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Nat Commun. 2014 Nov 20;5:5524. doi: 10.1038/ncomms6524.

Serotonin receptor 3A controls interneuron migration into the neocortex.

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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.
CNRS-UMR 8249, Brain Plasticity Unit, ESPCI ParisTech, 10 rue Vauquelin, 75005 Paris, France.


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.

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