Kim et al. (2012) further observed that rats infused with lentiviral shRNA-HCN1 in the dorsal hippocampal CA1 region displayed antidepressant- and anxiolytic-like behaviors associated with widespread enhancement of hippocampal activity. Similar result was also confirmed in CUS, a widely accepted model for major depressive disorder. Deletion of HCN1 by shRNA-HCN1 in the dorsal CA1 region prevented the CUS-induced behavioral deficits (Kim et al., 2018). This evidence concerns the gene HCN1 and major depressive disorder.