Crandall James E, McCarthy Deirdre M, Araki Kiyomi Y, Sims John R, Ren Jia-Qian, Bhide Pradeep G
Eunice Kennedy Shriver Center for Mental Retardation, Physiology, University of Massachusetts Medical School, Waltham, Massachusetts 02452, USA.
J Neurosci. 2007 Apr 4;27(14):3813-22. doi: 10.1523/JNEUROSCI.5124-06.2007.
GABA neurons of the cerebral cortex and other telencephalic structures are produced in the basal forebrain and migrate to their final destinations during the embryonic period. The embryonic basal forebrain is enriched in dopamine and its receptors, creating a favorable environment for dopamine to influence GABA neuron migration. However, whether dopamine receptor activation can influence GABA neuron migration is not known. We show that dopamine D1 receptor activation promotes and D2 receptor activation decreases GABA neuron migration from the medial and caudal ganglionic eminences to the cerebral cortex in slice preparations of embryonic mouse forebrain. Slice preparations from D1 or D2 receptor knock-out mouse embryos confirm the findings. In addition, D1 receptor electroporation into cells of the basal forebrain and pharmacological activation of the receptor promote migration of the electroporated cells to the cerebral cortex. Analysis of GABA neuron numbers in the cerebral wall of the dopamine receptor knock-out mouse embryos further confirmed the effects of dopamine receptor activation on GABA neuron migration. Finally, dopamine receptor activation mobilizes striatal neuronal cytoskeleton in a manner consistent with the effects on neuronal migration. These data show that impairing the physiological balance between D1 and D2 receptors can alter GABA neuron migration from the basal forebrain to the cerebral cortex. The intimate relationship between dopamine and GABA neuron development revealed here may offer novel insights into developmental disorders such as schizophrenia, attention deficit or autism, and fetal cocaine exposure, all of which are associated with dopamine and GABA imbalance.
大脑皮层和其他端脑结构中的γ-氨基丁酸（GABA）能神经元在基底前脑产生，并在胚胎期迁移至其最终目的地。胚胎期的基底前脑富含多巴胺及其受体，为多巴胺影响GABA能神经元迁移创造了有利环境。然而，多巴胺受体激活是否能影响GABA能神经元迁移尚不清楚。我们发现，在胚胎小鼠前脑切片标本中，多巴胺D1受体激活促进、D2受体激活减少GABA能神经元从内侧和尾侧神经节隆起向大脑皮层的迁移。来自D1或D2受体基因敲除小鼠胚胎的切片标本证实了这一发现。此外，将D1受体电穿孔导入基底前脑细胞并对该受体进行药理学激活，可促进电穿孔细胞向大脑皮层迁移。对多巴胺受体基因敲除小鼠胚胎脑壁中GABA能神经元数量的分析进一步证实了多巴胺受体激活对GABA能神经元迁移的影响。最后，多巴胺受体激活以一种与对神经元迁移的影响相一致的方式动员纹状体神经元细胞骨架。这些数据表明，破坏D1和D2受体之间的生理平衡会改变GABA能神经元从基底前脑向大脑皮层的迁移。此处揭示的多巴胺与GABA能神经元发育之间的密切关系，可能为精神分裂症、注意力缺陷或自闭症等发育障碍以及胎儿可卡因暴露等提供新的见解，所有这些都与多巴胺和GABA失衡有关。
