Figure 6. Metaplasticity cannot be induced in NesCreIrs2KO mice also under conditions that enhance NMDA receptor activity.

A: A priming stimulus (5 Hz; small arrow) applied 20 min prior to TBS (large arrow) induced further metaplasticity in control mice (+/+) (5 Hz primed, 60 min post TBS; average EPSP slope change: 113±3%, N = 3, n = 5) compared with the un-primed values (Un-primed, 60 min post TBS; average EPSP slope change: 135±3%, N = 5, n = 6; p<0.00002), in the presence of 1 mM extracellular Mg²⁺ and 3 mM extracellular Ca²⁺ to enhance NMDA receptor activity. B: The same priming protocol did not significantly alter TBS-induced LTP in NesCreIrs2KO mice (−/−) (5 Hz primed, 60 min post TBS; average EPSP slope change: 120±6%, N = 3, n = 5) when compared to un-primed values recorded 60 min following induction (Un-primed, 60 min post TBS; average EPSP slope change: 127±4, N = 4, n = 5). Insets in A and B show representative EPSP traces (average of 4 consecutive sweeps) taken prior to and 60 min post-LTP induction. These traces are taken from individual experiments in control (A; +/+) and NesCreIrs2KO (B; −/−) slices to which 5 Hz priming stimuli had previously been applied in the presence of 1 mM extracellular Mg²⁺ and 3 mM extracellular Ca²⁺. Scale bars: A: 0.4 mV, 10 ms; B: 0.2 mV, 10 ms.