Lipopolysaccharide inhibits induction of long-term potentiation and depression in the rat hippocampal CA1 area

We examined the effects of lipopolysaccharide, a bacterial endotoxin, on sy naptic plasticity in the rat hippocampal CAL area in vitro. Lipopolysacchar ide suppressed the induction of long-term potentiation elicited by tetanic stimulation and long-term depression. elicited by low-frequency stimulation of Schaffer collateral-commissural fibres at 10 and 50 (mug/ml, respective ly. Lipid A (1 mug/ml), the biologically active component of lipopolysaccha ride, mimicked the effects of 10 mug/ml lipopolysaccharide on long-term pot entiation and depression. Nifedipine, an L-type voltage-sensitive Ca2+ chan nel antagonist, did not influence the induction of long-term potentiation a nd depression, whereas a high concentration of extracellular calcium enable d long-term potentiation induction in the presence of 10 mug/ml lipopolysac charide. The NMDA receptor antagonist D,L-2-amino-5-phosphonovaleric acid (APV, 50 m uM), nifedipine (10 muM) or lipopolysaccharide (10 or 50 mug/ml) partially reduced the magnitude of tetraethylammonium-induced long-term potentiation. Nifedipine combined with lipopolysaccharide completely blocked tetraethyla mmonium-induced long-term potentiation. Whole-cell voltage clamp recordings showed that lipopolysaccharide suppressed NMDA receptor-mediated excitator y postsynaptic currents (EPSCs). Our results indicate that lipopolysacchari de acutely modifies synaptic plasticity by blocking Ca2+ entry through NMDA receptors, suggesting a possible mechanism for the amnesic action of bacte rial infection. (C) 2001 Published by Elsevier Science B.V.