Ketamine-mediated synaptic potentiation requires eEF2 kinase activity. A, D, Plotted are FP initial slopes as a function of time (mean ± SEM) from wild-type (WT) (n = 6) and eEF2K knock-out (KO) (n = 7) mice slices treated with ketamine. Inset, Representative waveforms from ketamine-treated slices during different time points (1, 2). Synaptic strength increases significantly in ketamine-treated slices from WT mice, but not in eEF2K KO mice. One-way ANOVA with repeated measurements, F(16,101) = 10.9, p = 0.001; with Holm-Sidak post hoc test, p < 0.05. Scale bar, 0.2 mV/5 ms. B, E, Paired-pulse facilitation. FPs elicited by paired-pulse stimulation in slices from WT and eEF2K KO mice, during the baseline (1) and after ketamine washout (2). Plotted are FP2/FP1 ratios as a function of ISI (mean ± SEM). No significant changes were observed in these experiments. Scale bar, 0.2 mV/5 ms. C, F, Input–output curves measured in slices from WT and eEF2K KO mice during baseline (1) and after ketamine washout (2). Plotted are FP initial slopes as a function of presynaptic volley values at 5, 10, 15, 20, and 25 μA stimulation intensity (mean ± SEM). The slope of input–output curve after ketamine treatment of WT slices increases significantly (C) (t test, p = 0.009). In the case of eEF2K KO, there is no change in the slope of input–output curve (F).