Pharmacological inhibition of VPS34 activity suppressed NRBF2-dependent autophagy and AHN in the DG, which facilitated the susceptibility of mice to stress, while specific overexpression of NRBF2 in DG aNSCs ameliorated CSDS-induced AHN impairment and depression-like behavior via inducing autophagy. Here, PIK3C3 is linked to depressive disorder.