LTP at mossy fiber–perisomatic inhibitory interneuron synapses is NMDA receptor independent but requires AMPA receptor activation. A, Left, Individual peak amplitudes of AMPAR-mediated EPSCs elicited at MF–PII synapses in the presence of the NMDAR blocker d-APV plotted as a function of time before and after pairing for a single PII. The arrow indicates the time of BFS application. Right, LTP in the presence of d-APV (50 μm; black circles) is expressed to the same extent (175.8 ± 27.8% at 15–20 min after pairing; 5 cells) as in the absence of d-APV (red circles; 166.4 ± 25.7%; p = 0.241; same data as in Fig. 3B), demonstrating that LTP at MF–PII synapses is not NMDAR dependent. B, Block of AMPARs at MF–PII synapses prevents LTP. Left, Amplitudes of individual EPSCs are plotted as a function of time for two independent MF inputs to a single PII. After a baseline period, 10 μm CNQX was washed in to block AMPARs (Vhold = −70 mV; amplitude reduction, ∼85%). A BFS was applied to one MF input (red circles) at t = 0 (arrow). Washout of CNQX was started immediately after the pairing protocol. Time course of recovery of the paired MF input (red circles) and the unpaired MF input (black circles) was similar indicating that LTP was not induced. Inset, Average EPSCs during the control period (1), first 30 s after the pairing (2), and at late phases after LTP induction (15–20 min). Right, Summary of the experimental data from eight cells. Each circle represents the average of EPSCs over 30 s intervals for the paired (black) and control MF input (red) normalized to the mean baseline amplitudes. The gray bars indicate the duration of the CNQX wash-in; the vertical dashed lines refer to the time of the BFS. A, Two-tailed Student's t test. B, Wilcoxon's signed rank test. Average measurements represent mean ± SEM.