Central nervous system neurons have traditionally been thought to express exclusively membrane transporters and/or vesicular transporters for their transmitter. Three vesicular glutamate transporters (VGLUTs) have been cloned: BNPI/VGLUT1 (a brain-specific sodium dependent inorganic phosphate (Pi) transporter), and its homologs DNPI/VGLUT2 (differentiation-associated sodium-dependent Pi transporter) and VGLUT3¹. These transporters mediate glutamate uptake inside presynaptic vesicles and are anatomical and functional markers of glutamatergic excitatory transmission².

BNPI/DNPI encodes a membrane protein with 6-8 putative transmembrane domains which exhibits weak similarities to a kidney Na⁺-dependent inorganic phosphate co-transporter³. The transporters use a membrane potential gradient set by the vesicular H⁺-ATPase for glutamate uptake⁴. VGLUT1-3 are very similar in structure and function, but are used by different neuronal populations. VGLUT1 and VGLUT2 are expressed by the cortical and subcortical neurons respectively. VGLUT3 is expressed by non-glutamatergic neurons⁵. VGLUT2 is expressed in the thalamus, brainstem, and deep cerebellar nuclei². A Recent study has shown that  targeted deletion of VGLUT2 in mice causes perinatal lethality and a 95% reduction in evoked glutamatergic responses in thalamic neurons, although hippocampal synapses function normally. Behavioral analysis of heterozygous VGLUT2 mice showed discrete behavioral phenotypes that suggest a deficit in thalamic processing⁶.