Functional integrity of NMDA-dependent LTP induction mechanisms across the lifespan of F-344 rats.

Abstract

Previous studies have reported a lack of an age effect in the induction of long-term potentiation (LTP) at CA1 synapses, using robust (supramaximal) stimulation parameters, but an apparent age effect on the induction threshold of LTP using less robust stimulation, in the perithreshold region. These findings have led to the suggestion that old animals may experience an alteration either in the efficacy of activation of 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 animals is that, because of the known reduction of the intracellularly recorded, compound EPSP magnitude in old rats, equivalent electrical stimulation results in a smaller effective depolarization of the postsynaptic cells and a consequently less effective activation of NMDA receptors, which are otherwise functionally normal. To distinguish between these two hypotheses, weak orthodromic stimulation was paired with intracellularly applied current pulses, thus holding constant the degree of postsynaptic depolarization. No differences in LTP induction threshold or magnitude were observed in a large sample of rats from three age groups. It is concluded that the NMDA receptor mechanisms and associated biochemical processes leading to LTP induction are not altered in aged F-344 rats. The reduced compound EPSP in old animals was reconfirmed in the present study, and a significant correlation was found in old rats between the magnitude of the EPSP at a fixed stimulus level and their performance on a spatial memory task.