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

Abstract

We examined the effects of lipopolysaccharide, a bacterial endotoxin, on synaptic plasticity in the rat hippocampal CA1 area in vitro. Lipopolysaccharide 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 μg/ml, respectively. Lipid A (1 μg/ml), the biologically active component of lipopolysaccharide, mimicked the effects of 10 μg/ml lipopolysaccharide on long-term potentiation and depression. Nifedipine, an L-type voltage-sensitive Ca 2+ channel antagonist, did not influence the induction of long-term potentiation and depression, whereas a high concentration of extracellular calcium enabled long-term potentiation induction in the presence of 10 μg/ml lipopolysaccharide. The NMDA receptor antagonist d, l-2-amino-5-phosphonovaleric acid (APV, 50 μM), nifedipine (10 μM) or lipopolysaccharide (10 or 50 μg/ml) partially reduced the magnitude of tetraethylammonium-induced long-term potentiation. Nifedipine combined with lipopolysaccharide completely blocked tetraethylammonium-induced long-term potentiation. Whole-cell voltage clamp recordings showed that lipopolysaccharide suppressed NMDA receptor-mediated excitatory postsynaptic currents (EPSCs). Our results indicate that lipopolysaccharide acutely modifies synaptic plasticity by blocking Ca 2+ entry through NMDA receptors, suggesting a possible mechanism for the amnesic action of bacterial infection.