Aging Differentially Alters Forms of Long-Term Potentiation in Rat Hippocampal Area CA1

Abstract

Shankar, Subbakrishna, Timothy J. Teyler, and Norman Robbins. Aging differentially alters forms of long-term potentiation in rat hippocampal area CA1. J. Neurophysiol. 79: 334–341, 1998. Long-term potentiation (LTP) of the Schaffer collateral/commissural inputs to CA1 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) were recorded extracellularly from stratum radiatum before and after a tetanic stimulus consisting of four 200-Hz, 0.5-s trains given 5 s apart. Under control conditions, a compound LTP consisting of both forms was induced and was similar, in both time course and magnitude, in young and old animals. NMDAR-dependent LTP (nmdaLTP), isolated by the application of 10 μM nifedipine (a voltage-dependent calcium channel blocker), was significantly reduced in magnitude in aged animals. The VDCC dependent form (vdccLTP), isolated by the application of 50 μM d,l-2-amino-5-phosphonvalerate (APV), was significantly larger in aged animals. Although both LTP forms reached stable values 40–60 min posttetanus 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 kinase inhibitor) together blocked potentiation. These results suggest that aging causes a shift in synaptic plasticity from NMDAR-dependent mechanisms to VDCC-dependent mechanisms. The data are consistent with previous findings of increased L-type calcium current and decreased NMDAR number in aged CA1 cells and may help explain age-related deficits in learning and memory.