HCRT and major depressive disorder: Since GABAergic neurons are the majority of neurons in VP and these principle neurons distributed across whole VP project to various brain regions related to depression, such as the lateral habenula and medial dorsal nuclei of thalamus [10, 50], our results suggest that orexinergic inputs widespread throughout the VP may prevent multiple depressive symptom domains via direct modulation on GABAergic neurons in both anterior and posterior VP, and VP may be an essential target of orexin and orexinergic system for protection against depression.