Cai et al. demonstrated that astrocytes are a direct insulin target in the brain and that knock-out of the insulin receptor on astrocytes caused increased anxiety-like and depression-like behaviors in mice; they also showed that loss of insulin signaling in astrocytes impaired tyrosine phosphorylation of Munc18c, which leads to decreased exocytosis of ATP from astrocytes, which in turn causes decreased purinergic signaling on dopaminergic neurons [31]. Here, INS is linked to depressive disorder.