BETA-AMYLOID SELECTIVELY AUGMENTS NMDA RECEPTOR-MEDIATED SYNAPTIC TRANSMISSION IN RAT HIPPOCAMPUS

THE effect of beta-amyloid on lpha-amino-3-hydroxy-5-methyl-4-isoxazol epropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediat ed glutamatergic excitatory postsynaptic currents measured with whole- cell voltage-clamp techniques, was investigated in the rat dentate gyr us in vitro. Application of beta-amyloid (1-40) by extracellular perfu sion (200nM) or intracellularly via the recording pipette (100nM) resu lted in a gradual enhancement of the NMDA receptor-mediated synaptic c urrents which did not reverse on washout. Basal AMPA receptor-mediated transmission, resting membrane potential or input resistance of the g ranule cells did not change. These results provide direct evidence tha t beta-amyloid selectively interacts with the potentially neurotoxic N MDA receptor via a postsynaptic site. It is proposed that this action may help explain the synaptic changes seen in Alzheimer's disease.