Ketamine-mediated synaptic potentiation occurs in the absence of activity but depends on protein synthesis and BDNF expression. A, Plotted are FP initial slopes after ketamine and TTX treatment as a function of time (mean ± SEM). Inset, Representative waveforms at different time points (1, 2). Synaptic strength increases significantly after treatment with ketamine plus TTX. One-way ANOVA with repeated measurements, F(23,167) = 6.16, p = 0.001; with Holm-Sidak post hoc test, p < 0.05; n = 7. Scale bar, 0.2 mV/5 ms. B, Input–output curves measured during baseline (1) and after ketamine plus TTX 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 plus TTX treatment is significantly different from the slope measured during baseline (t test, p = 0.01; n = 7). C, Plotted are FP initial slopes after TTX treatment as a function of time (mean ± SEM). Inset, Representative waveforms from TTX-treated slices at different time points (1, 2). There is no significant change in synaptic strength after application of TTX. Scale bar, 0.2 mV/5 ms; n = 5. D, Input–output curves measured during baseline (1) and after TTX 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). There is no significant change in the slope of input–output curve after application of TTX (n = 5). E, F, Application of anisomycin (20 μm) for the whole length of the experiment blocks synaptic potentiation induced by ketamine (n = 9) or MK801 (n = 5). Plotted are FP initial slopes as a function of time (mean ± SEM). Inset, Representative waveforms from ketamine-treated (E) and MK801-treated (F) slices at different time points (1, 2). G, H, Plotted are average values of FP initial slopes (mean ± SEM) measured during baseline at 30 min of ketamine and MK801 application and after 1 h of washout. Black bars (G) and white bars (H) are experiments from Fig. 1C,F (C, ketamine; F, MK801). Yellow bars, Ketamine or MK801 in presence of anisomycin (Fig. 2E,F). Scale bar, 0.2 mV/5 ms (G, n = 6; H, n = 5). Both ketamine and MK801 induce significant facilitation in synaptic strength, anisomycin abolishes this effect. I, In wild-type (WT) slices (n = 5), ketamine induced synaptic strength facilitation. In contrast, no changes were observed in slices from inducible BDNF knock-out mice after application of ketamine (n = 9). Plotted are FP initial slopes as a function of time (mean ± SEM). Inset, Representative waveforms from WT and inducible BDNF knock-out (KO) slices, recorded at different time points (1, 2). Synaptic strength increases significantly in WT ketamine-treated slices but not in slices from the BDNF KO. One-way ANOVA with repeated measurements, F(56,227) = 2.55, p = 0.001; with Holm-Sidak post hoc test, p < 0.05. Scale bar, 0.2 mV/5 ms.