GABAC RECEPTORS ARE FUNCTIONALLY EXPRESSED IN THE INTERMEDIATE ZONE AND REGULATE RADIAL MIGRATION IN THE EMBRYONIC MOUSE NEOCORTEX
GABAC RECEPTORS ARE FUNCTIONALLY EXPRESSED IN THE INTERMEDIATE ZONE AND REGULATE RADIAL MIGRATION IN THE EMBRYONIC MOUSE NEOCORTEX
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DOI：
10.1016/j.neuroscience.2010.01.049
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发表时间：
2010-04-28
期刊：
影响因子：
3.3
通讯作者：
Luhmann, H. J.
中科院分区：
文献类型：
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作者：
Denter, D. G.;Heck, N.;Luhmann, H. J.
大脑皮层的径向神经元迁移依赖于营养因子和不同电压和配体门控通道的激活。为了研究GABA(C)受体在径向迁移中的功能作用，我们利用器官型新皮层切片培养，分析了特异性GABA(A)和GABA(C)受体拮抗剂对brdu标记神经元体外迁移的影响。这些实验表明，GABA(A)特异性抑制剂双库碱甲碘化物促进了神经元的迁移，而GABA(C)特异性抑制剂（1,2,5,6-四氢吡啶-4-基）甲基膦酸（TPMPA）阻碍了神经元的迁移。TPMPA与双丘碱甲氧蝶呤或非特异性嗜离子性GABA受体拮抗剂微毒素共同应用均阻碍了迁移，表明GABA(C)受体介导的作用占主导地位。添加特异性GABA(C)受体激动剂顺式-4-氨基酸（CACA）也阻碍了迁移，这表明生理上的GABA能刺激需要适当的功能。使用GABA(C)受体mRNA特异性探针进行的RT-PCR实验和使用针对rho亚基的抗体进行的Western blot检测显示，GABA(C)受体mRNA和翻译的GABA(C)受体蛋白在未成熟皮层中表达。钙绿微荧光Ca2+成像显示GABA(A)和GABA(C)受体在中间区功能表达，而只在上皮层板观察到GABA(A)受体介导的反应。综上所述，这些结果表明GABA(C)受体的激活是准确迁移的先决条件，GABA(C)受体在中间区有功能表达。(c) 2010 ibro。Elsevier Ltd.出版。版权所有。
Radial neuronal migration in the cerebral cortex depends on trophic factors and the activation of different voltage- and ligand-gated channels. To examine the functional role of GABA(C) receptors in radial migration we analyzed the effects of specific GABA(A) and GABA(C) receptor antagonists on the migration of BrdU-labeled neurons in vitro using organotypic neocortical slice cultures. These experiments revealed that the GABA(A) specific inhibitor bicuculline methiodide facilitated neuronal migration, while the GABA(C) specific inhibitor (1,2,5,6-tetrahydropyridine-4-yl) methylphosphinic-acid (TPMPA) impeded migration. Co-application of TPMPA and bicuculline methiodide or the unspecific ionotropic GABA receptor antagonist picrotoxin both impeded migration, suggesting that the GABA(C) receptor mediated effects dominate. Addition of the specific GABA(C) receptor agonist cis-4-aminocrotonic acid (CACA) also hampered migration, indicating that a physiological GABAergic stimulation is required for appropriate function. RT-PCR experiments using specific probes for GABA(C) receptor mRNA and Western blot assays using an antibody directed against rho subunits revealed the expression of GABA(C) receptor mRNA and translated GABA(C) receptor protein in the immature cortex. Microfluorimetric Ca2+ imaging in neurons of identified cortical layers using Calcium Green revealed the functional expression of GABA(A) and GABA(C) receptors in the intermediate zone, while only GABA(A) receptor mediated responses were observed in the upper cortical plate. In summary, these results demonstrate that activation of GABA(C) receptors is a prerequisite for accurate migration and that GABA(C) receptors are functionally expressed in the intermediate zone. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.