BETA-AMYLOID PRODUCES A DELAYED NMDA RECEPTOR-DEPENDENT REDUCTION IN SYNAPTIC TRANSMISSION IN RAT HIPPOCAMPUS

THE delayed effect of in vivo injection of beta-amyloid on glutamaterg ic synaptic transmission was investigated in the rat hippocampus. The amplitude of field excitatory postsynaptic potentials recorded in the CA1 region of awake rats was reduced 24 h after the injection of beta- amyloid (1-40) (0.4 or 3.5 nmol i.c.v.). The effect lasted for at leas t 5 days and was prevented by treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist CPP (7 mg kg(-1) x 2, i.p.). Similar result s were obtained ex vivo in the dentate gyrus. There was no change in t he ability to induce long-term potentiation. These results provide dir ect evidence that beta-amyloid produced a delayed reduction in the fun ction of glutamatergic synapses, probably as a result of an initial ov er-activation of the NMDA receptor-mediated component of transmission.