Altered synaptic plasticity in GluN2D KOs.
(A) Pooled data showing the time course of potentiation of fEPSPs (mean ± SEM) for WTs (filled circles, n = 21) and KOs (open circles, n = 17). Decay of STP was fitted using a bi-exponential decay function (black curve fits WT and grey curve fits KO). The rate of decay of STP1 and STP2 were not significantly different between WTs (τ1 = 3.0 min, τ2 = 24.0 min) and KOs (τ1 = 4.7 min, τ2 = 25.8 min) (τ1 F(1, 3333) = 1.231, p = 0.267, τ2 F(1, 3333) = 0.0801, p = 0.777, F test). In this and subsequent time course plots, the arrowhead indicates the time of high frequency stimulation and the associated “B” refers to the number of bursts delivered. Representative fEPSPs from WTs and KOs at the time-points indicated in A are shown on the right. (B) The level of STP1 and STP2 were calculated by integrating the fast and slow components of the bi-exponential decay function, respectively, and are presented normalised with respect to the corresponding control. STP1 was significantly lower in WTs (100.0 ± 10.1%) compared to KOs (212.4 ± 19.4%; ****p < 0.0001, t(36) = 5.431, t-test). STP2 was not significantly different between WTs (100.0 ± 13.0%) and KOs (138.7 ± 15.7%; p = 0.0633, t(36) = 1.916, t-test). LTP in WTs (38.5 ± 4.3%) was significantly less than in KOs (52.5 ± 5.5%; t(36) = 2.055, *p = 0.0472, t-test) (C) Time course of potentiation in WTs (filled circles, n = 4) and KOs (open circles, n = 5) in the presence of GABAA and GABAB receptor antagonists. Decay time constant of STP1 and STP2 were not different between WTs (τ1 = 1.7 min, τ2 = 19.2 min) and KOs (τ1 = 2.1 min, τ2 = 25.1 min; τ1 F(1, 796) = 1.081, p = 0.299; τ2 F(1, 796) = 1.172, p = 0.279, F test). In this and subsequent figures, horizontal bars on the time course plots indicates the duration of compound application. (D) STP1 level was significantly lower in WT (100 ± 8.8%) compared to KOs (191.6 ± 32.2%; *p = 0.0437, t(7) = 2.456, t-test). STP2 was significantly greater in WTs (100 ± 13.4%) compared to KOs (45.5 ± 14.5%; *p = 0.0309, t(7) = 2.694, t-test). LTP was similar in WTs (79.4 ± 8.1%) and KOs (67.4 ± 10.7%; t(7) = 0.8548, p = 0.421; t-test).