(a,c) Puromycin labeling of newly synthesized proteins showed that four trains of HFS in area CA1 to induce L-LTP results in increased protein synthesis levels compared with no stimulation (Ctrl) in WT hippocampal slices (t(14)= −3.52, p=0.005), while stimulated Akt1 KO slices fail to increase protein synthesis from unstimulated levels (t(14)=-1.45, p=0.167). GAPDH, loading control. (b,d) Akt3 KO hippocampal slices showed a normal increase in protein synthesis after four trains of HFS (Akt3 WT Ctrl vs. HFS t(12)=-2.75, p=0.018; Akt3 KO Ctrl vs. HFS t = −2.20, p=0.047). GAPDH, loading control. (e,g) Akt1 KO slices failed to show an increase in S6 phosphorylation (pS6 S235/236) normalized to total S6 (totS6) levels after tetanic stimulation (Akt1 WT Ctrl vs. HFS t(14)=-2.71, p=0.016; Akt1 KO Ctrl vs. HFS t(14)=-1.01, p=0.33). (f,h) Akt3 KO slices showed a normal increase in pS6 S235/236 levels after tetanic stimulation (Akt3 WT Ctrl vs. HFS t(14)=-2.92, p=0.01, Akt3 KO Ctrl vs. HFS t(14)=-2.59, p=0.02). n= 7–11 slices/group, 4–6 mice/group, *p<0.05.