AGING DIFFERENTIALLY ALTERS FORMS OF LONG-TERM POTENTIATION IN RAT HIPPOCAMPAL AREA CA1

Aging differentially alters forms of long-term potentiation in rat hip pocampal area CAl. J. Neurophysiol. 79: 334-341, 1998. Long-term poten tiation (LTP) of the Schaffer collateral/commissural inputs to CAI in the hippocampus was shown to consist of N-methyl-D-aspartate receptor (NMDAR) and voltage-dependent calcium channel (VDCC) dependent forms. In this study, the relative contributions of these two forms of LTP in in vitro hippocampal slices from young (2 mo) and old (24 mo) Fischer 344 rats were examined. Excitatory postsynaptic potentials (EPSP) wer e recorded extracellularly from stratum radiat-um before and after II tetanic stimulus consisting of four 200-Hz, 0.5-s trains given 5 s apa rt. Under control conditions, a compound LTP consisting of both forms was induced and was similar, in both time course and magnitude, in you ng and old animals. NMDAR-dependent LTP (nmdaLTP), isolated by the app lication of 10 mu M nifedipine (a voltage-dependent calcium channel bl ocker), was significantly reduced in magnitude in aged animals. The VD CC dependent form (vdccLTP), isolated by the application of 50 mu M D, L-2-amino-5-phosphonvalerate (APV), was significantly larger in aged a nimals. Although both LTP forms reached stable values 40-60 min postte tanus in young animals, in aged animals vdccLTP increased and nmdaLTP decreased during this time. In both young and old animals, the sum of the two isolated LTP forms approximated the magnitude of the compound LTP, and application of APV and nifedipine or genestein (a tyrosine ki nase inhibitor) together blocked potentiation. These results suggest t hat aging causes a shift in synaptic plasticity from NMDAR-dependent m echanisms to VDCC-dependent mechanisms. The data are consistent with p revious findings of increased L-type calcium current and decreased NMD AR number In aged CAI cells and may help explain age-related deficits in learning and memory.