The coupling of Akt to mTOR is conditional and enabled by weak HFS in the presence of isoproterenol. A, Isoproterenol alone (ISO), but not weak HFS alone, increased the phosphorylation of ERK at T202/Y204 in area CA1. A similar level of ERK phosphorylation was produced by the combined ISO-wHFS protocol (compare lanes 2 and 4). All group n values ≥6. The asterisks, here and unless otherwise noted, indicate significant differences (p <0.05) from control slices that received only test stimuli. B, Isoproterenol alone increased Akt phosphorylation at T308 to the same extent as ISO-wHFS (compare lanes 2 and 4), while weak HFS alone had no effect. The phosphorylation of Akt induced by ISO-wHFS was completely blocked by U0126 (20 μm). All group n values ≥6. C, Isoproterenol alone did not increase p70S6K phosphorylation (at T389) or eEF1A expression above their basal levels (p values > 0.05). However, both measures were significantly increased by ISO-wHFS, and these effects were prevented by incubation with U0126 (20 μm). All group n values ≥8. D, ISO-wHFS increased immunoreactivity for phospho-p70S6K in the apical dendrites and cell bodies of CA1 pyramidal cells. Images are representative of three experiments, with little or no effect of isoproterenol or weak HFS alone. Scale bar, 100 μm.