In the rat model of depression induced by CUMS, the levels of NMDAR phosphorylation and subunit NR1/NR2B protein increased significantly, the abnormal concentration of Glu in synaptic space led to the overactivation of extra synaptic NMDAR, and a large amount of Ca2+ influx led to intracellular Ca2+ overload, resulting in nerve cell death (Li et al., 2018; Beneyto et al., 2007). Here, GRIN1 is linked to major depressive disorder.