In the hippocampus, VGLUT3 was shown to modulate 5-HTergic tone, and to stimulate VMAT2-dependent accumulation of 5-HT in synaptic vesicles (Amilhon et al., 2010), which further suggests that VGLUT3/5-HT synaptic cross-talk may play an important role in hippocampal-mediated behaviors such as anxiety and depression. This evidence concerns the gene SLC18A2 and major depressive disorder.