The effect of the pro-inflammatory cytokine, interleukin-1beta on an NMDA receptor-independent form of synaptic plasticity brought about by the application of the K+ channel blocker tetraethylammonium, was examined in the rat dentate gyrus in vitro. Field excitatory postsynaptic potentials (EPSPs) were recorded from the medial perforant path of the dentate gyrus every 20 s. Perfusion of the K+ channel blocker, tetraethylammonium chloride (25 mM) for 10 min and subsequent washout gave rise to robust and long-term potentiation of the field EPSP slope (tetraethylammonium induced long-term potentiation; 125+/-5% of baseline 60 min following tetraethlylammonium-washout; n = 7, P < 0.05) Application of interleukin-1beta (1 ng/ml) for 30 min was found to inhibit the induction, but not the maintenance of the tetraethylammonium induced long-term potentiation (n = 8). Heat denatured interleukin-1beta had no effect on tetraethylammonium induced long-term potentiation (n = 6). The expression of tetraethylammonium induced long-term potentiation was found to be accompanied by an increase in the magnitude of paired pulse depression seen at interstimulus intervals of 20 and 100 ms (controls, 42+/-5% and 13+/-2%; tetraethylammonium, 62+/-5% and 22+/-2% respectively for both intervals; n = 6, P < 0.05). The increase in paired pulse depression at an interstimulus interval of 100 ms was significantly attenuated by pre-treatment of slices with interleukin-1beta. The inhibitory effect of interleukin-1beta on both tetraethylammonium induced long-term potentiation and the tetraethylammonium induced increase in paired pulse depression was antagonised by pre-incubation with the interleukin-1 receptor antagonist. Interleukin-1 receptor antagonist was found to have no effect on tetraethylammonium induced long-term potentiation when applied on its own (n = 5). The p38 mitogen activated protein kinase inhibitor SB203580 (4-(4-fluorophenyl)-2-(4 methylesulfinylphenyl)-5-(4-pyridyl)1H-imidazole) was also found to inhibit the induction of tetraethylammonium induced long-term potentiation (n = 6). These findings suggest a possible role for interleukin-1beta in the modulation of NMDA receptor-independent synaptic plasticity in the rat dentate gyrus.
Animals Dentate Gyrus