NMDA receptor activation in the aged rat hippocampus

Age-related alterations of N-methyl-D-aspartate receptor (NMDAr) activation were investigated in the CA1 held of hippocampal slices from young (3-6 mo nths old) and aged (25-33 months old) Sprague-Dawley rats by using ex vivo extracellular electrophysiological recording techniques. NMDAr-mediated fie ld excitatory postsynaptic potentials (fEPSPs) were induced by electrical s timulation of glutamatergic fibers in a magnesium (Mg2+)-free medium supple mented with the non-NMDAr antagonist CNQX. The fEPSPs were significantly sm aller in aged rats, whereas the response of presynaptic afferent fibers rem ained unaffected. No significant age-related differences were found in the ability of Mg2+ to depress the magnitude of NMDAr-mediated fEPSPs. The resp onsiveness of postsynaptic NMDAr to the agonist was assessed in both groups of animals. No age-related differences were recorded either in the depolar izing effect of bath-applied NMDA or in the magnitude of the depolarization after altering extracellular Mg2+ concentration. Finally, shortterm potent iation (STP) of excitatory transmission was studied in young and aged rats considering the pivotal role of NMDAr in synaptic plasticity. No age-relate d alterations of the magnitude and the time course of STP in response to 10 or 30 Hz conditioning stimulation were found. Because of the decrease in t he magnitude of NMDAr-mediated synaptic transmission in aged animals, the a bsence of obvious modifications of synaptic plasticity suggests the occurre nce of compensatory mechanisms that are discussed. (C) 2000 Elsevier Scienc e Inc. All rights reserved.