FIG. 5.

Proteolytically active MMP-9 induces potentiation in rat area CA1 in vivo that occludes, and is occluded by, tetanic stimulation. A: recombinant active MMP-9 (rMMP-9; 0.1 μg/μl) delivered intrahippocampally (bar) induces a slowly emerging, persistent potentiation that begins to arise approximately 60 min postinjection (●, n = 5). Administration of inactive pro-MMP-9 (▲) or recombinant active MMP-2 (rMMP-2; ◆) did not elicit an increase in fEPSP slope (n = 3 each). Inset: representative EPSP traces were recorded before (1), 90 min after rMMP-9 application (2), and 90 min after rMMP-2 application (3). Calibration: 10 ms, 0.3 mV. B: intrahippocampal infusion of rMMP-9 has no effect on PPF. Plot shows PPF measured before (●) and 120 min after (○) rMMP-9 administration. Inset: representative EPSP traces (50 ms IPI) recorded before and after rMMP-9 injection. Calibration: 25 ms, 0.2 mV. C: rMMP-9 potentiation occludes tetanically-induced potentiation. After rMMP-9 potentiation reached a plateau (~90 min), fEPSP slope was reduced to yield synaptic responses that matched those of baseline levels, followed by tetanic stimulation (↑). There was no further potentation after tetanic stimulation (●). The ghostline (○) indicates the level of tetantically induced LTP in control animals (see Fig. 1A). Representative EPSP traces were recorded at time points indicated in the panel. D: tetanic stimulation occludes rMMP-9 potentiation. Tetanic stimulation (↑) produces LTP (●); at ~45 min postinduction, stimulus intensity was reduced to produce synaptic responses that matched those of the original baseline, followed by administration of rMMP-9 (bar). There was no further potentiation following delivery of rMMP-9 (●). The ghostline (○) indicates the level of rMMP-9-induced potentiation from animals shown in A. Representative EPSP traces were recorded at time points indicated in the panel. Calibration as in Fig. 1A.