Glutamate is the major neurotransmitter of CNS. Before its exocytotic release in the synaptic cleft, glutamate is loaded into synaptic vesicles by three transporters named VGLUT1-3. In the rodent brain, VGLUT1-3 are distributed in three complementary glutamatergic systems showing little overlap. VGLUT1 is essentially cortical, VGLUT2 subcortical and VGLUT3 is present in neurons using other transmitters than glutamate (cholinergic interneurons from the striatum, GABAergic interneurons from the hippocampus and cortex and serotonergic neurons). The three VGLUTs are the first available specific markers of glutamatergic neurons and terminals. These proton-dependent carriers share a high degree of structural and functional homology.
The strength of synaptic transmission is controlled both at the pre- and post-synaptic levels. Vesicular glutamate transporters play an essential role in glutamatergic transmission. Indeed, recent studies have documented that the concentration of vesicular transporters directly impacts on the strength of synaptic transmission.