Acute suppression of spontaneous neurotransmission drives synaptic potentiation - PubMed (original) (raw)

Ketamine application at rest potentiates subsequent AMPAR-mediated evoked neurotransmission. A, FPs were recorded in control (n = 6) and ketamine-treated (20 μ

) (n = 12) slices. Initial FP slopes are plotted as a function of time (mean ± SEM). Inset, Representative waveforms from control and ketamine-treated slices recorded at different time points (1, 2). The line with the asterisk indicates the area of significant change. One-way ANOVA with repeated measurements, F(121,853) = 2.4, p = 0.001; with Holm-Sidak post hoc test, p < 0.05. Scale bar, 0.2 mV/5 ms. B, Left, NMDAR FPs as a function of time (mean ± SEM). Ketamine was applied after baseline for 30 min at rest, followed with a train of 200 stimuli at 1 Hz, and 20 stimuli at 20 Hz, in the presence of ketamine (n = 6). NMDAR FPs were recorded in solution containing the following: 124 m

NaCl, 2 m

KCl, 3 m

CaCl2, 0.1 m

MgCl2, 10 m

glucose, 1.2 m

NaH2PO4, 26 m

NaHCO3, 10 μ

glycine, 20 μ

DNQX, 50 μ

picrotoxin. Right, Representative traces of NMDAR FP recorded during baseline (1), at the end of 1 Hz train (2), and during 20 Hz stimulation (3). C, Different protocol of ketamine application (see Materials and Methods). FP initial slopes from control (n = 5) and ketamine-treated slices (n = 9) are plotted as a function of time (mean ± SEM). Inset, Representative waveforms from ketamine-treated slices at different time points (1, 2). Synaptic strength increases significantly in ketamine-treated slices, compared with control slices. One-way ANOVA with repeated measurements, F(10,65) = 7.3, p = 0.001; with Holm-Sidak post hoc test, p < 0.05. Scale bar, 0.2 mV/5 ms. D, Paired-pulse facilitation. Plotted are FP2/FP1 ratios recorded during baseline (1) and after ketamine application (2) as a function of ISI (mean ± SEM). Inset, Representative traces: 0 FP1 followed by FP2 with 20, 50, 200, and 500 ms ISI. No significant changes were observed in these experiments (n = 9). Scale bar, 0.2 mV/5 ms. E, Input–output curves measured during baseline (1) and after ketamine washout (2). Plotted are FP initial slopes (mean ± SEM) as a function of presynaptic volley values at 5, 10, 15, 20, and 25 μA stimulation intensity. The slope of the input–output curve after ketamine treatment (2) is significantly different from the slope measured during baseline (1); (t test, p < 0.05) (n = 9). Inset, Representative FP trace. F, Plotted are FP initial slopes (mean ± SEM) from control slices (n = 5) and slices treated with 10 μ

MK801 (n = 5) as a function of time. Inset, Representative waveforms from MK801-treated slices at different time points (1, 2). Synaptic strength increases significantly in MK801-treated slices while no changes are observed in control slices (Control no drug). One-way ANOVA with repeated measurements, F(37,151) = 2.75, p = 0.001; with Holm-Sidak post hoc test, p < 0.05. Scale bar, 0.2 mV/5 ms. G, FPs elicited by paired-pulse stimulation with ISI of 20, 30, 50, 100, 200, 300, 400, and 500 ms during the baseline (open circles) and after MK801 washout (open squares). Plotted are FP2/FP1 ratios (± SEM) as a function of interpulse interval. Inset, Representative traces: 0 FP1 followed by FP2 with 20, 50, 200, and 500 ISI. No significant changes were observed in these experiments (n = 5). Scale bar, 0.2 mV/5 ms. H, Input–output curves measured during baseline (1) and after MK801 washout (2). Plotted are FP initial slopes as a function of presynaptic volley values (mean ± SEM) at 5, 10, 15, 20, and 25 μA stimulation intensity. The slope of input–output curve after MK801 treatment is significantly different from the slope without MK801 treatment (t test, p = 0.02; n = 5). Inset, Representative FP trace. I, Left, Plotted are NMDAR FP initial slopes before and after ketamine treatment as a function of time (mean ± SEM). After application of ketamine and 1 h washout, no significant changes in synaptic strength were observed. One-way ANOVA with repeated measurements, F(1,60) = 14.1, p = 0.4 (n = 5). Right, Representative traces of NMDAR FP recorded at different time points (1, 2, 3). J, Input–output curves for NMDAR FP measured during baseline (1) and after ketamine washout (3). Plotted are FP initial slopes as a function of presynaptic volley values (mean ± SEM) at 10, 20, 30, and 40 μA stimulation intensity. There is no significant change in the slope of input–output curves before and after ketamine treatment (p = 0.44; n = 5).