Fig. 3

AMPAR-mediated excitatory synaptic transmission and long-term synaptic plasticity in CA1 hippocampal neurons. a Averaged traces of AMPA evoked EPSCs at − 70 and + 40 mV in WT and GluA2^+/ECS(G) mice. b Current-voltage (I/V) relationship of synaptic responses at − 70, 0 and + 40 mV in WT and GluA2^+/ECS(G) mice (n=10 GluA2^+/ECS(G) and 15 WT cells, normalized to evoked EPSC amplitude at − 70 mV; t-test). c Time plot of evoked EPSC amplitude in the presence of the Ca²⁺-permeable AMPAR antagonist, Naspm (50 μM, n=7 GluA2^+/ECS(G) and 8 WT cells), normalized to the pre-Naspm baseline. Inset: Representative current traces of AMPA EPSCs (recorded at − 70 mV) before and during application of Naspm in WT and GluA2^+/ECS(G) mice. HFS induced LTP of fEPSPs in the hippocampal CA1 region of GluA2^+/ECS(G) and WT mice, in (d) control ACSF (n=5 GluA2^+/ECS(G) and 7 WT slices; t-test), and in the presence of (e) the NMDA receptor antagonist DL-AP5 (100 μM; n=7 GluA2^+/ECS(G) and 6 WT slices; t-test), or (f) DL-AP5 plus the Ca²⁺-permeable AMPAR antagonist IEM1460 (50 μM; n=5 GluA2^+/ECS(G) and 6 WT slices; t-test). In (d – f) fEPSP slope is normalized over 20 min prior to HFS. g Kainate induced Co²⁺ loading in the hippocampus revealed Co²⁺ uptake in the CA1 cell layer of GluA2^+/ECS(G) mice. h The AMPA and Kainate receptor antagonist NBQX (20 μM), and the non-competitive AMPAR antagonist GYKI 52466 (100 μM) sufficiently blocked Co²⁺ update in the CA1