FUNCTIONAL INTEGRITY OF NMDA-DEPENDENT LTP INDUCTION MECHANISMS ACROSS THE LIFE-SPAN OF F344 RATS

Previous studies have reported a lack of an age effect in the inductio n of long-term potentiation (LTP) at CA1 synapses, using robust (supra maximal) stimulation parameters, but an apparent age effect on the ind uction threshold of LTP using less robust stimulation, in the perithre shold region. These findings have led to the suggestion that old anima ls may experience an alteration either in the efficacy of activation o f N-methyl-D-aspartate (NMDA) receptors or in the metabolic processes subsequent to NMDA receptor activation that lead to LTP expression. An alternative explanation for the apparent threshold change in old anim als is that, because of the known reduction of the intracellularly rec orded, compound EPSP magnitude in old rats, equivalent electrical stim ulation results in a smaller effective depolariszation of the postsyna ptic cells and a consequently less effective activation of NMDA recept ors, which are otherwise functionally normal. To distinguish between t hese two hypotheses, weak orthodromic stimulation was paired with intr acellularly applied current pulses, thus holding constant the degree o f postsynaptic depolarization. No differences in LTP induction thresho ld of magnitude were observed in a large sample of rats from three age groups. It is concluded that the NMDA receptor mechanisms and associa ted biochemical processes leading to LTP induction are not altered in aged F-344 rats. The reduced compound EPSP in old animals was reconfir med. in the present study, and a significant correlation was found in old rats between the magnitude of the EPSP at a fixed stimulus level a nd their performance on a spatial memory task.