The conversion of glutamate by glutamine synthase in neocortical astrocytes from juvenile rat is important to limit glutamate spillover and peri/extrasynaptic activation of NMDA receptors

Yosra Trabelsi , Mohamed Amri (1) , Hélène Becq (2, 3, 4) , Florence Molinari (2, 3, 4) , Laurent Aniksztejn (5, 2, 3, 4)

1 UTM - Université de Tunis El Manar
2 AMU - Aix Marseille Université
3 INMED - INSERM U901 - Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université]
4 INSERM - Institut National de la Santé et de la Recherche Médicale
5 Epilepsie et ischémie cérébrale

Glutamate transporters (EAATs) are important to maintain spatial and temporal specificity of synaptic transmission. Their efficiency to uptake and transport glutamate into the intracellular space depends on several parameters including the intracellu-lar concentrations of Na 1 and glutamate, the elevations of which may slow down the cycling rate of EAATs. In astrocytes, glutamate is maintained at low concentration due to the presence of specific enzymes such as glutamine synthase (GS). GS inhibition results in cytosolic accumulation of glutamate suggesting that the conversion of glutamate by GS is important for EAATs operation. Here we recorded astrocytes from juvenile rat neocortical slices and analyzed the consequences of elevated intracellular glutamate concentrations and of GS inhibition on the time course of synaptically evoked transporter current (STC). In slices from rats treated with methionine sulfoximine (MSO), a GS inhibitor, STC evoked by short burst of high frequency stimulation (HFS; 100 Hz for 100 ms) but not by low frequency stimulation (LFS; 0.1 Hz) was twice slower than STC evoked from saline injected rats. Same results were obtained for astrocytes recorded with pipette containing 3-10 mM gluta-mate and compared with cells recorded with 0 or1 mM glutamate in the patch pipette. We also showed that HFS elicited significantly larger NMDAR-excitatory postsynaptic currents (EPSCs) with a stronger peri/extrasynaptic component in pyramidal cells from MSO-treated compared with saline treated rats. Taken together our data demonstrate that the conversion of gluta-mate by GS is fundamental to ensure an efficient clearance of glutamate by EAATs and to prevent glutamate spillover. GLIA 2016;00:000-000

Mots clés: glutamate spillover; neocortex; methio-nine sulfoximine; NMDA receptors; astrocytes; glutamine synthase; glutamate transporters

Domaines: Neurosciences [q-bio.NC]

Yosra Trabelsi, Mohamed Amri, Hélène Becq, Florence Molinari, Laurent Aniksztejn. The conversion of glutamate by glutamine synthase in neocortical astrocytes from juvenile rat is important to limit glutamate spillover and peri/extrasynaptic activation of NMDA receptors. Glia, 2017, 65 (2), pp.401-415. ⟨10.1002/glia.23099⟩. ⟨hal-01962551⟩