Ai-Di, Plots of pooled and normalized data illustrating the effects of leptin on excitatory synaptic transmission in the presence of either the ERK inhibitor, U0126 (filled circle) or the PI 3-kinase inhibitor, wortmannin (open circle) at P5-8 (Ai), P11-18 (Bi), 12-16 weeks (Ci) and 12-14 months (Di) of age, respectively. Aii-Dii, Histograms of the pooled data showing the relative effects of leptin on synaptic transmission in control conditions and in the presence of either LY294002 (10 μM), wortmannin (50 nM), U0126 (20 μM) or PD98059 (20 μM). Both the leptin-induced LTD at P5-8 and the transient synaptic depression at P11-18 are mediated by an ERK-dependent process as inhibition of ERK activation prevented the effects of leptin. Conversely, the ability of leptin to increase synaptic transmission at 12-16 week (C) or 12-14 month (D) involved a PI 3-kinase-dependent process as inhibition of PI 3-kinase signalling completely inhibited the effects of leptin.