Although studies emphasized the role of the GluN2A and AKT signaling cascade in LPS-induced depression (Francija et al., 2018; Li et al., 2018), it remains open how Ephrin receptor signaling acts on NMDARs and AKT signaling contributes to decreased neuroplasticity and aberrant behavior upon LPS treatment. This evidence concerns the gene GRIN2A and depressive disorder.