Neuronal migration during embryonic development contributes to functional brain circuitry. Many neurons migrate in morphologically distinct stages that coincide with differentiation, requiring tight spatial regulation. It had been proposed that neurotransmitter-mediated activity could exert this control. Here, we demonstrate that intracellular calcium transients occur in cerebellar neurons of zebrafish embryos during migration. We show that depolarization increases and hyperpolarization reduces the speed of tegmental hindbrain neurons using optogenetic tools and advanced track analysis optimized for in vivo migration. Finally, we introduce a compound screening assay to identify acetylcholine (ACh), glutamate, and glycine as regulators of migration, which act regionally along the neurons’ route. We summarize our findings in a model describing how different neurotransmitters spatially interact to control neuronal migration. The high evolutionary conservation of the cerebellum and hindbrain makes it likely that polarization state-driven motility constitutes an important principle in building a functional brain.

胚胎发育过程中的神经元迁移有助于大脑的功能电路。许多神经元以与分化相符的形态学上不同的阶段迁移，需要严格的空间调节。已经提出神经递质介导的活性可以发挥这种控制作用。在这里，我们证明了在迁移过程中斑马鱼胚胎的小脑神经元中发生细胞内钙瞬变。我们显示，使用光遗传学工具和针对体内迁移进行优化的高级轨迹分析，去极化增加，超极化减少后肢后脑神经元的速度。最后，我们介绍了一种化合物筛选试验，以鉴定乙酰胆碱（ACh），谷氨酸和甘氨酸作为迁移的调节剂，它们沿着神经元的路径在区域内起作用。我们在一个模型中总结了我们的发现，该模型描述了不同的神经递质如何在空间上相互作用以控制神经元迁移。小脑和后脑的高度进化保守性使得极化状态驱动的运动可能构成了构建功能性大脑的重要原理。