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 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 microg/ml, respectively. Lipid A (1 microg/ml), the biologically active component of lipopolysaccharide, mimicked the effects of 10 microg/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 microg/ml lipopolysaccharide. The NMDA receptor antagonist D,L-2-amino-5-phosphonovaleric acid (APV, 50 microM), nifedipine (10 microM) or lipopolysaccharide (10 or 50 microg/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.
Jo
J H
JH
Department of Biology, Inha University, Inchon 402-751, South Korea.
Park
E J
EJ
Lee
J K
JK
Jung
M W
MW
Lee
C J
CJ
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013569:Synapses / Q000187:drug effects; D013997:Time Factors
D002121:Calcium Channel Blockers; D008070:Lipopolysaccharides; D016194:Receptors, N-Methyl-D-Aspartate; D009543:Nifedipine; D002118:Calcium