Figure 4.

Peripheral inflammation induces the insertion of GluR2-lacking AMPA receptors to the synapse. A, Sample EPSC recordings of stimulation of the Schaffer collateral at different holding potentials (−60 to +60 mV) from the pyramidal neurons in the CA1 area of hippocampus from saline- and TNBS-treated rats at day 4 after the induction of bowel inflammation by TNBS. Each trace represents the average of five traces. B, C, Significant AMPA current rectification is observed in TNBS-treated neurons (saline, n = 11 cells, 7 rats; TNBS, n = 13 cells, 7 rats). The RI (defined as the ratio of eEPSC amplitude at +40 mV to that at −60mV) was significantly decreased in neurons from TNBS-treated animals. Data are presented as mean ± SEM. **p = 0.0044 (t test). D, Sample traces of evoked EPSCs from stimulation of the Schaffer collateral, recorded from the CA1 area of hippocampus before (black) and after (gray) the perfusion of the GluR2-lacking AMPA receptor antagonist NASPM (100 μm). Currents were recorded at −60 mV, and the peak amplitudes were measured. Each representative trace is an average of at least 10 traces. E, The effect of NASPM was calculated and presented as the percentage decline in the current. A significant increase was observed in the effect of NASPM in TNBS-treated rats compared to controls that would translate into increased postsynaptic insertion of the GluR2-lacking AMPA receptor in TNBS-treated animals. Data represent the mean ± SEM (saline, n = 7 cells, 4 rats; TNBS, n = 8 cells, 4 rats). **p = 0.0026 (t test). F, There were decreased mRNA levels of the GluR2 subunit in the CA1 area of hippocampus in the animals with peripheral inflammation compared with controls (saline, n = 5; TNBS, n = 5; t test, t = 3.6547, *p = 0.0065). G, There was significantly less GluR2 protein expression in the CA1 area of hippocampus in the animals with peripheral inflammation compared to controls (Mann–Whitney U test, z = −2.008, *p = 0.045; saline, n = 5; TNBS, n = 6). Calibrations: A, D, 20 ms, 200 pA.