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. 2017 Feb 1;37(5):1240–1256. doi: 10.1523/JNEUROSCI.2170-16.2016

Figure 1.

Figure 1.

nmdaLTP and vdccLTP show distinct profiles of sensitivity to MMP blockade. A, LTP in the CA3-CA1 pathway was induced by 200 Hz HFS (white). Two components that depend on the activation of NMDARs (nmdaLTP in the presence of 100 μm nifedipine, red) or L-type calcium channels (vdccLTP in the presence of 50 μm APV, gray) were pharmacologically identified. Insets, Representative average fEPSP traces recorded before (gray) and 115–120 min after (black) LTP. Calibration: vertical, 0.5 mV; horizontal, 5 ms. Stimulation artifacts were removed. The mean slope of fEPSPs that were recorded for 15 min before HFS was set at 100%. B, C, The MMP-2/MMP-9 inhibitor SB-3CT (10 μm) reduced the extent of both nmdaLTP (B) (CTR DMSO: 180 ± 18% of baseline 2 h after tetanus; SB-3CT: 132 ± 10%; t test, t(9) = 2.50, p = 0.034) and vdccLTP (C) (CTR DMSO: 169 ± 15%; SB-3CT: 130 ± 10%; t test, t(11) = 2.11, p = 0.047) induced by 200 Hz tetanus. D, The 200 Hz tetanus (delivered in the presence of 100 μm nifedipine) induced nmdaLTP that was similar in control conditions and in the presence of MMP inhibitor NNGH (10 μm, CTR DMSO: 140 ± 6%; NNGH: 141 ± 8%; t test, t(11) = −0.09, p = 0.93). E, Slowly developing L-type-dependent vdccLTP was induced by 200 Hz tetanus in the presence of 50 μm APV, which was impaired by the presence of NNGH (CTR DMSO: 145 ± 10%; NNGH: 107 ± 12%; Mann–Whitney U test, U(11) = 5.0, p = 0.022). F, Summary of the effects of pharmacological MMP inhibition with SB-3CT and NNGH on nmdaLTP and vdccLTP. The induction of vdccLTP, but not nmdaLTP, required MMP-3 activity. G, Extended TBS induced slowly developing vdccLTP when NMDARs were blocked by 50 μm APV (2 h after induction: 177 ± 12%). The inhibition of MMP-3 activity by NNGH (10 μm) abolished TBS-induced vdccLTP (NNGH: 112 ± 8%; t test, t(14) = 4.10, p = 0.001). H, Statistics for vdccLTP that was measured 115–120 min after stimulation. MMP-3 inhibition impaired TBS-induced vdccLTP similarly to vdccLTP that was induced by 200 Hz tetanus. Data are mean ± SEM. *p ≤ 0.05. ***p ≤ 0.001. n.s., not significant.