Murthy Sahana, Niquille Mathieu, Hurni Nicolas, Limoni Greta, Frazer Sarah, Chameau Pascal, van Hooft Johannes A, Vitalis Tania, Dayer Alexandre
1] Department of Mental Health and Psychiatry, University of Geneva Medical School, CH-1211 Geneva 4, Switzerland [2] Department of Basic Neurosciences, University of Geneva Medical School, CH-1211 Geneva 4, Switzerland.
Swammerdam Institute for Life Sciences, Center for NeuroScience, University of Amsterdam, Sciencepark 904, 1098 XH Amsterdam, The Netherlands.
Nat Commun. 2014 Nov 20;5:5524. doi: 10.1038/ncomms6524.
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-HT(3A)R) 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-HT(3A)R 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-HT(3A)R 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.
神经元兴奋性已被证明可控制源自尾侧神经节隆起（CGE）的表达reelin的皮质中间神经元（INs）的迁移和皮质整合，这支持了神经递质可能调节这一过程的可能性。在此，我们表明离子型5-羟色胺受体3A（5-HT(3A)R）在源自CGE的迁移中间神经元中特异性表达，并在它们侵入发育中的皮质时上调。使用钙成像、电生理记录和迁移试验进行的功能研究表明，源自CGE的INs在皮质板侵入后期增加了对5-HT(3A)R激活的反应。使用基因功能丧失方法和体内移植，我们进一步证明了5-HT(3A)R对于表达reelin的源自CGE的INs在新皮质中的迁移和正确定位是细胞自主所需的。我们的研究结果揭示了一种5-羟色胺受体在控制特定亚型皮质IN的迁移和层状定位中的必要性。
