The department of Physiology welcomes Lisa Monteggia, Ph.D.
Clinical studies have demonstrated that a single subpsychotomimetic dose of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, produces rapid antidepressant responses in patients with major depressive disorder. Data will be presented showing that ketamine mediated blockade of NMDA receptors at rest targets a specific signaling cascade that involves deactivation of eukaryotic elongation factor 2 (eEF2) kinase, resulting in reduced eEF2 phosphorylation and desuppression of rapid dendritic protein translation, including BDNF, which then contributes to synaptic plasticity mechanisms. These findings identify critical determinants of how blocking spontaneous neurotransmission impacts synaptic plasticity with implications for ketamine mediated antidepressant responses.