Interleukin-1 beta inhibits a tetraethylammonium-induced synaptic potentiation in the rat dentate gyrus in vitro

The effect of the pro-inflammatory cytokine, interleukin-1 beta on an NMDA receptor-independent form of synaptic plasticity brought about by the appli cation of the K+ channel blocker tetraethylammonium, was examined in the ra t 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 potent iation of the field EPSP slope (tetraethylammonium induced long-term potent iation; 125 +/- 5% of baseline 60 min following tetraethylammonium-washout; n = 7, P < 0.05) Application of interleukin-1 beta (1 ng/ml) for 30 min wa s found to inhibit the induction, but not the maintenance of the tetraethyl ammonium induced long-term potentiation (n = 8). Heat denatured interleukin -1 beta had no effect on tetraethylammonium induced long-term potentiation (n = 6). The expression of tetraethylammonium induced long-term potentiatio n was found to be accompanied by an increase in the magnitude of paired pul se depression seen at interstimulus intervals of 20 and 100 ms (controls, 4 2 +/- 5% and 13 +/- 2%; tetraethylammonium, 62 +/- 5% and 22 +/- 2% respect ively for both intervals; It = 6, P < 0.05). The increase in paired pulse d epression at an interstimulus interval of 100 ms was significantly attenuat ed by pre-treatment of slices with interleukin-1 beta. The inhibitory effec t of interleukin-1 beta on both tetraethylammonium induced long-term potent iation and the tetraethylammonium induced increase in paired pulse depressi on was antagonised by pre-incubation with the interleukin-1 receptor antago nist. Interleukin-1 receptor antagonist was found to have no effect on tetr aethylammonium induced long-term potentiation when applied on its ou n (n = 5). The p38 mitogen activated protein kinase inhibitor SB203580 (4-(4-fluo rophenyl)-2-(4 methylesulfinylphenyl)-5-(4-pyridyl)1H-imidazole) was also f ound to inhibit the induction of tetraethylammonium induced long-term poten tiation (n = 6). These findings suggest a possible role for interleukin-1 b eta in the modulation of Nh IDA receptor-independent synaptic plasticity in the rat dentate gyrus. (C) 1999 Elsevier Science B.V. All rights reserved.