Accordingly, preventing MDGA1/Nlgn2 complex formation restored stress resilience in mice, as knocking out MDGA1 or introduction of an MDGA1 binding deficient variant of Nlgn2 increased both mIPSC frequency and GAD65 puncta within the LHb, which enhanced GABAergic synapse formation in the LHb and restored resistance to chronic stress-induced depression. Here, MDGA1 is linked to major depressive disorder.