Leptin inhibits 4-aminopyridine– and pentylenetetrazole-induced seizures and AMPAR-mediated synaptic transmission in rodents
J. Clin. Invest. Lin Xu, et al. 118:272 doi:10.1172/JCI33009 [Go to this article.]

Figure 4
Leptin selectively inhibits the AMPAR-mediated component of the CA1 field excitatory postsynaptic potentials (fEPSPs) in mouse hippocampal slices. (A) Leptin inhibited the AMPAR component of the CA1 fEPSP. Time course of the fEPSP slope for the AMPAR component after bath-applied 0.6 nM leptin as indicated by the bar (n = 4 slices, 2 mice). The AMPAR component was isolated by adding the N-methyl-d-aspartate (NMDA) antagonist D-APV (50 μM) as indicated by the bar. (B) In contrast, leptin did not inhibit the NMDAR component of the CA1 fEPSP. Time course of the fEPSP slope for the NMDA component after bath-applied 0.6 nM leptin as indicated by the bar (n = 6 slices, 4 mice). The NMDAR component was isolated by adding the AMPAR antagonist CNQX (10 μM) in Mg²⁺-free ACSF. Data in A and B were analyzed as in Figure 3B. The bars indicate when Mg²⁺-free ACSF and leptin were applied. (C and D) Leptin enhances paired-pulse facilitation. (C) Superimposed representative pairs of CA1 fEPSPs from the same slice demonstrate fEPSP inhibition and increased paired pulse facilitation in 0.6 nM leptin (arrows). Interstimulus interval: 25 ms; calibration: 4 ms, 0.2 mV. (D) Cumulative data from 5 slices (5 mice) comparing the paired pulse facilitation ratio (PPF = P2/P1, where P1 is the slope of the first fEPSP and P2 is the slope of the second fEPSP) before and after the application of 0.6 nM leptin for 20 minutes (*P < 0.02, paired t test).