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. 2021 Apr 23;2021:6635084. doi: 10.1155/2021/6635084

Figure 6.

Figure 6

Ketamine-mediated lasting antidepressant effects result from NMDAR/CaMKII induced synaptic plasticity. A proposed model for the rapid and lasting actions of ketamine through the NMDAR/CaMKII pathway is presented. Administration of ketamine regulates calcium influx through its action on NMDAR resulting in rapid inhibition of CaMK2B phosphorylation and transcriptional stimulation of its inactive form. At the same time, ketamine promotes the dissociation of PSD95 from the NR2B/PSD95 complex in favor of newly formed CaMK2B/PSD95 complexes, leading to a significant stimulation of synaptic plasticity. In parallel, ketamine's regulation of intracellular calcium levels also leads to rapid phosphorylation of CaMK2A, further supporting the plasticity process through stimulation of plasticity-related proteins (PSD95). Overall, the results suggest that ketamine's temporary regulation of the NMDAR/CaMKII pathway not only accounts for its rapid actions but also initiates profound and lasting changes (<a week) at the postsynaptic level leading to its lasting antidepressant effects. The illustration was partially based on motifs from http://motifolio.com.