Serotonin receptor 3A controls interneuron migration into the neocortex.

Serotonin receptor 3A controls interneuron migration into the neocortex.
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5-羟色胺受体3A控制中间神经元迁移到新皮层。

DOI:
10.1038/ncomms6524
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发表时间:
2014-11-20
影响因子:
16.6
通讯作者:
Dayer, Alexandre
Dayer, Alexandre
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Murthy, Sahana;Niquille, Mathieu;Hurni, Nicolas;Limoni, Greta;Frazer, Sarah;Chameau, Pascal;van Hooft, Johannes A.;Vitalis, Tania;Dayer, Alexandre

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神经元的兴奋性已被证明可以控制从尾神经节隆起(CGE)产生的表达reelin的皮质中间神经元(IN)的迁移和皮质整合,支持神经递质可以调节这一过程的可能性。在这里,我们表明,离子型5-羟色胺受体3A(5-HT 3AR)是特异性表达的CGE衍生的迁移的中间神经元和上调,而他们侵入发展中的皮层。使用钙成像,电生理记录和迁移试验的功能研究表明,CGE衍生的INs增加他们的反应,5-HT 3AR激活在皮质板入侵的后期。使用遗传功能丧失的方法和体内移植物,我们进一步证明,5-HT 3AR是细胞自主需要的迁移和正确定位的reelin表达的CGE衍生的INs在新皮层。我们的研究结果揭示了在控制特定亚型的皮质IN的迁移和层状定位中对5-羟色胺受体的需求。 在大脑发育过程中,神经元的兴奋性控制皮质中间神经元从尾神经节隆起(CGE)的层状迁移。在这里,作者将5-HT 3A受体确定为CGE衍生的皮质中间神经元(CIN)的特异性标记物,并作为CIN迁移的刺激物。
Neuronal excitability has been shown to control the migration and cortical integration of reelin-expressing cortical interneurons (INs) arising from the caudal ganglionic eminence (CGE), supporting the possibility that neurotransmitters could regulate this process. Here we show that the ionotropic serotonin receptor 3A (5-HT3AR) is specifically expressed in CGE-derived migrating interneurons and upregulated while they invade the developing cortex. Functional investigations using calcium imaging, electrophysiological recordings and migration assays indicate that CGE-derived INs increase their response to 5-HT3AR activation during the late phase of cortical plate invasion. Using genetic loss-of-function approaches and in vivo grafts, we further demonstrate that the 5-HT3AR is cell autonomously required for the migration and proper positioning of reelin-expressing CGE-derived INs in the neocortex. Our findings reveal a requirement for a serotonin receptor in controlling the migration and laminar positioning of a specific subtype of cortical IN. During brain development, neuronal excitability controls the laminar migration of cortical interneurons from the caudal ganglionic eminences (CGEs). Here the authors identify the 5-HT3A receptor as a specific marker of CGE-derived cortical interneurons (cINs), and as a stimulator of cIN migration.
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