NMDA Receptor-Dependent Metaplasticity by High-Frequency Magnetic Stimulation

Figure 3

LTP reduction caused by HFMS priming is NMDA receptor-dependent. (A1) Experimental paradigm showing the timepoints of high-frequency magnetic stimulation (HFMS) and conditioning stimulation (CS). Application of the NMDA receptor blocker D-AP5 is indicated by the gray bar. (A2) Sample traces of timepoints ①, ②, and ④ in naive (control) and HFMS-primed slices. (A3) Time course of CS-induced plasticity with (closed circles) or without (open circles) priming. HFMS priming was applied following baseline recording. The enhanced fEPSPs by HFMS priming were readjusted to baseline level before electrical stimulation (CS). HFMS caused a significant reduction of CS-induced LTP. (A4) Average fEPSP slopes calculated during 26–30 and 96–100 min after HFMS application. Significant LTP was induced after CS in control slices without priming stimulation (open bar). In contrast, the level of CS-induced LTP in HFMS-primed slices was significantly reduced compared to slices without priming stimulation. Note that HFMS-induced potentiation and CS-induced potentiation were not significantly different. (B1) Sample traces of timepoints ① and ④ in naive (control) and HFMS-primed slices under NMDA receptor-blocking conditions. (B2) Time course of CS-induced plasticity with (closed circles) or without (open circles) priming. HFMS priming was applied in the presence of the NMDA receptor antagonist D-AP5 (50 μM). The slightly enhanced fEPSPs following HFMS priming were readjusted to baseline level before electrical CS. D-AP5 was washed out after HFMS in order to allow NMDA receptor-dependent CS-induced LTP. (B3) Average fEPSP slopes calculated during 26–30 and 96–100 min after HFMS application. In contrast to panel (A4), the levels of CS-induced LTP were no longer different between HFMS-primed or unprimed slices.

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