In the nerve terminal, neurotransmitter is actively packaged into synaptic vesicles before its triggered release by Ca²⁺-dependent exocytosis. The three vesicular glutamate transporters (VGLUT1, -2 and –3) are highly conserved proteins that display similar bioenergetic and pharmacological properties but are expressed in different brain areas. While VGLUT1 and 2 territories represent the canonnical population of glutamatergic neurons, VGLUT3 is expressed in many populations of nonglutamatergic neurons. Indeed we could show that the expression of VGLUT3 at cholinergic, and serotonergic synaptic vesicles induce synergies between both uptakes of neurotransmitters in synaptic vesicles (vesicular synergy). Concomitently the expression of VGLUT3 at GABAergic synapses raises many questions.

Beyond vesicular synergy, VGLUTs have been found to bear more functions than the sole glutamate vesicular uptake. For instance, we mapped the interaction between VGLUT1 and EndophilinA1. This interaction was later shown to be responsible for a faster endocytosis of the corresponding vesicles and for a lowering of the release probability at VGLUT1 synapses. More recently, a debate arose from the possibility that VGLUTs could also function as Chloride channels. In such case scenario, VGLUTs would influence much more drastically the bioenergetics of synaptic vesicles than anticipated. As a consequence, many questions can be raised when the colocalisation of vésicular transporters is envisioned.