File:Lu Nicoll 2009 FIG6.jpg

Figure 6.

Analysis of Extrasynaptic AMPARs (A) Sample traces of AMPAR currents from OOPs from uninfected control (black) and Cre (green) cells from CA1 pyramidal neurons from various genetic backgrounds. Scale bar, 200 pA, 1 s. The recordings were made from acute hippocampal slices (P13–P17 for ΔGluA2 and P20–P28 for all other genetic backgrounds) from animals injected at P0–P2. (B) I/V curves of AMPAR currents from OOPs. Control, black; Cre, green. Deletion of the GluA2 subunit, but not other subunits, caused strong inward rectification of the evoked current. Bar graph at the bottom shows the RI for each condition (Cnt, 0.85 ± 0.02, n = 8; ΔGluA1, 0.81 ± 0.04, n = 5; p = 0.39; ΔGluA2, 0.09 ± 0.01, n = 6; ∗p < 0.001; ΔGluA3, 0.80 ± 0.03, n = 5; p = 0.22; ΔGluA2A3, 0.10 ± 0.02, n = 6; ∗p < 0.001; ΔGluA1A2, 0.15 ± 0.03, n = 5; ∗p < 0.001). (C) Summary bar graph shows consequences of deletion of respective genes on AMPAR current from OOPs (Cnt, −648.7 ± 45.2 pA, n = 23; ΔGluA1, −35.3 ± 13.1 pA, n = 16, ∗p < 0.001; ΔGluA2, −684.3 ± 92.2 pA, n = 11, p = 0.70; ΔGluA3, −674.2 ± 63.5 pA, n = 13, p = 0.74; ΔGluA2A3, −656.8 ± 76.3 pA, n = 14, p = 0.92; ΔGluA1A3, −2.5 ± 1.0 pA, n = 14, ∗p < 0.001; ΔGluA1A2, −24.1 ± 5.2 pA, n = 25, ∗p < 0.001; ΔGluA1A2A3, −1.01 ± 0.65 pA, n = 8, ∗p < 0.001). (D) Summary bar graph shows consequences of deletion of respective genes on AMPAR EPSCs (percent control: ΔGluA1, 19.4 ± 3.1%, n = 31, ∗p < 0.001; ΔGluA2, 51.7 ± 3.8%, n = 86, ∗p < 0.001; ΔGluA3, 83.8 ± 1.0%, n = 19, ∗p < 0.05; ΔGluA2A3, 42.8 ± 5.2%, n = 14, ∗p < 0.001; ΔGluA1A3, 12.1 ± 2.4%, n = 12, ∗p < 0.001; ΔGluA1A2, 5.7 ± 1.4%, n = 24, ∗p < 0.001; ΔGluA1A2A3, 2.4 ± 0.6%, n = 13, ∗p < 0.001). (E) Models for AMPAR compositions at synaptic and extrasynaptic membranes. At CA1 pyramidal neurons, ∼80% synaptic AMPARs are GluA1A2 heteromers, and ∼16% synaptic AMPARs are GluA2A3 heteromers. On the other hand, ∼95% extrasynaptic AMPARs are GluA1A2 heteromers.