EPHB2 and major depressive disorder: It was demonstrated that NMDARs regulated several downstream signal transduction pathways correlated to the synaptic plasticity of depression (e.g., cAMP-PKA, RAS-ERK, MAPK, and PI3K-AKT) (Yoshii and Constantine-Paton, 2010; Marsden, 2013; Leal et al., 2014).