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. Author manuscript; available in PMC: 2021 Apr 6.
Published in final edited form as: Behav Brain Res. 2020 Feb 2;383:112532. doi: 10.1016/j.bbr.2020.112532

Figure 1:

Figure 1:

(A) Ketamine blockade of NMDA receptors onto GABAergic interneurons decreases GABAergic tone onto glutamatergic neurons, thereby causing glutamatergic neuronal activation (“disinhibition hypothesis”) and glutamate release. (B) Glutamate -induced AMPA receptor activation leads to activity-dependent Brain Derived Neurotrophic Factor (BDNF) release, with consequently activation of the BDNF receptor, TrKB, and a downstream signaling activation that is linked to synaptogenesis. (C) ketamine blockade of NMDA receptors that are normally activated by spontaneous, rather than evoked glutamate release, causes phosphorylation of CamKII (pCamKII) and inhibition of the elongation factor 2 kinase (eEF2K). The inhibition of eEF2K decreases the levels of the phosphorylated form of the elongation factor 2 (peEF2). Both decreases in peEF2 and increases in pCamKII are associated with increased protein translation. (D) Negative allosteric modulators of α5-containing GABAA receptors (NAM) causes depolarization and activity-dependent glutamate release. (E) Positive allosteric modulator of the α5-containing GABAA receptors (PAM) causes hyperporalization.