AbstractGlutamate is the major excitatory neurotransmitter in the mammalian nervous system. It is important that extracellular glutamate levels are kept low because glutamate can be toxic to neurons when present in high concentrations. Glutamate transporters remove glutamate from the extracellular space. There are five different glutamate transporters (excitatory amino acid transporters; EAATs), namely EAAT1 (GLAST), EAAT2 (GLT), EAAT3, EAAT4 and EAAT5. EAAT2 is quantitatively the most dominant transporter in the forebrain, and has previously only been detected in astrocytes in the normal and mature brain. Our group has observed that EAAT2 is also expressed in hippocampal nerve terminals, but at low densities compared to those in glial membranes. In spite of that, most of the uptake of D-aspartate (a non-metabolizeable EAAT substrate) is mediated by the fraction of EAAT2 present in nerve terminals. The aim of this study was to find the reason for this apparent mismatch between transporter distribution and uptake activity.