Glutamate transporters prevent the generation of seizures in the developing rat neocortex.
Glutamate transporters are operative at an early developmental stage well before synapse formation, but their functional significance has not been determined. We now report that blockade of glutamate transporters in the immature neocortex generates recurrent NMDA receptor-mediated currents associated with synchronous oscillations of [Ca2+]i in the entire neuronal population. Intracerebroventricular injections of the blocker to pups generate seizures that are prevented by coinjections of NMDA receptor blockers. Therefore, the early expression of glutamate transporters plays a central role to prevent the activation by local glutamate concentrations of NMDA receptors and the generation of seizures that may alter the construction of cortical networks. A dysfunction of glutamate transporters may be a central event in early infancy epilepsy syndromes.
Demarque
Michael
M
Institut de Neurobiologie de la Méditerranée/Institut National de la Santé et de la Recherche Médicale U29, Parc Scientifique de Luminy, 13009 Marseille, France.
Villeneuve
Nathalie
N
Manent
Jean-Bernard
JB
Becq
Hélène
H
Represa
Alfonso
A
Ben-Ari
Yehezkel
Y
Aniksztejn
Laurent
L
D027322:Amino Acid Transport System X-AG / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000494:pharmacology; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D019579:Neocortex / Q000187:drug effects / Q000254:growth & development* / Q000503:physiopathology*; D009474:Neurons / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012640:Seizures / Q000503:physiopathology* / Q000517:prevention & control*
D027322:Amino Acid Transport System X-AG; D018690:Excitatory Amino Acid Agonists; D016194:Receptors, N-Methyl-D-Aspartate; C120673:benzyloxyaspartate; D001224:Aspartic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate