Astrocytic group I mGluR dependent potentiation of astrocytic glutamate

34 One of the most important functions of astrocytes is removal of glutamate released 35 during synaptic transmission. Surprisingly, the mechanisms by which astrocyte 36 glutamate uptake is acutely modulated remain to be clarified. Astrocytes express 37 metabotropic glutamate and other G protein-coupled receptors (GPCRs) which are 38 activated during neuronal activity. Here we test the hypothesis that astrocytic group I 39 mGluRs acutely regulate glutamate uptake by astrocytes in situ. This hypothesis was 40 tested in acute mouse hippocampal slices. Activation of astrocytic mGluRs using a 41 tetanic high frequency stimulus (HFS) applied to Schaffer collaterals (SCs) led to 42 potentiation of the amplitude of the synaptically evoked glutamate transporter currents 43 (STCs) and associated charge transfer without changes in kinetics. Similar potentiation 44 of STCs was not observed in the presence of group I mGluR antagonists or the PKC 45 inhibitor, PKC 19-36, suggesting that HFS-induced potentiation of astrocyte glutamate 46 uptake is astrocytic group I mGluR and PKC dependent. Pharmacological stimulation of 47 a transgenic GPCR (MrgA1R) exclusively expressed in astrocytes also potentiated STC 48 amplitude and charge transfer, albeit quicker and shorter lasting compared to HFS49 induced potentiation. The amplitude of the slow inward astrocytic current due to 50 potassium influx was also enhanced following activation of either the endogenous 51 mGluRs or the astrocyte-specific MrgA1 Gq GPCRs. Taken together, these findings 52 suggest that astrocytic group I mGluR activation has a synergistic modulatory effect on 53 the uptake of both glutamate and potassium. 54 55