Glutamate transporters prevent the generation of seizures in the developing rat neocortex

被引:67
作者
Demarque, M [1 ]
Villeneuve, N [1 ]
Manent, JB [1 ]
Becq, H [1 ]
Represa, A [1 ]
Ben-Ari, Y [1 ]
Aniksztejn, L [1 ]
机构
[1] Inst Neurobiol Mediterranee, INSERM, U29, F-13009 Marseille, France
关键词
cortex; epilepsy; network; synchrony; transport; N-methyl-D-aspartate;
D O I
10.1523/JNEUROSCI.5338-03.2004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:3289 / 3294
页数:6
相关论文
共 34 条
[1]  
[Anonymous], 1991, ATLAS DEV RAT BRAIN
[2]   Cooperation between independent hippocampal synapses is controlled by glutamate uptake [J].
Arnth-Jensen, N ;
Jabaudon, D ;
Scanziani, M .
NATURE NEUROSCIENCE, 2002, 5 (04) :325-331
[3]   Glial cells and neurotransmission: An inclusive view of synaptic function [J].
Auld, DS ;
Robitaille, R .
NEURON, 2003, 40 (02) :389-400
[4]   Developing networks play a similar melody [J].
Ben-Ari, Y .
TRENDS IN NEUROSCIENCES, 2001, 24 (06) :353-360
[5]   THE FORMATION AND MATURATION OF SYNAPSES IN THE VISUAL-CORTEX OF THE RAT .1. QUALITATIVE-ANALYSIS [J].
BLUE, ME ;
PARNAVELAS, JG .
JOURNAL OF NEUROCYTOLOGY, 1983, 12 (04) :599-616
[6]   THE FORMATION AND MATURATION OF SYNAPSES IN THE VISUAL-CORTEX OF THE RAT .2. QUANTITATIVE-ANALYSIS [J].
BLUE, ME ;
PARNAVELAS, JG .
JOURNAL OF NEUROCYTOLOGY, 1983, 12 (04) :697-712
[7]   Increased expression of the neuronal glutamate transporter (EAAT3/EAAC1) in hippocampal and neocortical epilepsy [J].
Crino, PB ;
Jin, H ;
Shumate, MD ;
Robinson, MB ;
Coulter, DA ;
Brooks-Kayal, AR .
EPILEPSIA, 2002, 43 (03) :211-218
[8]   Glutamate uptake [J].
Danbolt, NC .
PROGRESS IN NEUROBIOLOGY, 2001, 65 (01) :1-105
[9]   Paracrine intercellular communication by a Ca2+- and SNARE-independent release of GABA and glutamate prior to synapse formation [J].
Demarque, M ;
Represa, A ;
Becq, H ;
Khalilov, I ;
Ben-Ari, Y ;
Aniksztejn, L .
NEURON, 2002, 36 (06) :1051-1061
[10]   Neuronal glutamate transporters limit activation of NMDA receptors by neurotransmitter spillover on CA1 pyramidal cells [J].
Diamond, JS .
JOURNAL OF NEUROSCIENCE, 2001, 21 (21) :8328-8338