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The Journal of Neuroscience, March 31, 2004, 24(13):3289-3294; doi:10.1523/JNEUROSCI.5338-03.2004

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BRIEF COMMUNICATION
Glutamate Transporters Prevent the Generation of Seizures in the Developing Rat Neocortex

Michael Demarque, Nathalie Villeneuve, Jean-Bernard Manent, Hélène Becq, Alfonso Represa, Yehezkel Ben-Ari, and Laurent Aniksztejn

Institut de Neurobiologie de la Méditerranée/Institut National de la Santé et de la Recherche Médicale U29, Parc Scientifique de Luminy, 13009 Marseille, France

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.

Key words: cortex; epilepsy; network; synchrony; transport; N-methyl-D-aspartate

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Received Dec 3, 2003; revised January 12, 2004; accepted January 28, 2004.

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