Fig. 8

Schematic diagram illustrates extrasynaptic CaMKIIα and GluN2B in the hippocampus are involved in the antidepressant process of ketamine. LPS stimulation induces extrasynaptic CaMKIIα phosphorylation (p-CaMKIIα) and then binding to extrasynaptic GluN2B in the hippocampus, which causes extrasynaptic GluN2B retention and phosphorylation. The activation of extrasynaptic GluN2B downregulates p-CREB and BDNF levels and subsequently impairs LTP induction as well as induces synaptic protein deficits in the hippocampus, ultimately leading to depression-like behaviors. Ketamine administration reverses extrasynaptic CaMKIIα activation, followed by the normalization of extrasynaptic GluN2B localization and phosphorylation, which increases p-CREB, BDNF, and GluR1 levels in the hippocampus, and finally rescues depression-like behaviors