Serotonin receptor 3A controls interneuron migration into the neocortex

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Cell Movement / genetics*
  • Extracellular Matrix Proteins / metabolism
  • Gene Expression Regulation, Developmental / genetics*
  • Interneurons / metabolism*
  • Mice
  • Neocortex / embryology
  • Neocortex / metabolism*
  • Nerve Tissue Proteins / metabolism
  • Receptors, Serotonin, 5-HT3 / genetics*
  • Reelin Protein
  • Serine Endopeptidases / metabolism


  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Htr3a protein, mouse
  • Nerve Tissue Proteins
  • Receptors, Serotonin, 5-HT3
  • Reelin Protein
  • Reln protein, mouse
  • Serine Endopeptidases