. Although the burst firing population decreased, the proportion of those bursting neurons with a low threshold increased in theOtx1mutant mice. Moreover, excitatory facilitating synaptic connections formed between L5PCs were predominant in theOtx1mutant mice, which greatly contrasted with the predominant depressing synaptic connections in the controls. Taken together, it suggests an enhanced activity of neuronal network in the cortex ofOtx1mutant mice. These data indicate that theOtx1expression is essential for the normal development of dendritic morphology, intrinsic electrophysiology and synaptic dynamics of L5PCs. This study provides new insights into molecular mechanisms underlying the spatial and temporal regulation of neuronal and synaptic properties of L5PCs, and improves our understanding on the generation of epileptic seizures.