Serotonergic Projections Govern Postnatal Neuroblast Migration
Serotonergic Projections Govern Postnatal Neuroblast Migration
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DOI：
10.1016/j.neuron.2017.04.013
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发表时间：
2017-05-03
期刊：
影响因子：
16.2
通讯作者：
Monyer, Hannah
中科院分区：
文献类型：
--
作者：
Garcia-Gonzalez, Diego;Khodosevich, Konstantin;Monyer, Hannah
在许多脊椎动物中，出生后产生的神经元通常会迁移很长的距离到达它们的最终目的地，在那里它们有助于塑造局部电路活动。需要外部刺激的协调作用来调节长距离迁移。一些迁移原则是进化上保守的，而另一些则是物种和细胞类型特异性的。在这里，我们确定了一个多巴胺能机制，管理出生后产生的神经元在小鼠大脑中的迁移。起源于中缝核的5-羟色胺能轴突与室管膜下区来源的成神经细胞表现出明显的一致性。光生轴突激活为成神经细胞迁移的多巴胺能调节提供了功能证据。此外，我们表明，潜在的机制涉及5-羟色胺受体3A（5 HT 3A）介导的钙内流。因此，5 HT 3A受体缺失的神经母细胞损害的速度和方向性的迁移和废除钙尖峰。我们推测，在其他脊椎动物的迁移路径中存在的神经元轴突的存在下，出生后产生的成神经细胞迁移的神经元调节是进化保守的。
In many vertebrates, postnatally generated neurons often migrate long distances to reach their final destination, where they help shape local circuit activity. Concerted action of extrinsic stimuli is required to regulate long-distance migration. Some migratory principles are evolutionarily conserved, whereas others are species and cell type specific. Here we identified a serotonergic mechanism that governs migration of postnatally generated neurons in the mouse brain. Serotonergic axons originating from the raphe nuclei exhibit a conspicuous alignment with subventricular zone-derived neuroblasts. Optogenetic axonal activation provides functional evidence for serotonergic modulation of neuroblast migration. Furthermore, we show that the underlying mechanism involves serotonin receptor 3A (5HT3A)-mediated calcium influx. Thus, 5HT3A receptor deletion in neuroblasts impaired speed and directionality of migration and abolished calcium spikes. We speculate that serotonergic modulation of postnatally generated neuroblast migration is evolutionarily conserved as indicated by the presence of serotonergic axons in migratory paths in other vertebrates.