title: A noncanonical release of GABA and glutamate modulates neuronal migration.
abstract: Immature neurons express GABA and glutamate receptors before synapse formation, and both transmitters are released at an early developmental stage. We have now tested the hypothesis that the ongoing release of GABA and glutamate modulates neuronal migration. Using 5-bromo-2'-deoxyuridine labeling and cocultures of hippocampal slices obtained from naive and green fluorescent protein-transgenic mice, we report that migration is severely affected by GABA(A) or NMDA receptor antagonist treatments. These effects were also present in munc18-1 knock-out slices in which soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-dependent vesicular secretion of transmitters has been deleted. GABA(A) antagonists were more efficient than NMDA antagonists to reduce cell migration, in keeping with the earlier maturation of GABAergic mechanisms. We conclude that GABA and, to a lesser degree, glutamate released in a SNARE-independent mechanism exert a paracrine action on neuronal migration.
authors.affiliation: Institut de Neurobiologie de la Méditerranée, Institut National de la Santé et de la Recherche Médicale U29, Campus de Luminy BP13, 13273 Marseille, France.
authors.forename: Jean-Bernard
authors.initials: JB
authors.lastname: Manent
authors.forename: Michaël
authors.initials: M
authors.lastname: Demarque
authors.forename: Isabel
authors.initials: I
authors.lastname: Jorquera
authors.forename: Christophe
authors.initials: C
authors.lastname: Pellegrino
authors.forename: Yehezkel
authors.initials: Y
authors.lastname: Ben-Ari
authors.forename: Laurent
authors.initials: L
authors.lastname: Aniksztejn
authors.forename: Alfonso
authors.initials: A
authors.lastname: Represa
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D015224:Dideoxynucleosides / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004622:Embryo, Mammalian; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D051938:Munc18 Proteins / Q000235:genetics; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D015763:2-Amino-5-phosphonovalerate; D001640:Bicuculline; D001973:Bromodeoxyuridine; D015224:Dideoxynucleosides; D016291:Dizocilpine Maleate; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018698:Glutamic Acid; D049452:Green Fluorescent Proteins; D008869:Microtubule-Associated Proteins; D051938:Munc18 Proteins; D016202:N-Methylaspartate; D010852:Picrotoxin; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D005680:gamma-Aminobutyric Acid; C489787:MAP2 protein, rat; C073006:5-bromo-2',3'-dideoxyuridine