RT Journal Article SR Electronic T1 Estimating the glutamate transporter surface density in mouse hippocampal astrocytes JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.05.08.443234 DO 10.1101/2021.05.08.443234 A1 Anca R. Rădulescu A1 Cassandra L. Williams A1 Gabrielle C. Todd A1 Alex A. Lemus A1 Haley E. Chesbro A1 Annalisa Scimemi YR 2021 UL http://biorxiv.org/content/early/2021/05/10/2021.05.08.443234.abstract AB Glutamate transporters preserve the spatial specificity of synaptic transmission by limiting gluta-mate diffusion away from the synaptic cleft, and prevent excitotoxicity by keeping the extracellular concentration of glutamate at low nanomolar levels. Glutamate transporters are abundantly expressed in astrocytes. Previous estimates in the rat hippocampus suggest that the surface density of glutamate transporters in astrocytic membranes is ~ 10, 800 μm−2. Here, we estimate their surface density in astrocytic membranes of the mouse hippocampus, at different ages. By using realistic 3D Monte Carlo reaction-diffusion models, we show that varying the local glutamate transporter expression in astrocytes can alter profoundly the activation of extrasynaptic AMPA and NMDA receptors. Our findings show that the average density of astrocyte membranes and their surface density of glutamate transporters is higher in mice compared to rats, and increases with mouse age. There are stark differences in the density of expression of these molecules in different sub-cellular compartments, indicating that the extent to which astrocytes limit extrasynaptic glutamate diffusion depends not only on the level of astrocytic coverage, but also on the identity of the astrocyte compartment in contact with the synapse. Together, these findings provide information on the spatial distribution of glutamate transporters in the mouse hippocampus, which can be used in mathematical models of the spatiotemporal profile of extracellular glutamate after synaptic release.Main PointsThe astrocyte membrane density in the hippocampal neuropil is higher than in rats.The surface density of glutamate transporters in mouse astrocytes is higher than in rats and varies widely across different sub-cellular compartments.The identify of the astrocyte compartment in contact with a synapse, not only the extent of astrocytic coverage, is a main determinant of glutamate spillover and extrasynaptic receptor activation.Competing Interest StatementThe authors have declared no competing interest.