Glutamate acting on AMPA but not NMDA receptors modulates the migration of hippocampal interneurons.
Paracrine GABA and glutamate acting, respectively, on GABAA and NMDA receptors modulate the migration of hippocampal pyramidal cells. Using corticohippocampal organotypic explants from glutamic acid decarboxylase (GAD) 67-enhanced green fluorescent protein (EGFP) knock-in embryos, we now report that, in contrast to pyramidal neurons, the blockade of AMPA but not NMDA receptors exerts important actions on the migration of GABAergic interneurons. In addition, the blockade of GABAA receptors fails to modify the migration rates of GABAergic interneurons. Immunohistochemical analyses of GAD67-EGFP embryos (from embryonic day 14 to birth) reveal that interneurons colonize the hippocampal primordium by embryonic day 15. At that stage, the hippocampal primordium is already composed of pioneer glutamatergic neurons, including (1) Cajal-Retzius cells, immunopositive to calretinin and reelin, and (2) other presumptive pioneer pyramidal cells that are immunopositive to betaIII-tubulin and vesicular glutamate transporter 3 and immunonegative to GABA or GAD67. Therefore, the migrations of pyramidal neurons and GABAergic interneurons are cross-modulated: glutamate released from pioneer glutamatergic neurons facilitates the migration of GABAergic interneurons, which in turn would release GABA, facilitating the migration of glutamatergic neuroblasts. This general sequence may provide a retroactive positive loop needed to construct the hippocampal network. It might constitute a primitive homeostatic mechanism in the developing brain that acts to balance GABA-glutamate contributions to network construction and activity.
Manent
Jean-Bernard
JB
Institut de Neurobiologie de la Méditerranée, Institut National de la Santé et de la Recherche Médicale, Unité 29, 13273 Marseille, France.
Jorquera
Isabel
I
Ben-Ari
Yehezkel
Y
Aniksztejn
Laurent
L
Represa
Alfonso
A
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000196:embryology / Q000502:physiology; D047108:Embryonic Development; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects / Q000196:embryology* / Q000502:physiology*; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D018091:Receptors, AMPA / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D000091042:Reelin Protein
D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D000091042:Reelin Protein; D049452:Green Fluorescent Proteins; D018698:Glutamic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C000717128:Reln protein, mouse